Journal articles on the topic 'Global jazz'

This article addresses one of the manifestations of interaction between different music domains, using the sphere of jazz as an example. In the course of evolution, the art of music has developed five relatively independent domains based on fundamentally different principles of musical thought. Globalization, which has intensified in the 20th century and continues to grow in the 21st, gave birth to a new domain called by us “unionique music”. This domain is the object of our research. The relevance of this study stems from the fact that unionique music compositions do not fit the standard principles of genre classifications used by academic music scholars. At the same time, an important feature that unites these compositions is the combination of such spheres of music as jazz, rock, “traditional” music of Western European academic tradition, ethnic music and folklore. Nevertheless, the degree of impact of a particular music domain in different compositions has different indicators. This article focuses on the analysis of unionique music compositions that contain expressive means of various domains, but at the same time are founded on the jazz-based principle of music playing.

I consider the current state of jazz in South Africa in response to the formation of the nation-state in the 1990s. I argue that while there is a recurring sense of the precarity of jazz in South Africa as measured by the short lives of jazz venues, there is nevertheless a vibrant jazz culture in which musicians are using their own studios to experiment with new ways of being South African through the freedom of association of people and styles forming a music that sounds both local and comfortable in its sense of place in the global community. This essay uses the words of several South African musicians and concludes by situating the artistic process of South African artist William Kentridge in parallel to jazz improvisation.

Jazz, today a broadly defined, global form of improvised music, remains a music between heaven and earth, with its roots in both nightclubs and churches. Jazz can be dance music, as well as music that triggers emotions, memories, and subjective images. It can also lead to experiences of transcendence. In which ways, though, do jazz artists connect their spiritual and religious experiences and beliefs with their individual musical language? In contrast to Western, composed sacred music, jazz generates religious meaning through its improvisatory practices, which unfold differently in each performance, depending on the performers, listeners, and performance spaces. Often, jazz musicians feel the poetic quality of their music to reside in the ambiguity and “fragile” religiosity of their music. This article discusses from a historical and contemporary perspective the “fragilization” processes at work in religiously inspired jazz. It distinguishes different levels of religious meaning, purpose, and spiritual experience. In so doing, it explores productive resonances between the characteristics of jazz and Paul Corrigan’s definition of “postsecular” American poetry written in the late twentieth and early twenty-first centuries.

The focus of this study is the melodic motive. It uses a tool called the Ordered Step Motive (OSM) to investigate the way linear motives give shape to jazz compositions that have frequently changing tonal centers, nonfunctional chord connections, no clear global tonics, or structurally open, circular forms. This study contributes to the written body of theoretical knowledge about jazz composition by engaging with current scholarship on tonal ambiguity, circular form, and motivic associations between melody and harmonic organization. This study also invites further research into the relationship between common riffs and underlying structure in jazz composition, which may reveal crucial differences between standards written by Broadway and Tin-Pan-Alley composers and those written by practicing jazz musicians.

AbstractThis study aims to make the contemporary Hungarian jazz field the focus of a sociological investigation, based on a critical reinterpretation of Bourdieu's relational theory of artistic fields. It aims to grasp the logic of symbolic distinctions by analysing the free/mainstream dichotomy. This dichotomy of historically constituted poles is understood as a system of structuring oppositions that play a decisive role in the position-takings and prestige-construction of jazz musicians. The analysis of qualitative data shows how different evaluations and interpretations of shared musical references are instrumentalised in order to occupy positions in the field. Further, this article argues that such a qualitative analysis of local jazz fields transcends the national context, since culturally hybrid jazz diasporas offer an excellent terrain for analysing how the circulation of transnational artistic references influences the cultural dynamism of local fields that are embedded within global networks of cultural production.

Swing refers to a characteristic long-short subdivision of the beat that is generally considered a crucial aspect that contributes to the quality of a jazz or pop performance. The current study measures this pattern (referred to as the 'swing ratio') at different tempi in jazz drumming. The experimental setup differs from earlier studies in a number of ways. First, swing ratios were systematically measured at different beat durations in a musically realistic range. Second, repeated performances were collected to check for consistency. Third, drummers were asked to perform on a full MIDI drum kit. The results show that professional jazz drummers have enormous control over their timing. Nevertheless, the swing ratio is not kept constant, but it is systematically adapted to a global tempo. As such, this study provides further support for the hypothesis that expressive timing generally does not scale with tempo.

Over the past two decades the topic of graduate outcomes has increasingly informed the discourse on the changing nature of universities. For conservatoires and university music departments the global shift in audience demand away from western classical music and jazz styles (traditionally the cornerstone tertiary music programs) to contemporary commercial music (CCM) has added an extra dimension to the graduate outcomes discussion with respect to vocation preparation and musicians’ portfolio careers. Few studies have tracked the career paths of music graduates across time with none focused on jazz/contemporary singers. This report discusses the findings from a snapshot study of Jazz/Contemporary Voice graduates (2001 to 2012) of one Australian conservatoire. The purpose of this research was to better describe this population of graduates in terms of employment outcomes, the dynamics of their employment activities, employment-seeking strategies and the relevance of university coursework to their employability. Their responses have implications for tertiary music training programs.

AbstractA small basement in Manhattan's Greenwich Village neighborhood, an area known for its bohemian values, is home to what is now one of jazz's oldest and most significant venues, the Village Vanguard. Although its very name, geography, and twentieth-century countercultural context define the Village Vanguard, a haven for experiment, its unequaled historical significance and current status as a major landmark within worldwide jazz culture have led to a twenty-first-century reality in which the club not only features but also plays an important role in defining the music that constitutes the most widely accepted subgenre of contemporary jazz, an improvisatory, small-group tradition rooted in the philosophical and musical heritage of bebop. Through an examination of performances both at the Vanguard and in other contexts by pianist Fred Hersch, a performer regularly featured at the club, this article argues that the cultural role of the Village Vanguard, both in spite of and because of the way its longtime owner Lorraine Gordon retained mid-twentieth-century appearances and practices, has shifted from its former purpose as a space for avant-garde experiments to become a powerful force in defining mainstream jazz. Hersch tailors his performances to suit the culture of the Vanguard at multiple levels, including his choice of personnel and ensemble type, the repertoire he does and does not play there, and the musical details of his improvisatory practices. Due to the venue's fame and prevalence as a recording space, choices like these by Hersch and other musicians shape the music widely understood to be at the center of the “jazz tradition,” marking a shift in the nature of the Vanguard that parallels changes in both its local and global context over the past half century as Greenwich Village has undergone substantial gentrification and jazz has gained an ever-stronger foothold as an institutionally recognized art music.

This article characterizes development trends in jazz piano from its origins in the “third-layer” (Konen, V., 1984) of music (ragtime and other “pre-jazz” forms) to the present time (avant-garde and retro styles of the late 20th – early 21st centuries). Main attention was devoted to the stylistic sphere, which represents an entirety of techniques and methods of jazz piano improvisation and combines genre and style parameters. In this context, the currently available information about jazz pianism and its sources (Kinus,Y., 2008; Stoliar, R., 2017) was reviewed, and sociocultural determinants, which contributed to the advent and changes of jazz piano styles were highlighted. Standing out among them at the first (traditional) stage are the schools and individual creative techniques known under generic name “stride piano” and based on the ragtime technique. At the second (contemporary) stage beginning from bebop, jazz piano stylistics gradually diverge from standardized textural formulas of homophonicharmonic type and attain fundamental diversity depending on creative attitudes of leading jazz pianists. The question of jazz piano stylistics is one of the least studied in jazz theory. The existing works devoted to this subject address mostly the sequence of the advent and changes of jazz piano styles along with the general characteristics of their representatives. Beginning from approximately the 1920s, jazz piano styles appeared and changed so fast that they left no time for their comprehension and perception (Kinus, Y., 2008). Only in the newest stylistics of the period after bebop, which divided the art of jazz into traditional and contemporary stages, did these styles attain a certain shape in new modifications and become the components of a phenomenon defined by the generic notion “jazz pianism”. It was stated that the genesis of this phenomenon is usually seen in the art of ragtime, carried in the United States of the late 19th – early 20th centuries by itinerant pianists. This variety of “third-layer” piano music playing produced a significant impact on the art of jazz in general, which is proved by its reproduction in the Dixieland and New Orleans styles as some of the first examples of jazz improvisation. The stylistics of ragtime influenced the entire first stage of jazz piano, which traces its origins back to approximately the 1910s. It combined mental features and esthetics of two traditions: European and Afro-American, which in the entirety produced the following picture: 1) popular and concert area of music playing; 2) gravitation toward demonstration of virtuosic play; 3) domination of comic esthetics; 4) objectivity of expression; 5) tendency toward the completeness of form; 6) inclination toward stage representation. In technological (texturalpianistic) aspect, ragtime, reproduced in the jazz stylistics of stride piano, demonstrated the tendency toward universalization of piano, which combined in the person of one performer the functions of solo and accompaniment, derived from the practice of minstrel banjoists related to the percussion-accented rhythmics of dance accompaniment (Konen, V., 1984). It was stated that ragtime as the transitional bridge to jazz piano existed simultaneously with other forms of “third-layer” music playing found in the Afro-American environment (unlike ragtime itself, which was an art of white musicians). These were semi-folklore styles known as “barrel house” and “honky-tonk(y) piano” cultivated in Wild West saloons. The subsequent development of jazz piano stylistic went along the lines of more vocal and specific directions related mostly to peculiarities of playing technique. Among the more global origins equal in significance to ragtime and stride pianists derivative, blues piano stylistics is worth noting. It represents an instrumental adaptation of vocal blues, which had the decisive influence over the melodics and rhythmics of the right hand party of jazz pianists (ragtime and stride piano highlighted and consolidated the typical texture of accompaniment, i.e., the left hand party). Blues piano style is a multicomponent phenomenon that shaped up as a result of efforts taken by a whole number of jazz pianists. It was developed, and continues to exist until presently, in two variants: a) as a solo piano variant, b) as a duet variant (piano and vocal). Along with blues piano, a style known as “boogie-woogie” was cultivated in jazz piano stylistics of the period before bebop as the new reminiscence of the pre-jazz era (with rock-n-roll becoming a consequence of its actualization in the 1950–1960s). A stylistic genre known as “Harlem piano style” (its prominent representatives include Luckey Roberts, James P. Johnson, Willie “the Lion” Smith, and Thomas “Fats” Waller) became a sort of compendium that combined genetic components of traditional jazz piano. This school has finally defined jazz piano as a form of solo concert music playing, which also determined the subsequent stylistic varieties of this art, the most noteworthy of which are “trumpet piano style”, “swing piano style” and “locked hands style”. Their general feature was interpretation of the instrument as a “small orchestra”, which meant rebirth at the new volute of a historical-stylistic spiral of the “image” of universal piano capable of reproducing the “sounds” of other instruments, voices and their ensembles. Outstanding pianists of various generations have been, and are, the carriers (and often “inventors”) of jazz piano styles. It should suffice to mention the names of such “legends” of jazz as Art Tatum, Oscar Peterson, Thelonious Monk, Bud Powell, Bill Evans, and also Herbie Hancock, Chick Corea, Keith Jarrett (older generation), Gonzalo Rubalcaba, Brad Mehldau, Vadim Neselovskyi, Robert Glasper (middle generation), Eldar Djangirov, Tigran Hamasyan, Cory Henry (younger generation). Conclusions. The description of the stages of development of jazz piano pianism made in this article proves that its polystylistic nature is preserved, and the main representative of certain stylistic inclinations were and remain the texture. Textured formulas serve as the main objects of stylistic interpretations for jazz pianists of different generations. These readings are represented by two vectors – retrospective (revival of jazz traditions) and exploratory, experimental (rapprochement with the academic avant-garde). Of great importance are the styles of personalities, in which polystylistic tendencies are combined with the individual playing manners and improvisation, which, in general, is the most characteristic feature of the current stage of development of jazz piano art.

An interview with Cees J. Hamelink, one of the most important scholars in global communication and international political economy of communication, who was also an active participant in several political initiatives and movements in the field of media and communication, including NWICO and WSIS. We spoke about his political ideas, scholarly work and how his fascinating life-path, which took him to different parts of the world, in many ways had an impact on his intellectual development.

Objectives and methodology. The article is devoted to the revealing of the relation and differences between rock music and jazz, as the phenomena of the “third” layer. It is noted, that, in methodological terms, such a comparative approach is advisable to implement with the use of a paradigm apparatus that fixes a certain commonality in the development of each of the studied phenomena at different stages of evolution. The application of this concept to the phenomena of art is a characteristic feature of modern musicology. In the broadest sense, the paradigm is the possibility of “thinking by analogy” (according to Aristotle), and in music it relates both to the field of theory (views on music as a form of art) and practice (musical and artistic phenomena as the products of composer and performing art).The article proposes a classification of rock music paradigms, which are based on the available data on the aesthetics and communication of jazz and notes that rock music on the path of its evolution has passed a number of stages, which in general can be designated as paradigms. The article suggests a comparative description of the movement of aesthetic and communicative paradigms of jazz and rock music. It is noted that in jazzology this issue has long been relevant, which is not the case for the study of rock music. Despite all the differences in the time of emergence and the nature of evolution, vocabulary and semantics, social functions, jazz and rock have many “common points”. The results of the research. Such features, of jazz and rock music, as improvisational nature, a variety of intonational sources that combine multinational and diverse trends are revealed and systematized as common points. Among the special features are distinguished such as the reliance of jazz mainly on the instrumental and rock music on a mixed vocal and instrumental basis; first is referring to “elitist”, second is referring to “mass”. Various syntheses are also common in jazz and rock music, as well as the correlation of composition and improvisation, performing and authorial principles. It is not so much about mutual influences and syntheses, but about the directions of evolution, the general nature of which is defined as the movement from “realistic” to “phenomenological” (A. Soloviev on the jazz paradigms). At its onset, rock music, like jazz, has been “embedded” in the system of the social and political movement, where its autonomous aesthetic function was not yet identified (youth movements of the 1960s, within which the corresponding “protest music” arose). In the process of mastering vocabulary specific to rock music as a phenomenon of the “third” layer, a new paradigm arose, characterized first as conventionally realistic, and then as conventionally autonomous, where rock music reaches the level of professional art in which laws and rules are established by its representatives themselves (this period begins from the Beatles and will continue further by their followers – “Rolling Stones”, “Led Zeppelin”, “Deep Purple” and other groups). It is noted that “people of rock” as well as “people of jazz” are a special social and communicative community, in which the idea of free communication is the main and determining one, where social, interpersonal, and actually musical factors intertwine. The unifying communicative factor in jazz and rock music is the art of improvisation, in which, in symbiosis, the processes of creating and performing music coexist spontaneously, but are subject to certain paradigm settings. It is emphasized that in the social context, jazz and rock differ in ethnic and age factors, which, however, is eventually overcome in modern global society through consolidation (convergence of African-American and European sources of jazz, transition of rock groups to a more general theme that differs from the original youth focus). It is also noted that rock music, unlike jazz, is too deeply connected with social factors and is always based on topical themes, generalized with varying degrees of artistry. Therefore, its degree of autonomy is much lower than that of elite jazz, which by the last decade of the 20th century had turned into the officially recognized salon art, or into a “conglomerate” consisting of pop elements of various kinds close to the aesthetics of the show industry. It is proved that the differences between jazz and rock music are most clearly manifested at the level of radical-and-phenomenal paradigm, which means plunging into the realm of banal “nothing”, where acts (but actually – does not act) the principle of “no wave” (A. Soloviev about jazz) . While jazz in the post-bop period developed towards elite art under the Free rubric, the extreme expression of which was spontaneous collective “impersonal” (lack of leadership, lack of frontman), the style of rock music developed in a different direction, the vector of which can be considered the opposite of jazz. Firstly, in the field of stylistics and language as its primary carrier, rock music meant a return to improvisational syncretism – a dramatic combination of poetry and music. Secondly, rock music is directly immersed, unlike elite jazz with its style of full linguistic freedom and collage, in the realm of relevant musical and poetic vocabulary, coming not from the rhetorical type of creativity (translating “artificial” into “new artificial”), but from the realities of the set of generally accessible linguistic means, which exists at a given historical moment (and in a certain “geography”). In the conclusions of the article, it is noted that rock music, even in its experimental radical and phenomenological manifestations, associated mainly with the sound realm (electronics, dynamics), remains, as a whole, the phenomenon of pop culture. This does not mean the absorption of rock art by the realm of mass consumerism. The best rock music pieces, which have already become classic, combine in reasonable proportions the “elite” (innovative) and “mass” (traditional), give a special rational embodiment of the idea of combining improvisation and composition – the “cornerstone” in the musical art of the entire “third” layer. The aesthetics and communication of rock music in its latest paradigms are differentiated according to the criteria of various stylistic inclinations – genre, national, regional, personal. Therefore, the study of modern rock music is the task of a number of separate studies devoted to specific issues of the problem, in particular, its main difference from jazz, namely, in the vocal and instrumental nature.

The live music pub and club scene has historically been regarded as the source of a distinctively Australian rock/jazz culture, and the basis for global recording success. This paper examines the history of live venue practices as a case study of a local cultural industry that often existed outside of traditional policy structures and meanings of the arts industries. Confronted with a loss of performance opportunities for local musicians, it is argued that traditional cultural policy mechanisms and platforms used for cultural nationalist outcomes are no longer relevant. Rather, policy intervention must engage with administrative obstacles to live creativity, specifically the series of local regulations that have diminished the viability of live venues. The decline of the rock/jazz pub continues in the face of current federal government support for touring musicians. A closer inspection of the local administration of cultural practice remains the best means of understanding the devaluation of the social and industrial value of live performance.

The article is dedicated to the development of the theatrical amateur performance in Nizhny Tagil in the period, when it was the only one mass phenomenon of the artistic culture in the town. Its main phases — intelligent circle, mass workers theatres, propaganda teams and theatrical jazz — are indicated. Multitasking of the amateur theatre in a small town, its central role in uniting creative people, their enculturation in global cultural process are revealed.

Abstract A single-center trial of CD19 directed, lentiviral transduced chimeric antigen receptor (CAR) T cells (CTL019) for relapsed and refractory (r/r) B-ALL pediatric patients showed rates of CR >90% with prolonged CAR T cell persistence/CR without further therapy in the majority of patients infused (Maude NEJM 2014). We report here the feasibility, safety and efficacy of the first multicenter global pivotal registration CAR T cell trial. Features of this trial include: i) the first trial in which industry-manufactured cells were provided to all patients; ii) enrollment across 25 centers in the US, EU, Canada, Australia, and Japan; iii) successful transfer and manufacturing of cells in a global supply chain; and iv) successful implementation of cytokine release syndrome (CRS) management across a global trial. All patients had CD19 positive B-ALL with morphologic marrow tumor involvement at registration (>5% blasts), and were either primary refractory; chemo-refractory after first relapse, relapsed after second line therapy; or ineligible for allogeneic SCT. CTL019 was manufactured from patient PBMC under GMP conditions in the US, at a centralized "sponsor-owned" manufacturing facility, and supplied to all sites. The primary endpoint of overall remission rate (CR+CRi) within 3 months and secondary endpoints (EFS, DOR, OS and safety) were assessed by an independent review committee. Based on preliminary data as of March 2016, 57 patients were enrolled. There were 3 manufacturing failures (5%), 5 patients were not infused due to death or adverse events (9%), and 15 patients were pending infusion at the data cut off. Following fludarabine/cyclophosphamide lymphodepleting chemotherapy in the majority of the patients, 34 patients (median age 11 [3-23], 50% with prior HSCT) were infused with a single dose of CTL019 at a median dose of 2.9 x106 transduced CTL019 cells/kg (0.2 to 4). Among 29 patients reaching D28 prior to the data cutoff, 83% (24/29) achieved CR or CRi by local investigator assessment, all of which were MRD-negative. Two early deaths occurred prior to initial disease assessment, one due to disease progression and one due to intracranial hemorrhage. Two patients did not respond. One patient was in CR by BM at D28, but CSF was not assessed, therefore this patient was classified as "incomplete" assessment. Safety was managed by a protocol-specified CRS algorithm with no cases of refractory CRS. Using the Penn CRS grading scale, 82% of patients experienced CRS, with 7 grade 3 (21%) and 8 grade 4 (24%) events. 44% patients with CRS required anti-cytokine therapy; all received tocilizumab with or without other anti-cytokine therapy, with complete resolution of CRS. Besides CRS, the most common grade 3 and 4 non-hematologic AEs were febrile neutropenia (29%), increased bilirubin (21%), increased AST (21%), and hypotension (21%). 21% of patients experienced grade 3 or 4 neuropsychiatric events including confusion, delirium, encephalopathy, agitation and seizure; no cerebral edema was reported. CTL019 in vivo cellular kinetics by qPCR demonstrated transgene persistence in blood in responding patients at and beyond 6 months. Overall exposure (AUC 0-28d) and maximal expansion (Cmax) of CTL019 DNA measured by qPCR was higher in responding compared with non-responding patients. In summary, this pivotal global study in pediatric and young adult patients with r/r B-ALL receiving CTL019, confirms a high level of efficacy and a similar safety profile to that shown in the prior single center experience. Safety was effectively and reproducibly managed by appropriately trained investigators. The study has completed accrual. At the meeting, updated data from a planned formal interim analysis including safety, efficacy (primary and selected secondary endpoints), cellular kinetics, and impact of anti-cytokine therapy will be presented for more than 50 patients infused at 25 global sites. Disclosures Grupp: Jazz Pharmaceuticals: Consultancy; Novartis: Consultancy, Research Funding; Pfizer: Consultancy. Laetsch:Novartis: Consultancy; Loxo Oncology: Consultancy. Bittencourt:Seattle Genetics: Consultancy; Jazz Pharmaceuticals: Consultancy, Other: Educational Grant. Maude:Novartis: Consultancy. Myers:Novartis Pharmaceuticals: Consultancy. Rives:Novartis: Consultancy; Jazz Pharma: Consultancy. Nemecek:Medac, GmbH: Research Funding; Novartis: Consultancy; National Marrow Donor Program: Membership on an entity's Board of Directors or advisory committees. Schlis:Novartis: Honoraria. Martin:Jazz Pharmaceuticals: Other: One time discussion panel; Novartis: Other: Support of clinical trials. Bader:Medac: Consultancy, Research Funding; Riemser: Research Funding; Neovii Biotech: Research Funding; Servier: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Peters:Novartis: Consultancy; Jazz: Speakers Bureau; Amgen: Consultancy; Pfizer: Consultancy; Medac: Consultancy. Biondi:Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Advisory Board; Cellgene: Other: Advisory Board; BMS: Membership on an entity's Board of Directors or advisory committees. Baruchel:Servier: Consultancy; Novartis: Consultancy; Celgene: Consultancy; Jazz: Consultancy; Baxalta: Research Funding. June:University of Pennsylvania: Patents & Royalties; Johnson & Johnson: Research Funding; Celldex: Consultancy, Equity Ownership; Pfizer: Honoraria; Immune Design: Consultancy, Equity Ownership; Novartis: Honoraria, Patents & Royalties: Immunology, Research Funding; Tmunity: Equity Ownership, Other: Founder, stockholder . Sen:Novartis: Employment. Zhang:Novartis: Employment. Thudium:Novartis: Employment. Wood:Novartis Pharmaceuticals: Employment, Other: Stock. Taran:Novartis: Employment. Pulsipher:Chimerix: Consultancy; Jazz Pharmaceutical: Consultancy; Novartis: Consultancy, Other: Study Steering Committee; Medac: Other: Housing support for conference.

The musical Kismet opened on Broadway in 1953. This commercially successful play, translated into a film version released two years later, included some of Jack Cole’s most widely viewed and popular choreography, which resulted in the exposure of Bharata Natyam to a mass audience through its incorporation into jazz dance. Cole’s ‘Hindu swing’ continues to confound years later, even as Bharata Natyam has ever-increasing prominence in global theatre. This article considers how the form, in migration from Madras to Manhattan, was (and is) materialized and reinscribed, discussing how exoticism and Orientalism are implicated in the mechanisms of this transmogrification. Exploring Cole’s involvement with ‘Hindu’ dance calls into question a range of issues related to the parallel histories of musical theatre dance in the mid-twentieth century, and classical Indian dance in the period of transition from colonial possession to postcolonial independence. We investigate the ways in which Indian culture in diaspora has been translated in our practice, and the ways in which the reception of dance reflects an ‘invisibilization’ of ‘foreign’ cultural practice in American popular culture. Collaborating on presenting our juxtaposed experience brings embodied reflection into dialogue with dance scholarship, while also exploring the intersection of these distinct and seemingly discrete dance practices.

Abstract Introduction. Genomic loss of an HLA haplotype encoding incompatible alleles ("HLA loss") has been described in previous single-center studies as a mechanism by which leukemic cells evade the graft-versus-leukemia effect mediated by alloreactive donor T cells and outgrow into a clinically evident relapse. HLA loss accounts for up to 30% of relapses after HLA-haploidentical transplants (Crucitti, Leukemia 2015), but the actual frequency and clinical relevance of this phenomenon in unrelated donor HSCTs, including cord blood transplants, are largely unknown. Here we present the first global collaborative study to investigate the incidence of HLA loss across different transplant settings. Methods. Twenty transplant centers from Europe (n=16), North America (n=3) and Asia (n=1) joined to form the HLALOSS consortium. To date, we collected a total of 619 cases of hematologic relapse from adult patients with acute myeloid leukemia (78.5%), acute lymphoblastic leukemia (13.9%), myelodysplastic syndromes (4%) or myeloproliferative neoplasms (1.1%) after allogeneic HSCT from HLA-haploidentical relatives (31.7%), HLA-mismatched unrelated donors (MMUD, 21.3%), 10/10-matched unrelated donors (MUD, 37.2%), or unrelated cord blood units (UCB, 9.8%). Where available, the donor and patient germlines and the patient pre-transplant disease were collected in parallel. Until today, 476 cases were analyzed using conventional HLA typing of sorted leukemic blasts, the recently developed HLA-KMR assay (Ahci and Toffalori, Blood, 2017) or a novel Next-Generation Sequencing (NGS) method. The latter was developed adapting the HLA typing strategy in use at the DKMS (Lange, BMC Genomics 2013) to the study of chimeric samples, and allowing to cover all possible HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 alleles and to analyze at least 48 different cases in a single run. Results. Out of the 476 relapses analyzed to date, 396 (83.2%) were informative for the study of HLA loss. Of these, 155 occurred after haploidentical HSCT, 101 after MMUD HSCT, 93 after 10/10-matched, HLA-DPB1 mismatched MUD, and 47 after UCB HSCTs. Three-hundred-two (76.2%) of cases were analyzed using the NGS platform. This method resulted particularly robust, reliable and sensitive in analyzing large sample series: the mean coverage across the 6 sequenced loci was over 8500x, up to 0.5% of the HLA allele of interest could be detected in artificial chimerism curves, and relapse samples tested in parallel via the sequencing platform and HLA-KMR (n=10) showed remarkable concordance between the two methods (R2=0.86, p<0.0001). In total, we detected 51 HLA loss post-transplantation relapses out of the 396 cases analyzed (12.8%). Of these, 35 occurred after haploidentical HSCT (22.6% of relapses in this setting), 12 after MMUD HSCT (11.9%), 4 after 10/10 MUD HSCT (4.3%) and, notably, none after UCB HSCT. Conclusions. The present data, obtained from the largest collaborative study on the immunobiology of relapse to date, confirm the clinical relevance of HLA loss as a major mechanism of immune evasion and post-transplantation relapse after allogeneic HSCT, with an incidence which is proportional to the number of donor-recipient HLA mismatches. The only exception is represented by UCB HSCT which, despite being often performed across multiple major HLA incompatibilities, does not appear to be associated with this relapse modality. This finding might reflect the fact that in UCB HSCT, multiple HLA mismatches are often not encoded in cis on the same chromosome, thereby reducing the selective advantage for leukemic cells that undergo an HLA haplotype loss. This phenomenon might in turn contribute to the lower incidence of relapse reported for UCB HSCT compared to other stem cell sources. Disclosures Vago: Moderna TX: Research Funding; GENDX: Research Funding. Stoelzel:Neovii: Speakers Bureau. Gojo:Novartis: Membership on an entity's Board of Directors or advisory committees; Merck inc: Research Funding; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees. Busca:Novartis: Speakers Bureau; Jazz Pharmaceuticals: Honoraria; Pfizer Pharmaceuticals: Honoraria, Speakers Bureau; Merk: Honoraria, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Luznik:WIndMIL Therapeutics: Equity Ownership, Patents & Royalties. Kobbe:Amgen: Honoraria, Research Funding; Celgene: Honoraria, Other: Travel Support, Research Funding; Roche: Honoraria, Research Funding. Kroeger:Novartis: Honoraria, Research Funding; Sanofi: Honoraria; Riemser: Honoraria, Research Funding; Neovii: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; JAZZ: Honoraria. Finke:Neovii: Consultancy, Honoraria, Other: travel grants, Research Funding; Medac: Consultancy, Honoraria, Other: travel grants, Research Funding; Riemser: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Other: travel grants, Research Funding. Mohty:Takeda: Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria; Servier: Consultancy; MaaT Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; Molmed: Consultancy; Jazz Pharmaceuticals: Honoraria, Research Funding, Speakers Bureau; Bristol Myers: Consultancy, Research Funding; Janssen: Honoraria, Research Funding, Speakers Bureau. Beelen:Medac: Consultancy, Other: Travel Support. Fleischhauer:GENDX: Research Funding.

O presente artigo traz uma olhada global sobre os repertórios musicais empregados em cerimônias de xamanismo universal em Brasil. O xamanismo universal configura-se como um movimento de resgate de saberes indígenas tradicionais, sobretudo em relação ao uso de plantas de poder como veículos para a cura física e espiritual. As músicas produzidas dentro deste contexto apresentam-se como um laboratório vivo em que se encontram tradições musicais latino-americanas em constante diálogo com a modernidade e as ferramentas tecnológicas: a musicalidade indígena amazônica, diversas musicalidades populares tradicionais, ritmos folclóricos, jazz, rock, música indiana, entre outros. A partir da escuta de fonogramas, da observação participante de cerimônias e da experiência como intérprete traça-se um mapa das musicalidades que participam deste universo, destacando suas características estilísticas derivadas de seus respectivos meios culturais.

“If you don't learn new songs, you're lost,” Ella Fitzgerald told The New York Times in 1967. This essay is a close reading of one performance of “I Can't Stop Loving You” she gave at a concert in Berlin on February 11, 1968. The song, which had already become a global hit through a version by Ray Charles in 1962, turned into a vehicle through which Fitzgerald signified on “Soulsville,” or soul, a black popular style then sweeping the American music scene. References to Aretha Franklin's “Respect” and Vernon Duke's “I Can't Get Started With You” are examples of the interpolations included here. The essay challenges the idea that the late 1960s were a fallow period in Fitzgerald's career by highlighting the jazz techniques she used to transform one song into a self-revelatory theatrical tour de force.

AbstractPaolo Conte is the most internationally successful of the Italian singer-songwriters who emerged in the 1960s and 1970s. He is also among the most idiosyncratic, eclectic and unusual exponents of what Franco Fabbri has defined as the canzone d’autore (author’s song). Nonetheless he remains a rather arcane, cult figure in the Anglophone world – an example of what Simon Frith has called ‘the unpopular popular’. A combination of apparent opposites – the provincial and the cosmopolitan – his music appropriates a global sweep of influences without being definable as ‘world music’. Characteristics of both his rough, untrained singing style and wry, ironic and opaque compositions have strong affinities with US singer-songwriters like Tom Waits and Randy Newman, and he draws heavily on early American jazz influences, although he remains quintessentially Italian. This makes him difficult to categorise in the world music market.

Abstract Professor Wariboko has rightly responded to Fire from Heaven in the context of the entire span of my writing from The Secular City to The Future of Faith and has pointed out some persistent themes. The thesis of The Secular City was that God remains present and active in a secularizing world, albeit not always under “religious” auspices. A new generation of thinkers, including Charles Taylor, has now picked up this theme. Fire from Heaven described the “surfacing” of this primal piety in the global Pentecostal wave, and The Future of Faith suggests what the next stage may be. The Pentecostal movement and the resurgence of Islam have made it clear that the “secular” is now only one possible worldview among others. Also, there are a number of different forms of secularism. The emerging global cosmopolis will be multicultural, a world city “where strangers meet.” Using the metaphor of jazz, faith now follows no “score” but improvises within a chord structure, with players responding to each other. The question of whether the Pentecostal movement can “play” in such a setting is still an open one.

Background. In recent years, there has been an increasing interest in research of global and pivotal changes of world’s sound image in musical art, this shift being incarnated in a tendency towards conception of new sound images of music instruments, which would be simultaneously relevant to new sound realm and being capable of “encapsulating” culture’s memory and experience. The domra, which is one of the carriers of this cultural memory, has its sound image transfigured in dimensions of academic, folklore, jazz and stage types of performance traditions in the works by V. Solomin. The objectives of this study to reveal ways of creative self-identification of V. Solomin as well as of conception of domra’s new sound image in his works. The complex of the analytical methods (analysis, synthesis, comparative studies), as well as the historical-typological approach was used in this research. Results of the research. Specific of world’s modern sound image is marked by conceptualization of a sound, destruction of established hierarchy of means of musical expression and new understanding of statuses of musical instruments. These features transpire in creation of new sonic images of musical instruments, including the domra, whose evolution during XX century was connected with the academic tradition of music. On the verge of XX–XXI centuries ample transformations of instrument’s sound image, related to diffusion, intertextuality and plurality of modern culture, are stamped in the creativity of those connected to the Ukrainian domra art. In V. Solomin’s creativity the sound image of the domra is characterized by universality, as in different forms of performance (such as solo, ensemble, orchestral) this instrument appeals to stylistic layers of folklore, classical academic heritage of various cultural epochs as well as to new kinds of art, the one of stage and jazz. Classical musical pieces being interpreted for the domra by V. Solomin allow to broaden vistas of perception of this instrument since they represent “known” content in new and somewhat unexpected timbre variant, thus creating re-intonation and re-semantization of content. Personal re-intonation and re-semantization in the interpretation of J. S. Bach’s works, carried out by V. Solomin, relies on modification of articulation and new understanding of source’s timbre characteristics; it is a complex intertwining of pre-Baroque, Baroque and modern performance art, as well as of lute, violin and domra traditions, and of modern and academic layers of musical performing. Innovation of domra’s sound image implies accretion of its repertoire with “modern classics” as well. V. Solomin’s interpretation of A. Schnittke’s “Suite in Old Style” might be seen as “condensed” reincarnation of spiritual values, manipulation with signs of the Past (for instance, Baroque era), crucial for postmodern culture. Another aspect of innovation of the domra’s sound image lies in the fact that V. Solomin adds to its repertoire pieces, not quite traditional for its national and stylistic appeal. In this regard, interpretation of I. Alb&#233;niz’s “Asturias” becomes multi-layered combination of signs, typical for different cultures. This transcription manifests stylistic mobility of domra’s sound image as well as its capability to adapt to technical devices, stemming from other instruments. The fact that V. Solomin created two bands, “Solominband” (2004) and “DomRa” (2009), proves ability of the domra’s sound image to undergo drastic stylistic modifications. The activity of “Solominband” (including a project in partnership with the singer Katia Chilly) and “DomRa” demonstrated author’s intentional orientation towards synthesis of authentic tradition and jazz, desire to reveal timbre colors of the domra, special attention to the sound as a carrier of intonation sense, understanding of the domra’s leading role in the context of ensemble performance while simultaneously proclaiming “performer’s equality”, its reflexivity and co-dependence from other participants of the ensemble. Expansion of timbre, articulatory, dynamical and technical “aura” of the domra, achieved by usage of its electric variant, allowed the author to create large-scaled multi-layered synthesis of cultures: authentic (Ukrainian, Celtic, Latin-American), academic, jazz and rock. Electric variant of the domra enriched expressive and technical possibilities of the domra art with now ways of playing, while also added variety to timbre-sonic layers of modern jazz and rock, thus becoming a basis for new stylistic mixes. As an example of such mix, we can regard V. Solomin’s versions of modern pop-music. Program “The Rain”, based on interpretations of songs by Sting (G. M. T. Sumner) is marked by synthesis of folklore, jazz and pop-music (which is relevant to pluralistic foundations of modern multi-culture); by representation of sound image of the domra as of the instrument, capable of recreation of vocal cantilena; by rich palette of technical and expressive devices; by functional versatility of the domra, acquiring both solo and accompaniment roles, as well as status of bearer of a melodic line and stimulus of intonation and rhythmic movement, instigator of jazz-like “improvisatory competition” etc. Conclusions. The present results are significant in understanding that creativity of V. Solomin foreshadows new vectors of the domra art’s evolution and re-semantization of its sound image. The domra’s modulation into spheres of academic musical art, pop and rock culture, authentic performance and jazz results in new, culturally polyphonic sound image of this instrument and its new status of the poly-functional multi-stylistic mediator between cultural dimensions, of concentrated, timbre-sonic expressive, and conceptually flexible carrier of cultural memory. Perspectives of further research lie in examination of features, characteristic for interpretations of the domra’s innovative sound image by Ukrainian musicians who work in the sphere of the domra music, including jazz, pop and rock music.

Near-infrared (NIR) spectroscopy has been widely reported for its useful applications in assessing internal fruit qualities. Motivated by apple consumption in the global market, this study aims to evaluate the possibility of applying NIR imaging to detect slight bruises in apple fruits. A simple optical setup was designed, and low-cost system components were used to promote the future development of practical and cost-efficient devices. To evaluate the effectiveness of the proposed approach, slight bruises were created by a mild impact with a comparably low impact energy of only 0.081 Joules. Experimental results showed that 100% of bruises in Jazz and Gala apples were accurately detected immediately after bruising and within 3 hours of storage. Thus, it is promising to develop customer devices to detect slight bruises for not only apple fruits but also other fruits with soft and thin skin at their early damage stages.

Abstract Music is intimately implicated in racialising discourses. This is particularly pronounced in the case of so-called black music, i.e. the types of music that are commonly associated with African-American identity, most notably jazz and various forms of popular music. Genres of popular music are furthermore constructed continuously on the basis of a notion of their “black roots.” The idea of the “black roots” of jazz and popular music is an essential ingredient of Paul Gilroy’s (1993) analysis of a specific authenticity of blackness. To stress the history and consequences of the pre-twentieth century slave trade and institutionalised racism, Gilroy has coined the concept “Black Atlantic” that builds on the idea of a distinct double consciousness inherent in blackness as simultaneously a fundamental constituent and the ultimate other of the West. In the article, I aim at rethinking the notion of the Black Atlantic in relation to North-Eastern Europe. By way of marine analogy I ask, and building on the notions of the Black Pacific and the Black Mediterranean, how to formulate an analytical design “the Black Baltic Sea.” In addition to addressing the impact of global racialising tendencies in music, this entails considering the cultural dynamics at issue in relation to the dynamics of postsocialism in the Baltic Sea Region (BSR) and Northern European indigeneity. On the basis of such a consideration, I argue that the styles of “black music” have been appropriated and adopted throughout the BSR, albeit in clearly different national manifestations which for their part imply variegated intersections between postcolonial and postsocialist processes. These intersections become manifest in the discourses over “new Europeanness” in music and the construction of national musical traditions, particularly when juxtaposed with the prevailing Islamophobia as regards treatments of Muslim music in mainstream media.

Abstract Background: The development of new genetic profiling techniques such as Next Generation Sequencing (NGS) have helped to unravel the genomic landscape of a large number of hematological diseases. In acute myeloblastic leukemia (AML), many mutations have been found at diagnosis or during the course of the disease, either alone or in combination. Nevertheless, the clinical significance of most of them has not been well established. That is particularly true regarding infrequent gene mutations and their co-mutations as they are underrepresented in most case series that have been analyzed so far. The big data platform of HARMONY alliance provides the excellent basis for addressing this problem as it assimilates clinical and genomic information about AML patients from over 100 organisations in 18 European countries comprising more than 5000 patients. Anonymised and harmonized using OMOP standards, data collected in HARMONY are optimal for studying the impact of gene-gene-interactions overcoming differences related to data providers. Aims: To identify clinically significant genetic patterns of 2 or more concurrent mutations using the Harmony alliance AML database Methods: From the HARMONY alliance database, we selected ~3600 AML patients with NGS molecular panel analysis. We first performed survival analysis between each gene combination and then we rendered those with statistically significant differences in one easy-to-read graph using the Gephi platform (Fig. A). We then highlighted promising or unexpected associations and analyzed them one by one in greater detail. Finally, these results were validated on an independent cohort. Results: We found that the co-mutation of RAD21 (RAD21mut) in DNMT3A mutated (DNMT3Amut) AML impacted outcome compared to DNMT3Amut alone patients (Fig. B, 3-year survival, 81% vs 52%, p=0.016). However, this effect was exclusively seen in allogeneic transplant recipients. In order to identify possible bias that could be generated if RAD21mut were associated with other well-known favorable prognosis mutations, we compared the frequency of each mutation in our DNMT3Amut / RAD21mut subgroup with the global AML cohort. NPM1 co-mutation was more frequent in the DNMT3Amut / RAD21mut group (Fig. C 3, 84% of patients with NPM1 mutation (NPM1mut) vs 26% in the global cohort), potentially explaining the higher survival. Next, we tried to isolate the positive effect of NPM1 on outcome by comparing DNMT3Amut / NPM1mut patients with and without the RAD21 co-mutation. This analysis showed a favorable outcome only in RAD21mut patients compared to RAD21 wildtype (Fig. D, 3-year survival, 83% in RAD21mut / DNMT3Amut / NPM1mut vs 50% in DNMT3Amut / NPM1mut with RAD21 wildtype, p=0.016), one more time only in allogeneic transplant recipients. Finally in order to validate our results we reproduced this study from the beginning using an independent cohort of 3125 AML patients. The Gephi graph confirmed an association of DNMT3Amut / RAD21mut patients with better survival over DNMT3A alone (3 year-survival, 75% vs 37%, p&lt;0.001). NPM1 co-mutation was again more frequent in the good prognosis group (76% vs 27%) but comparing RAD21mut / DNMT3Amut / NPM1mut patients with DNMT3Amut / NPM1mut alone still revealed good prognosis to be related with RAD21mut (3 year-survival, 87.5% in patients with RAD21mut vs 38% with RAD21 wildtype, p&lt;0.001). Conclusions: Using the HARMONY alliance database we tested for potential gene co-mutations in AML patients, often very infrequently represented in other studies. Our data suggest that RAD21mut has a positive effect on outcome in patients receiving an allogeneic transplant with concurrent mutation of DNMT3A and NPM1. Even though NPM1mut is much more frequent in the DNMT3Amut / RAD21mut group, its association with favourable outcome seems to depend on the presence of an additional RAD21mut Keywords: AML , gene combinations, RAD21, DNMT3A, NPM1, HARMONY, big data. Figure: Graphical results. A. View obtained from the Gephi platform with the gene combinations and their effect on survival. B. Survival curves respectively of the DNMT3A+RAD21 cohort and the DNMT3A-only one. 1. Representation of the proportions of each mutation in the overall cohort (red) compared to the DNMT3A+RAD21 cohort (blue). D. Survival curves respectively of the NPM1+DNMT3A+RAD21 cohort and the NPM1+DNMT3A one. Figure 1 Figure 1. Disclosures Sobas: Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Heckman: Novartis: Research Funding; Orion Pharma: Research Funding; Celgene/BMS: Research Funding; Oncopeptides: Consultancy, Research Funding; Kronos Bio, Inc.: Research Funding. Ayala: Incyte Corporation: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Honoraria; Celgene: Honoraria. Dombret: Amgen: Honoraria, Research Funding; Incyte: Honoraria, Research Funding; Jazz Pharmaceuticals: Honoraria, Research Funding; Novartis: Research Funding; Pfizer: Honoraria, Research Funding; Servier: Research Funding; Abbvie: Honoraria; Daiichi Sankyo: Honoraria; BMS-Celgene: Honoraria. Sierra: Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz Pharmaceuticals: Research Funding; Novartis: Honoraria, Research Funding, Speakers Bureau; BMS Celgene: Honoraria, Research Funding; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Honoraria; Roche: Other: Educational grant; Janssen: Other: Educational grant; Amgen: Other: Educational grant; Alexion: Other: Educational grant. Mayer: Principia: Research Funding. Voso: Celgene: Consultancy, Research Funding, Speakers Bureau; Novartis: Speakers Bureau. Sanz: Helsinn Healthcare: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Boehringer Ingelheim: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, and expenses; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, and expenses, Speakers Bureau; Gilead Sciences: Other: Travel, accommodations, and expenses; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, and expenses, Research Funding. Calado: Novartis: Current Employment. Döhner: Janssen: Honoraria, Other: Advisory Board; Jazz Roche: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Astellas: Research Funding; Agios and Astex: Research Funding; Daiichi Sankyo: Honoraria, Other: Advisory Board; Celgene/BMS: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Gaidzik: Janssen: Speakers Bureau; Pfizer: Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Heuser: AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Research Funding; BergenBio: Research Funding; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees, Research Funding; Tolremo: Membership on an entity's Board of Directors or advisory committees; Astellas: Research Funding; Bayer Pharma AG: Research Funding. Haferlach: MLL Munich Leukemia Laboratory: Other: Part ownership. Turki: Jazz Pharma: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau; CSL Behring: Consultancy. Schulze-Rath: Bayer: Current Employment. Hernández Rivas: Celgene/BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees. Bullinger: Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Hexal: Consultancy; Gilead: Consultancy; Abbvie: Consultancy, Honoraria; Menarini: Consultancy; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Amgen: Honoraria; Astellas: Honoraria; Sanofi: Honoraria; Seattle Genetics: Honoraria; Bayer: Research Funding. Döhner: Jazz: Honoraria, Research Funding; Janssen: Honoraria; GEMoaB: Honoraria; Astellas: Honoraria, Research Funding; Astex: Honoraria; Agios: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Roche: Honoraria; Pfizer: Research Funding; Novartis: Honoraria, Research Funding; Oxford Biomedicals: Honoraria; Helsinn: Honoraria; BMS: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; AstraZeneca: Honoraria; Berlin-Chemie: Honoraria; Amgen: Honoraria, Research Funding. Ossenkoppele: Servier: Consultancy, Honoraria; Agios: Consultancy, Honoraria; Abbvie, AGIOS, BMS/Celgene Astellas,AMGEN, Gilead,Servier,JAZZ,Servier Novartis: Consultancy, Honoraria; Jazz: Consultancy, Honoraria; BMS/Celgene: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Gilead: Consultancy, Honoraria.

Abstract Background: Guadecitabine (G) is a next generation subcutaneous (SC) hypomethylating agent (HMA) resistant to degradation by cytidine deaminase which results in prolonged in vivo exposure to the active metabolite decitabine. We conducted a large global randomized phase 3 study (ASTRAL-2) of G vs TC in AML patients who were either refractory to or relapsed (r/r) after prior anthracycline-based intensive chemotherapy with or without hematopoietic cell transplant (HCT). Methods: r/r AML patients were randomized to G (60 mg/m 2 SC/d for 10 days in first 1-2 cycles followed by 5-day cycles Q 28 days) vs Treatment Choice (TC). TC were preselected prior to randomization to either low intensity (LI) treatment; high intensity (HI) chemotherapy; or Best Supportive Care (BSC). LI choices were other HMAs of azacitidine or decitabine, or low-dose Ara-C (LDAC) at their standard doses. HI choices were high-dose Ara-C (HiDAC), MEC, or FLAG± Ida combination chemotherapy at standard doses. Primary endpoint was overall survival (OS) based on ITT analysis with secondary endpoints including 12 and 24-month survival rates, complete response (CR), event-free survival (EFS), and safety. P values for secondary endpoints and subgroups are nominal as there was no adjustment of p values for multiple analyses. Results: 302 patients were randomized to G (148) or TC (154). Preselected TCs were mainly LI (77%) predominantly HMAs (86% of the patients randomized to LI), or HI (21%), with only 6 patients (2%) in the BSC subset. Baseline variables were well balanced across the 2 treatment arms. For G vs TC respectively, age ≥65 y in 51.4% vs 40.3% with median age 65y vs 63y, ECOG PS 2 in 15.5% vs 20.8%, poor risk cytogenetics in 44.6% vs 42.2%, refractory AML in 44.6% vs 33.1%, prior HCT in 18.2% vs 26%, a majority of patients were in second or subsequent relapse after ≥ 2 prior therapies (54.7% vs 56.5%). Median number of treatment cycles was short (3 cycles for G vs 2 cycles for TC). Median follow up was 21.6 months. Most common causes of treatment discontinuation were disease progression (35.2% for G vs 38.1% for TC), or death (15.2% for G vs 18.4% for TC). Median OS on G was 6.4 months vs 5.4 months for TC and not statistically significant (OS HR 0.88, 95% CI 0.67, 1.14, log rank p value 0.3). There was no significant difference in OS between G and each of the LI and HI preselected subsets. However, several other planned prospective subgroups favored G with OS HR 95% CI upper limit ≤ 1.0 including patients &lt;65y (HR 95% CI 0.47, 0.97, p 0.032) ; ECOG PS 0-1 (HR 95% CI 0.57, 1.0, p 0.049); refractory AML (HR 95% CI 0.38, 0.89, p 0.013); lower peripheral blood (PB) disease burden of ≤ 30% PB blasts (HR 95% CI 0.46, 0.92, p 0.015); and those who received at least 4 cycles in either treatment arm (HR 95% CI 0.36, 0.95 , p 0.031). The 12- and 24-month survival rates for G vs TC respectively were 32% vs 26%; and 19% vs 10%. Median EFS was short with 3 months for G vs 2.4 months for TC; log rank p 0.005. CR rate was 12.8% for G vs 7.1% for TC (p 0.051). CR + CR with partial hematologic recovery (CRh) rate was double for G with 16.9% compared to 7.8% for TC (p 0.007). Composite CR (CRc) or CR+ CR with incomplete hematologic recovery (CRi) rate was 27% for G vs 14.3% for TC (p 0.003). Adverse events (AEs) of grade ≥3, regardless of relationship to treatment, were 89% on G vs 84% on TC. Most common Grade ≥3 AEs for G vs TC respectively were febrile neutropenia (38.6% vs 38.1%); neutropenia (32.4% vs 17%); thrombocytopenia (28.3% vs 29.9%); anemia (21.4% vs 24.5%); pneumonia (18.6% vs 20.4%); and sepsis (11.7 vs 10.9%). None of the differences were significant except for neutropenia (p 0.003). Summary/Conclusions: In this randomized study in r/r AML after intensive chemotherapy, G did not significantly improve OS compared to standard of care TC composed mainly of LI treatment with other HMAs. The data suggest that G may be better than TC in in some of the secondary endpoints (24-month survival rate, EFS, CR, CR+CRh, and CRc). Prospective subgroup analyses of OS suggest that younger (&lt;65 y), more fit patients (PS 0-1); with lower PB disease burden (PB blasts ≤ 30%), and those who could receive at least 4 cycles may benefit from G. The results of secondary endpoints and subgroup analyses should be interpreted with caution. Grade ≥3 AEs were the expected hematological and infection AEs with no significant differences between G and TC except for significantly higher incidence of neutropenia with G. Disclosures Roboz: Actinium: Consultancy; Mesoblast: Consultancy; Janssen: Research Funding; AbbVie: Consultancy; Astex: Consultancy; AstraZeneca: Consultancy; Novartis: Consultancy; Agios: Consultancy; Glaxo SmithKline: Consultancy; Blueprint Medicines: Consultancy; Janssen: Consultancy; Jasper Therapeutics: Consultancy; Amgen: Consultancy; Astellas: Consultancy; Bristol Myers Squibb: Consultancy; Celgene: Consultancy; MEI Pharma - IDMC Chair: Consultancy; Helsinn: Consultancy; Bayer: Consultancy; Daiichi Sankyo: Consultancy; Jazz: Consultancy; Otsuka: Consultancy; Pfizer: Consultancy; Roche/Genentech: Consultancy. Sanz: Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead Sciences: Other: Travel, accommodations, and expenses; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, and expenses; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, and expenses, Speakers Bureau; Helsinn Healthcare: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, and expenses, Research Funding. Griffiths: Novartis: Honoraria; Abbvie: Consultancy, Honoraria; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Taiho Oncology: Consultancy, Honoraria; Apellis Pharmaceuticals: Research Funding; Astex Pharmaceuticals: Honoraria, Research Funding; Genentech: Research Funding; Boston Biomedical: Consultancy; Alexion Pharmaceuticals: Consultancy, Research Funding; Takeda Oncology: Consultancy, Honoraria. Yee: Forma Therapeutics: Research Funding; Astex: Membership on an entity's Board of Directors or advisory committees, Research Funding; F. Hoffmann La Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; TaiHo: Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Paladin: Membership on an entity's Board of Directors or advisory committees; Otsuka: Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria; Bristol-Myers Squibb/Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Onconova: Research Funding; Tolero: Research Funding; Jazz: Research Funding; MedImmune: Research Funding; Geron: Research Funding; Janssen: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Shattuck Labs: Membership on an entity's Board of Directors or advisory committees. Kantarjian: Daiichi-Sankyo: Research Funding; BMS: Research Funding; Ipsen Pharmaceuticals: Honoraria; Astellas Health: Honoraria; Aptitude Health: Honoraria; KAHR Medical Ltd: Honoraria; Astra Zeneca: Honoraria; Pfizer: Honoraria, Research Funding; Ascentage: Research Funding; Amgen: Honoraria, Research Funding; Immunogen: Research Funding; Novartis: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; Precision Biosciences: Honoraria; Jazz: Research Funding; NOVA Research: Honoraria; Taiho Pharmaceutical Canada: Honoraria. Recher: Incyte: Honoraria; Janssen: Honoraria; Jazz: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Macrogenics: Honoraria, Membership on an entity's Board of Directors or advisory committees; MaatPharma: Research Funding; Astellas: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS/Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Agios: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Byrne: Karyopharm: Research Funding. Patkowska: Astellas Pharma, Inc.: Consultancy, Other: Travel fees; KCR US, Inc.: Consultancy; Bristol-Myers Squibb: Other: Travel fees; Jazz Pharmaceuticals: Other: Travel fees; Angelini Pharma: Honoraria, Other: Travel fees; Novartis: Honoraria, Other: Travel fees; Servier: Honoraria, Other: Travel fees; Pfizer: Other: Travel fees; AMGEN: Honoraria. Kim: AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AIMS Biosciense: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; AML-Hub: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BL & H: Research Funding; BMS & Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Boryung Pharm Co.: Consultancy; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Handok: Consultancy, Honoraria; LG Chem: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria; Pintherapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi Genzyme: Honoraria, Speakers Bureau; SL VaxiGen: Consultancy, Honoraria; VigenCell: Consultancy, Honoraria. Stock: Pfizer: Consultancy, Honoraria, Research Funding; amgen: Honoraria; agios: Honoraria; jazz: Honoraria; kura: Honoraria; kite: Honoraria; morphosys: Honoraria; servier: Honoraria; syndax: Consultancy, Honoraria; Pluristeem: Consultancy, Honoraria. Illes: Janssen, Celgene, Novartis, Pfizer, Takeda, Roche: Consultancy; Takeda, Seattle Genetics: Research Funding; Novartis, Janssen, Pfizer, Roche: Other: Travel, Accommodations, Expenses. Fenaux: Abbvie: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; JAZZ: Honoraria, Research Funding; Celgene/BMS: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Syros Pharmaceuticals: Honoraria. Miyazaki: Pfizer: Honoraria; Bristol-Myers Squibb: Honoraria; Abbvie: Honoraria; Novartis: Honoraria; Nippon-Shinyaku: Honoraria; Chugai: Honoraria; Janssen: Honoraria; Sumitomo-Dainippon: Honoraria, Research Funding; Astellas: Honoraria; Eisai: Honoraria; Daiichi-Sankyo: Honoraria; Takeda: Honoraria; Kyowa-Kirin: Honoraria; Sanofi: Honoraria. Yamauchi: Daiichi Sankyo: Research Funding; Astellas: Research Funding; Abbie: Research Funding; Chugai: Honoraria; Pfizer: Honoraria, Research Funding; Ono Pharmaceutical: Honoraria; Otsuka: Research Funding; Solasia Pharma: Research Funding. Hao: Astex Pharmaceuticals, Inc.: Current Employment. Keer: Astex Pharmaceuticals, Inc.: Current Employment. Azab: Astex Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees. Dohner: Celgene: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; Berlin-Chemie: Honoraria; Abbvie: Honoraria, Research Funding; AstraZeneca: Honoraria; Agios: Honoraria, Research Funding; Astex Pharmaceuticals: Honoraria; Amgen: Honoraria, Research Funding; Astellas: Honoraria, Research Funding; GEMoaB: Honoraria; Gilead: Honoraria; Helsinn: Honoraria; Janssen: Honoraria; Jazz Pharmaceuticals: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Oxford Biomedica: Honoraria; Pfizer: Research Funding; Roche: Honoraria.

Abstract Background: Overexpression of CD123 is characteristic of a number of hematological malignancies, including acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN). IMGN632 is a CD123-targeting antibody-drug conjugate (ADC) with a novel anti-CD123 antibody coupled to a unique DNA-alkylating payload of the recently developed IGN (indolinobenzodiazepine pseudodimer) class of payloads. In preclinical models of AML, IMGN632 exhibited potent anti-leukemia activity, with a wide therapeutic index. Confirming preclinical expectations, encouraging single-agent activity and favorable tolerability were observed in the Phase I trial (Daver ASH 2019, Blood 2019, vol 134, suppl 1, 734). Preclinical data from AML xenograft models have demonstrated synergy in IMGN632 combinations with azacitidine and venetoclax (Kuruvilla ASH 2020, Blood 2020, vol 136, suppl 1, 32-33), supporting the exploration of these combinations in AML patients. Methods: This Phase 1b/2 study is designed to determine the safety, tolerability, and preliminary anti-leukemia activity of IMGN632 when administered in combination with azacitidine and venetoclax to patients with relapsed and frontline CD123-positive AML, and the single-agent activity of IMGN632 in patients with minimal residual disease (MRD)-positive AML in frontline or 1 st salvage treatment. Study Design: Adult patients with CD123-positive relapsed or refractory AML, who are deemed appropriate for experimental therapy, are eligible to enroll as part of the dose escalation phase. Key exclusion criteria for all regimens include active central nervous system disease, and history of sinusoidal obstruction syndrome/venous occlusive disease of the liver. Current enrollment is focused on the triplet, IMGN632 plus azacitidine and venetoclax (IMGN632+AZA+VEN). Once an RP2D is selected, Phase 2 dose expansion will further characterize the safety profile and assess antileukemia activity in frontline or relapsed AML patients. In addition, IMGN632 monotherapy is being explored in expansion cohorts of MRD-positive patients to assess conversion rate from MRD+ to MRD- and RFS in both fit and unfit AML subpopulations (NCT04086264). IMGN632 is also being tested as a monotherapy in a pivotal cohort for adults with frontline BPDCN (NCT03386513, https://BPDCNtrial.com). Disclosures Daver: FATE Therapeutics: Research Funding; Sevier: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Hanmi: Research Funding; Genentech: Consultancy, Research Funding; Glycomimetics: Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Trillium: Consultancy, Research Funding; Gilead Sciences, Inc.: Consultancy, Research Funding; ImmunoGen: Consultancy, Research Funding; Novimmune: Research Funding; Abbvie: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Trovagene: Consultancy, Research Funding; Novartis: Consultancy; Jazz Pharmaceuticals: Consultancy, Other: Data Monitoring Committee member; Dava Oncology (Arog): Consultancy; Celgene: Consultancy; Syndax: Consultancy; Shattuck Labs: Consultancy; Agios: Consultancy; Kite Pharmaceuticals: Consultancy; SOBI: Consultancy; STAR Therapeutics: Consultancy; Karyopharm: Research Funding; Newave: Research Funding. Aribi: Seagen: Consultancy. Montesinos: Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Teva: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Stemline/Menarini: Consultancy; Forma Therapeutics: Consultancy; Glycomimetics: Consultancy; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; Tolero Pharmaceutical: Consultancy; Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Agios: Consultancy; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Astellas Pharma, Inc.: Consultancy, Honoraria, Other: Advisory board, Research Funding, Speakers Bureau. Roboz: Novartis: Consultancy; Agios: Consultancy; Helsinn: Consultancy; AstraZeneca: Consultancy; Jasper Therapeutics: Consultancy; Jazz: Consultancy; Celgene: Consultancy; MEI Pharma - IDMC Chair: Consultancy; Janssen: Research Funding; Blueprint Medicines: Consultancy; Bayer: Consultancy; AbbVie: Consultancy; Daiichi Sankyo: Consultancy; Glaxo SmithKline: Consultancy; Janssen: Consultancy; Bristol Myers Squibb: Consultancy; Astex: Consultancy; Amgen: Consultancy; Actinium: Consultancy; Astellas: Consultancy; Mesoblast: Consultancy; Otsuka: Consultancy; Pfizer: Consultancy; Roche/Genentech: Consultancy. Wang: DAVA Oncology: Consultancy, Speakers Bureau; Takeda: Consultancy, Honoraria, Other: Advisory board; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kura Oncology: Consultancy, Honoraria, Other: Advisory board, steering committee, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Honoraria, Other: Advisory Board; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy, Honoraria, Other: Advisory Board; Stemline Therapeutics: Consultancy, Honoraria, Other: Advisory board, Speakers Bureau; Kite Pharmaceuticals: Consultancy, Honoraria, Other: Advisory Board; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Other: Advisory Board; Mana Therapeutics: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Other: Advisory Board, Speakers Bureau; Rafael Pharmaceuticals: Other: Data safety monitoring committee; Gilead: Consultancy, Honoraria, Other: Advisory board; Daiichi Sankyo: Consultancy, Honoraria, Other: Advisory board; PTC Therapeutics: Consultancy, Honoraria, Other: Advisory board; Genentech: Consultancy; MacroGenics: Consultancy. Walter: Agios Pharmaceuticals, Inc.: Consultancy, Research Funding; Amgen, Inc.: Consultancy, Research Funding; Amphivena Therapeutics, Inc.: Current equity holder in publicly-traded company; Aptevo Therapeutics, Inc.: Consultancy, Research Funding; Arog Pharmaceuticals, Inc.: Research Funding; Astellas Pharma US, Inc.: Consultancy; BioLineRx, Ltd.: Consultancy, Research Funding; Boston Biomedical, Inc.: Consultancy; Bristol Myers Squibb, Inc.: Consultancy; Celgene, Inc.: Consultancy, Research Funding; Genentech, Inc.: Consultancy; GlaxoSmithKline, Inc.: Consultancy; ImmunoGen, Inc.: Research Funding; Janssen Global Services, LLC: Consultancy; Janssen Research & Development, Inc.: Research Funding; Jazz Pharmaceuticals, Inc.: Consultancy, Research Funding; Kite Pharma, Inc.: Consultancy; Kronos Bio, Inc.: Consultancy; Kura Oncology, Inc.: Research Funding; Macrogenics, Inc.: Research Funding; New Link Genetics: Consultancy; Pfizer, Inc.: Consultancy, Research Funding; Race Oncology Ltd.: Consultancy; Selvita: Research Funding; Stemline Therapeutics, Inc.: Research Funding. Jeyakumar: Jazz: Research Funding; Pfizer: Research Funding. DeAngelo: GlycoMimetics: Research Funding; Forty-Seven: Consultancy; Abbvie: Research Funding; Autolus: Consultancy; Incyte Corporation: Consultancy; Shire: Consultancy; Blueprint Medicines Corporation: Consultancy; Amgen: Consultancy; Agios: Consultancy; Jazz: Consultancy; Novartis: Consultancy, Research Funding; Pfizer: Consultancy; Takeda: Consultancy. Erba: AbbVie Inc; Agios Pharmaceuticals Inc; ALX Oncology; Amgen Inc; Daiichi Sankyo Inc; FORMA Therapeutics; Forty Seven Inc; Gilead Sciences Inc; GlycoMimetics Inc; ImmunoGen Inc; Jazz Pharmaceuticals Inc; MacroGenics Inc; Novartis; PTC Therapeutics: Research Funding; AbbVie Inc: Other: Independent review committee; AbbVie Inc; Agios Pharmaceuticals Inc; Bristol Myers Squibb; Celgene, a Bristol Myers Squibb company; Incyte Corporation; Jazz Pharmaceuticals Inc; Novartis: Speakers Bureau; AbbVie Inc; Agios Pharmaceuticals Inc; Astellas; Bristol Myers Squibb; Celgene, a Bristol Myers Squibb company; Daiichi Sankyo Inc; Genentech, a member of the Roche Group; GlycoMimetics Inc; Incyte Corporation; Jazz Pharmaceuticals Inc; Kura Oncology; Nov: Other: Advisory Committee. Advani: Abbvie: Research Funding; Macrogenics: Research Funding; Pfizer: Honoraria, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; OBI: Research Funding; Immunogen: Research Funding; Glycomimetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding. Martinelli: Incyte: Consultancy; Pfizer: Consultancy, Speakers Bureau; Daichii Sankyo: Consultancy; Astellas: Consultancy, Speakers Bureau; Jazz Pharmaceuticals: Consultancy; Celgene /BMS: Consultancy, Speakers Bureau; Roche: Consultancy; Abbvie: Consultancy; Stemline Therapeutics: Consultancy. Gastaud: PFIZER: Consultancy; CELGENE/BMS: Consultancy; ABBVIE: Consultancy; GSK: Consultancy. Altman: Biosight: Membership on an entity's Board of Directors or advisory committees, Other: reimbursement for travel, Research Funding; ImmunoGen: Research Funding; Kartos Therapeutics: Research Funding; Kura Oncology: Membership on an entity's Board of Directors or advisory committees, Research Funding; Fujifilm: Research Funding; Glycomimetics: Other: data monitoring committee; Loxo: Research Funding; Celgene: Research Funding; Boehringer Ingelheim: Research Funding; Astellas: Honoraria, Research Funding; Aptos: Research Funding; Aprea: Research Funding; Amgen: Research Funding; Abbvie: Honoraria, Research Funding; ALX Oncology Inc.: Research Funding; Syros: Membership on an entity's Board of Directors or advisory committees. de la Fuente: Incyte: Consultancy, Speakers Bureau; Abbie: Consultancy, Speakers Bureau; Novartis: Research Funding; BMS: Consultancy, Speakers Bureau. Gaidano: Incyte: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; Astrazeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Curti: Jazz Pharma: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees. Boissel: Servier: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; PFIZER: Consultancy, Honoraria; Bristol-Myers Squibb: Honoraria, Research Funding; CELGENE: Honoraria; Amgen: Consultancy, Honoraria, Research Funding; JAZZ Pharma: Honoraria, Research Funding; SANOFI: Honoraria; Incyte: Honoraria. Recher: Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Macrogenics: Honoraria, Membership on an entity's Board of Directors or advisory committees; MaatPharma: Research Funding; Jazz: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria; Incyte: Honoraria; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS/Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Agios: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Schliemann: Philogen S.p.A.: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Other: travel grants; Astellas: Consultancy; AstraZeneca: Consultancy; Boehringer-Ingelheim: Research Funding; BMS: Consultancy, Other: travel grants; Jazz Pharmaceuticals: Consultancy, Research Funding; Novartis: Consultancy; Roche: Consultancy; Pfizer: Consultancy. Wang: Immunogen: Current Employment. Malcolm: Immunogen: Current Employment. Zweidler-McKay: ImmunoGen: Current Employment. Sweet: Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; AROG: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Bristol Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Background: Multiple myeloma (MM), is a clonal plasma cell neoplasm characterized by destructive bony lesions, anemia, and renal impairment. MM is a global disease - worldwide in 2016, there were 138509 incident cases with an age standardized incidence rate (ASIR) of 2.1 per 100 000 persons, with a 126% global increase in incident cases from 1990 to 2016 (Cowan AJ et al JAMA Oncology 2018). Access to effective care, including proteasome inhibitors, immunomodulatory agents, and autologous hematopoietic stem cell transplantation (HSCT) is largely limited to high-income sociodemographic index (SDI) countries. SCT remains the standard of care for eligible patients, and in general is more affordable and accessible worldwide than novel therapies. We sought to evaluate the rates and utilization of ASCT globally from 2006-2015 to better characterize access to SCT for patients with MM. Methods: This was a new analysis of a retrospective survey of WBMT sites, conducted annually between 2006-2015, as described previously (Niederwieser et al BMT 2016). Incidence data estimates were reported from the Global Burden of Disease study (Institute for Health Metrics and Evaluation. 2019 'GBD Results Tool.' Global Health Data Exchange. Seattle WA: University of Washington. Accessed 1 June 2019). South Asia and East Asia regions were combined for this analysis. Outcome measures included total number of autologous and allogeneic stem cell transplants by World Bank (WB) regions, and percentage of newly diagnosed MM patients who underwent ASCT, calculated by the number of transplants per region in calendar year / gross annual incidence of MM per region. Results: From 2006 to 2015, the number of autologous HSCT performed worldwide for MM increased by 107% (Figure 1). Activity increased in each region from 2006 to 2015 from 56% in USA and Canada to 335% in Latin America. Utilization of autologous HSCT was highest amongst the Northern America and European WB regions, with an increase from 13% to 24% in Northern America, and an increase from 15% to 22% in Europe. The activity increased considerably in the Latin American countries (335,46% increase) and the utilization reached &gt;10%. In contrast, the utilization of autologous HSCT was much lower in the Africa/Mediterranean and Asian/Pacific region, with autologous HSCT utilization only changing marginally from 1.8% in 2006 to 4% in 2015 despite increase in activity. The number of first allogeneic HSCT performed globally for MM declined after a peak in 2012 by -3% since 2006 mostly in North America. Allogeneic HSCT remains highest amongst the European WB region (increase 8%). The increase in activity was accompanied by an increase in team numbers from 1327 in 2006 to 1581 in 2015 but also by an increase of activity in the teams. Discussion: Autologous HSCT utilization has increased worldwide in high-income SDI WB region countries for MM yet has not increased proportionally amongst low-middle income WB regions. There is a disparity in autologous HSCT utilization amongst high-income regions, exceeding 20% in North America and Europe, while remaining poorly utilized in Africa and the East Mediterranean. Latin America has increased their utilization and is for the first time above 10%. However, we are limited with respect to use of incidence data in LMIC countries from the GBD, likely due to under reporting. Conflicting clinical trial data likely contributed to the decline in some regions for first allogeneic HSCT in MM. More work is needed to improve access to transplantation services for MM patients, especially in low to middle income countries. Conclusion: Although autologous HSCT numbers and rates have increased globally, there are marked disparities in usage amongst high versus low to middle income countries. More work is needed to improve access to HSCT for MM globally. Figure 1 Disclosures Cowan: Celgene: Consultancy, Research Funding; Cellectar: Consultancy; Juno: Research Funding; Sanofi: Consultancy; Abbvie: Research Funding; Janssen: Consultancy, Research Funding. Atsuta:Janssen Paharmaceutical K.K.: Honoraria; Kyowa Kirin Co., Ltd: Honoraria; Chugai Pharmaceutical Co., Ltd.: Honoraria; Mochida Pharmaceutical Co. Ltd: Honoraria. Worel:Sanofi Genzyme, Malinckrodt Therakos: Research Funding; Jazz, Sanofi, Celgene, Novartis, Malinckrodt Therakos: Honoraria; Sanofi Genzyme, Malinckrodt Therakos: Speakers Bureau. Libby:Alnylam: Consultancy; Abbvie: Consultancy; Pharmacyclics and Janssen: Consultancy; Akcea: Consultancy. Pasquini:Novartis: Research Funding; Kite Pharmaceuticals: Research Funding; BMS: Research Funding; Medigene: Consultancy; Amgen: Consultancy; Pfizer: Consultancy. Galeano:Szabo SA: Other: (Equity interest). Szer:Amgen: Honoraria, Other: Travel, Research Funding; Alexion: Honoraria, Other: Travel, Research Funding; Pfizer: Honoraria, Other: Travel, Research Funding; Sanofi: Honoraria, Other: Travel, Research Funding; Takeda: Honoraria, Other: Travel, Research Funding; Prevail Therapeutics: Honoraria, Other: Travel, Research Funding; Novartis: Honoraria, Other: Travel, Research Funding; MSD: Honoraria, Other: Travel, Research Funding; Celgene: Honoraria, Other: Travel, Research Funding. Kroeger:Neovii: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Riemser: Research Funding; JAZZ: Honoraria; Sanofi-Aventis: Honoraria; Novartis: Honoraria, Research Funding; Medac: Honoraria; DKMS: Research Funding. Weisdorf:Fate Therapeutics: Consultancy; Incyte: Research Funding; Pharmacyclics: Consultancy. Niederwieser:Cellectis: Consultancy; Daichii: Speakers Bureau.

Abstract John Guare distinguishes himself as a playwright who has represented New York City’s various neighborhoods and has fought realist conventions throughout his work. By relying on considerations advanced by Robert Bennett in his study of the literature, art, jazz and architecture of New York City after World War II, the current analysis shows that Guare approaches the discourse of the global capital of the world deconstructively, just like the post-war avant-garde he is probably familiar with. Moreover, Guare’s own search for experimental strategies reflects that of his predecessors and of the shape-shifting city itself. Included in a volume which is part of the Contemporary Dramatists series published by Methuen Drama, the four plays under discussion are: “The House of Blue Leaves” (1971), “Landscape of the Body” (1977), “Bosoms and Neglect” (1979, 1986) and “Six Degrees of Separation” (1990). Exploring the main characters’ experiences in New York City and their encounters with recognizable (or easily legible) sites of this quintessentially American metropolis, such as Greenwich Village and Central Park, the essay examines how Guare deconstructs urban space, advancing a most original and coherent reading of the city.

Abstract Long before Toni Morrison was extensively recognized as a serious contender in the “Global Market of Intellectuals,” she was obviously reading and absorbing challenging critical work that was considered “provocative and controversial” by the keepers of the US academic community at the time. While no one disputes the influence of Elaine Pagels’ work on Gnosticism at the University of Princeton, particularly its importance for Jazz and Paradise, the second and third novels of the Morrison trilogy, Gnosticism in Beloved has not been so carefully considered. Yet this keen interest in Gnosticism coupled with the author’s systematic study of authors from the mid-19th-century American Renaissance inevitably led her to deal with the fascination of Renaissance authors with Egypt (where the Nag Hammadi manuscripts were rediscovered), its ancient civilization, and its mythology. The extensive analysis of a leading French literary critic of Herman Melville, Prof. Viola Sachs, becomes the inspiration for a startlingly different reading of Morrison’s seminal novel, one that positions this author in a direct dialogue with the premises of Melville’s masterpiece, Moby-Dick, also drawing on the importance of Gnosticism for Umberto Eco’s 1980 international best-seller, The Name of the Rose.

AbstractThis article describes a specific history of technological mediation in the circulation of popular music by examining local practices of listening to recordings in Japanese kissaten (often shortened to kissa and meaning, loosely, ‘coffeehouse’). In postwar music kissaten, Japanese listeners were socialised to recordings of foreign music through new modes of hyper-attentive listening. While jazz kissa (though famous as crucibles for radical pro-democracy politics and the explosion of modern urban cool in post-war Japanese cities) encouraged local listeners to develop musical appreciation through the stylistic classification of distant recorded sources, later experimental music kissa helped forge unique local performance scenes by disturbing received modes of generic classification in favour of ‘Noise’. I recount the emergence of a genre called ‘Noise’ in the story of a 1970s Kyoto ‘free’ kissa Drugstore, whose countercultural clientele came to represent ‘Noise’ as a new musical style in its transnational circulation during the 1990s. This ethnographic history presents the music kissa as a complicated translocal site that articulates the cultural marginality of Japanese popular music reception in an uneven global production; but which also helps to develop virtuosic experimental practices of listening through which imported recordings are recontextualised, renamed and recreated.

Plant immune responses mediated by the hormone jasmonoyl-l-isoleucine (JA-Ile) are metabolically costly and often linked to reduced growth. Although it is known that JA-Ile activates defense responses by triggering the degradation of JASMONATE ZIM DOMAIN (JAZ) transcriptional repressor proteins, expansion of theJAZgene family in vascular plants has hampered efforts to understand how this hormone impacts growth and other physiological tasks over the course of ontogeny. Here, we combined mutations within the 13-memberArabidopsis JAZgene family to investigate the effects of chronic JAZ deficiency on growth, defense, and reproductive output. A higher-order mutant (jazdecuple,jazD) defective in 10JAZgenes (JAZ1–7,-9,-10, and-13) exhibited robust resistance to insect herbivores and fungal pathogens, which was accompanied by slow vegetative growth and poor reproductive performance. Metabolic phenotypes ofjazDdiscerned from global transcript and protein profiling were indicative of elevated carbon partitioning to amino acid-, protein-, and endoplasmic reticulum body-based defenses controlled by the JA-Ile and ethylene branches of immunity. Resource allocation to a strong defense sink injazDleaves was associated with increased respiration and hallmarks of carbon starvation but no overt changes in photosynthetic rate. Depletion of the remaining JAZ repressors injazDfurther exaggerated growth stunting, nearly abolished seed production and, under extreme conditions, caused spreading necrotic lesions and tissue death. Our results demonstrate that JAZ proteins promote growth and reproductive success at least in part by preventing catastrophic metabolic effects of an unrestrained immune response.

Abstract AML blasts harbor multiple genomic, epigenomic, and transcriptomic abnormalities. Proteins are responsible for much of the functional biology derived from these transforming events, yet few studies have examined the global proteome in specimens from AML patients. To gain insight into the biology and prognostic biomarkers for AML, we examined the genome, transcriptome and proteome in highly enriched less differentiated, viable leukemic blasts (VLBs) from previously untreated patients with NPM1 mutated (NPM1+) AML. We focused on NPM1+ AML because 1) NPM1 mutations are the most common genomic abnormality used for risk stratifying AML patients; 2) clinical outcomes for NPM1+ patients vary substantially; and 3) restricting studies to VLBs from patients with NPM1+ AMLreduces the molecular diversity and confounding interactions that may impede identification of biological and clinically relevant biomarkers. Cryopreserved specimens from patients with NPM1+ AML were obtained from the SWOG Leukemia and Fred Hutch/University of Washington Hematopoietic Disease Repositories (N=178). All patients were treated with dose intensive induction and consolidation with curative intent. VLBs were isolated from specimens using fluorescence-activated cell sorting (FACS). Fragment analysis was used to identify FLT3-ITDs, while other genomic mutations were identified using targeted next generation sequencing (NGS). RNA sequencing (RNAseq) was used to quantify transcript expression, while protein expression was quantified using tandem mass tag labelling followed by liquid chromatograph with tandem mass spectrometry (TMT-LC-MS/MS). Prognostic significance of biomarkers was examined by univariate and multivariate analyses, with the later adjusting for both age and ELN2017 risk. Adequate analyte from VLBs were available for RNAseq and TMT-LC-MS/MS studies in 131 and 71 patients, respectively. Proteomic profiling identified 6712 expressed proteins. Multivariable analyses adjusting for age and ELN2017 risk identified 211, 218, and 313 proteins were significantly associated with CR, EFS, and OS, respectively, of which 116 and 174 had a HR ≥ 2 or ≤ 0.5 for EFS and OS (Fig 1A). Analyses showed an overall modest correlation between RNA and protein expression for the 6297 genes present in both RNA and protein datasets (Fig 1B, R =0.27). A total of 163 of the 174 proteomic candidates for OS had RNAseq data, but RNA expression was not significantly correlated with OS for most of these genes (Fig 1C). Similarly, the expression correlation between RNA and protein was not improved by restricting the analyses to these 163 genes (Fig 1D, R =0.28). We also compared protein expression between the NPM1+ VLBs and CD34 progenitors from healthy donors (NLCD34=5), which identified 747 proteins with significant expression differences between the two cell populations (FDR ≤ 0.1). Seventy-three of the 747 proteins displayed &gt; 3-fold increased expression in NPM1+ VLBs, some of which activate targetable pathways (HOMER-&gt;WNT/CTNNB1) and/or amenable to adoptive immunotherapies (e.g., CT45). Additional analyses identified 401 proteins with significantly increased expression in VLBs harboring a high FLT3-ITD allelic ratio (NPM1+/FLT3-ITD-H), a less favorable population of patients. In these less favorable patients, many of the same proteins remained overexpressed (e.g., CT45 with 7.85-fold increased expression, FDR=0.009), but other targetable proteins also emerged. For example, PKCD had a 3.41-fold increased expression (FDR=0.001) in the NPM1+/FLT3-ITD-H VLBs, and targetable inhibitors against this protein (e.g., Parsaclisib) are already in clinical trials for other cancers. This study examines for the first time the global proteome in a large number of VLBs from patients with AML. As with recent publications examining other cancers, the overall expression correlation between RNA and protein was modest, at best, and most of the informative prognostic proteins for OS were not significant in the transcriptome. In addition, the results show the potential to identify novel proteomic targets in subpopulations of AML patients, which may not be otherwise discovered using other means. Thus, the results demonstrate the need to include proteomic profiling in future multi-omics studies seeking to discover novel prognostic biomarkers and therapeutic targets. Figure 1 Figure 1. Disclosures Erba: AbbVie Inc; Agios Pharmaceuticals Inc; Bristol Myers Squibb; Celgene, a Bristol Myers Squibb company; Incyte Corporation; Jazz Pharmaceuticals Inc; Novartis: Speakers Bureau; AbbVie Inc: Other: Independent review committee; AbbVie Inc; Agios Pharmaceuticals Inc; ALX Oncology; Amgen Inc; Daiichi Sankyo Inc; FORMA Therapeutics; Forty Seven Inc; Gilead Sciences Inc; GlycoMimetics Inc; ImmunoGen Inc; Jazz Pharmaceuticals Inc; MacroGenics Inc; Novartis; PTC Therapeutics: Research Funding; AbbVie Inc; Agios Pharmaceuticals Inc; Astellas; Bristol Myers Squibb; Celgene, a Bristol Myers Squibb company; Daiichi Sankyo Inc; Genentech, a member of the Roche Group; GlycoMimetics Inc; Incyte Corporation; Jazz Pharmaceuticals Inc; Kura Oncology; Nov: Other: Advisory Committee. Moseley: BioSight Ltd: Consultancy. Radich: Novartis: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees.

Modern ethnic music, represented by a wide palette of styles and trends, is an interesting global musical phenomenon, based on the actualization of national musical traditions and building intercultural dialogue. In this article, we clarify the terminological apparatus and conceptual environment of ethnic music, which in Russian realities is understood as a part of contemporary culture that combines traditional music and folk music, as well as consider the socio-cultural prerequisites for the emergence of this phenomenon and the main tendencies of ethnic music. Born as a youth folklore movement, based on a search for new sources of inspiration for young musicians and composers, today the phenomenon of ethnic music presents a rich palette in contemporary music space. These directions, formed by merging elements of different national musical traditions, synthesizing different musical styles or combining different methods, have at their core the main component — traditional musical folklore, which is embodied in new modern forms, reinterpreted and interpreted by ethnic musicians. Thus, a rich corpus of folk music culture is preserved and actualized. Among the main directions of ethnic music, we distinguish: musical folklore; folk music; ethno-fusion; new age; ethno-jazz; ethno-electronics, including folk-rock, pop-folk, folk-house and other movements based on the synthesis of musical folklore and current musical styles.

In Italy, the counterculture of the Sixties lasted until 1979, when it perished in the clash between two paranoias: the Italian state’s fear of terrorism and the radical social movements from which it arose, and the terrorists’ fear of the state’s authoritarianism. Popular musicians were trapped between these paranoias, and their music searches to escape from both while chronicling the closing of the space between them, the only space in which countercultural social and artistic experimentation could take place. This essay focuses on the Italian “international POPular group” Area, which acted, in opposition to the generalized paranoia of the period, as a switching station linking progressive rock, electronic music, free jazz, global indigenous music, Fluxus sound experiments and postmodernist poetics with anti-militarist, anti-racist, socialist-feminist politics independent of the existing political party system. To create those links, the band was compelled to subvert the conventions of pop music from within and to move beyond pop’s traditional boundaries into unstructured improvisation and avant-garde formal exploration. Area singer Demetrio Stratos’s death in 1979 coincided with the Italian state’s final crackdown on terrorism and the counterculture and marked the end of the richest countercultural experiment on earth, which still has much to teach us.

The objective of the paper is to define long-term trends and factors in the development of the world energy industry and their refraction to Ukrainian realities. The article consists of an introduction, three sections, namely: the main trends in the development of the global fuel and energy complex, analysis of the current state, long-term trends and factors in the development of the national fuel and energy complex of Ukraine. Conclusions end the paper. As for the world energy sector it is shown that its modern changes – Grand Transit – are due to the ideology of sustainable development and have the character of an extraordinary change in the technocenosis, the transition from the use of fossil fuels to energy from renewable sources, mainly – wind and photovoltaic nature. Along with the major tendencies of the Great Transition, there is also the trilemization and politicization of energy sector. Trilemization components are: Energy Security, Energy Equity and Environmental Sustainability. There are three scenarios for the development of the global energy – Unfinished Symphony, Modern Jazz and Hardrock, distinguished by the degree of greening and the availability of energy resources. Political motives are becoming more and more significant at all levels – from global to local. Major players are lobbying their interests, there is an activity of structures from the field of nuclear energy, powerful fuel companies, owners of gas transportation and gas distribution infrastructure. In Ukraine, transformation processes are taking place against the backdrop of low environmental acceptability and high depreciation of fuel and energy sector facilities and infrastructure, political and economic instability. The requirements of decarbonization create challenges to the very existence of coal energy, which is the main component of the energy generating fund of the country and the regions, where mines are located. Options for the development of hydrogen/ammonia energy in the form of vertically integrated energy-chemical systems with the nuclear power plants and reformed coal-fired thermal power plants are considered as promising; energy diversification of mining regions; the creation of virtual power plants based on hydrodynamic water heating installations.

Abstract BACKGROUND: Despite improvements in the treatment of "unfit or older" AML patients with the combination of azacitidine (AZA) and venetoclax (VEN), long-term survival for these patients remains poor. Additions to this new regimen may further improve patient outcomes. Overexpression of CD123, the alpha subunit of the IL-3 receptor, is seen in AML blasts. IMGN632 is a CD123-targeting antibody-drug conjugate (ADC) comprised of a high-affinity anti-CD123 antibody coupled to a DNA-alkylating payload of the novel IGN (indolinobenzodiazepine pseudodimer) class. Preclinical data have demonstrated synergy between IMGN632 and AZA and/or VEN, including overcoming AZA/VEN resistance in murine AML models (Kuruvilla ASH 2020), supporting the clinical exploration of these combinations. Doublets of IMGN632 with both AZA and VEN were studied in AML patients and supported testing of the triplet of IMGN632, AZA, and VEN. Here we report the initial safety and anti-leukemia activity findings from this novel triplet. METHODS: This Phase 1b/2 study was designed to determine the safety, tolerability, and preliminary anti-leukemic activity of IMGN632 combined with AZA and VEN in patients with CD123-positive AML. To date, the triplet combination escalation consists of 5 cohorts of IMGN632 plus AZA and VEN, each agent designated by "C" for IMGN632 dose in mcg/kg, "A" for AZA dose in mg/m2 x7 days, or "V" for VEN # of days at 400mg QD. Four cohorts dosed IMGN632 on Day 7 of each cycle (C15A50V8, C15A50V14, C15A75V21, C45A50V8), and one cohort dosed IMGN632 on Day 1 of each cycle (Day 1 C15A50V14). Responses are determined using modified ELN criteria with a 14-day count recovery window. RESULTS: At the time of this analysis, preliminary safety data are available for 35 relapsed or refractory (R/R) AML patients. The median age was 69y, 23% had secondary AML, 86% received prior intensive therapies, 37% that were refractory to first line therapy, and 51% had received prior VEN. Twenty-three percent of patients had FLT3 mutations. The toxicity profile was manageable in this R/R AML population with multiple prior therapies. The most common treatment emergent adverse events (TEAE) all grades [grade 3+ events] seen in &gt;20% of patients were infusion-related reactions (IRR, 37% [3%]), febrile neutropenia (26% [23%]), hypophosphatemia (26% [3%]), dyspnea (26% [6%]), pneumonia (20% [14%]), and fatigue (20% [0%]). One patient in the Day 1 C15A50V14 cohort discontinued IMGN632 due to a TEAE (DLT IRR, resolved). Cytopenias and infections were consistent with those observed with the AZA+VEN regimen in this R/R population. No TLS, VOD, capillary leak or cytokine release were observed. 30-day mortality was 0%. Efficacy was seen across all cohorts/doses and schedules (efficacy evaluable population, n=29). The objective response rate (ORR) was 55% with a composite complete remission (CCR) rate of 31% (1 CR, 4 CRh, 2 CRp, 2 CRi). Higher intensity cohorts (IMGN632 dose 45 mcg/kg or 14-21 days of VEN) on the Day 7 schedule (n=20) were associated with higher response rates: ORR 75%, CCR rate 40% (Figure 1). At these higher intensity cohorts, in the VEN naïve subset (n=10), ORR/CCR rates were 100%/60%, respectively. Significant activity was also seen in the FLT3 mutant subset (n=7), with ORR/CCR rates of 100%/71%. CONCLUSION: With a manageable safety profile in this R/R AML population, the novel IMGN632 triplet demonstrated compelling anti-leukemia activity. Ongoing escalation cohorts aim to optimize safety and efficacy of the triplet therapy. Expansion proof-of-concept cohorts are planned in both relapsed and frontline AML patients (NCT04086264). Updated safety, efficacy, and PK data will be presented. Figure 1 Figure 1. Disclosures Daver: Trillium: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Sevier: Consultancy, Research Funding; Glycomimetics: Research Funding; ImmunoGen: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Novimmune: Research Funding; Gilead Sciences, Inc.: Consultancy, Research Funding; Hanmi: Research Funding; Amgen: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding; FATE Therapeutics: Research Funding; Trovagene: Consultancy, Research Funding; Novartis: Consultancy; Pfizer: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy, Other: Data Monitoring Committee member; Dava Oncology (Arog): Consultancy; Celgene: Consultancy; Syndax: Consultancy; Shattuck Labs: Consultancy; Agios: Consultancy; Kite Pharmaceuticals: Consultancy; SOBI: Consultancy; STAR Therapeutics: Consultancy; Karyopharm: Research Funding; Newave: Research Funding. Aribi: Seagen: Consultancy. Montesinos: Teva: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Glycomimetics: Consultancy; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Tolero Pharmaceutical: Consultancy; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Stemline/Menarini: Consultancy; Forma Therapeutics: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Agios: Consultancy; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Astellas Pharma, Inc.: Consultancy, Honoraria, Other: Advisory board, Research Funding, Speakers Bureau. Roboz: Astex: Consultancy; Jazz: Consultancy; Glaxo SmithKline: Consultancy; Mesoblast: Consultancy; Blueprint Medicines: Consultancy; AstraZeneca: Consultancy; Bayer: Consultancy; Daiichi Sankyo: Consultancy; Amgen: Consultancy; MEI Pharma - IDMC Chair: Consultancy; Astellas: Consultancy; Agios: Consultancy; Actinium: Consultancy; AbbVie: Consultancy; Janssen: Research Funding; Jasper Therapeutics: Consultancy; Celgene: Consultancy; Helsinn: Consultancy; Janssen: Consultancy; Bristol Myers Squibb: Consultancy; Novartis: Consultancy; Otsuka: Consultancy; Pfizer: Consultancy; Roche/Genentech: Consultancy. Wang: Jazz Pharmaceuticals: Consultancy, Honoraria, Other: Advisory Board; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Other: Advisory Board, Speakers Bureau; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Stemline Therapeutics: Consultancy, Honoraria, Other: Advisory board, Speakers Bureau; Kura Oncology: Consultancy, Honoraria, Other: Advisory board, steering committee, Speakers Bureau; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Mana Therapeutics: Consultancy, Honoraria; GlaxoSmithKline: Consultancy, Honoraria, Other: Advisory Board; Novartis: Consultancy, Honoraria, Other: Advisory Board; Kite Pharmaceuticals: Consultancy, Honoraria, Other: Advisory Board; Genentech: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Other: Advisory board; DAVA Oncology: Consultancy, Speakers Bureau; Rafael Pharmaceuticals: Other: Data safety monitoring committee; Gilead: Consultancy, Honoraria, Other: Advisory board; Daiichi Sankyo: Consultancy, Honoraria, Other: Advisory board; PTC Therapeutics: Consultancy, Honoraria, Other: Advisory board; Genentech: Consultancy; MacroGenics: Consultancy. Walter: Agios Pharmaceuticals, Inc.: Consultancy, Research Funding; Amgen, Inc.: Consultancy, Research Funding; Amphivena Therapeutics, Inc.: Current equity holder in publicly-traded company; Aptevo Therapeutics, Inc.: Consultancy, Research Funding; Arog Pharmaceuticals, Inc.: Research Funding; Astellas Pharma US, Inc.: Consultancy; BioLineRx, Ltd.: Consultancy, Research Funding; Boston Biomedical, Inc.: Consultancy; Bristol Myers Squibb, Inc.: Consultancy; Celgene, Inc.: Consultancy, Research Funding; Genentech, Inc.: Consultancy; GlaxoSmithKline, Inc.: Consultancy; ImmunoGen, Inc.: Research Funding; Janssen Global Services, LLC: Consultancy; Janssen Research & Development, Inc.: Research Funding; Jazz Pharmaceuticals, Inc.: Consultancy, Research Funding; Kite Pharma, Inc.: Consultancy; Kronos Bio, Inc.: Consultancy; Kura Oncology, Inc.: Research Funding; Macrogenics, Inc.: Research Funding; New Link Genetics: Consultancy; Pfizer, Inc.: Consultancy, Research Funding; Race Oncology Ltd.: Consultancy; Selvita: Research Funding; Stemline Therapeutics, Inc.: Research Funding. Jeyakumar: Jazz: Research Funding; Pfizer: Research Funding. DeAngelo: Abbvie: Research Funding; Blueprint Medicines Corporation: Consultancy; Incyte Corporation: Consultancy; Forty-Seven: Consultancy; Autolus: Consultancy; Agios: Consultancy; Amgen: Consultancy; GlycoMimetics: Research Funding; Shire: Consultancy; Takeda: Consultancy; Novartis: Consultancy, Research Funding; Pfizer: Consultancy; Jazz: Consultancy. Erba: Celgene: Membership on an entity's Board of Directors or advisory committees; AbbVie, Agios, Amgen, Astellas Pharma, Celgene, Daiichi Sankyo, Glycomimetics, ImmunoGen, Incyte, Jazz Pharmaceuticals, MacroGenics, Novartis, and Pfizer: Consultancy; Glycomimetics: Membership on an entity's Board of Directors or advisory committees; Covance (AbbVie): Other: Independent Review Committee ; AbbVie, Agios, Celgene, Incyte, Jazz Pharmaceuticals, and Novartis: Speakers Bureau; AbbVie, Daiichi Sankyo, Forma, ImmunoGen, Jazz Pharmaceuticals, MacroGenics, Novartis, and PTC: Research Funding. Advani: Abbvie: Research Funding; Immunogen: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Research Funding; OBI: Research Funding; Glycomimetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Macrogenics: Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding. Martinelli: Celgene /BMS: Consultancy, Speakers Bureau; Stemline Therapeutics: Consultancy; Roche: Consultancy; Jazz Pharmaceuticals: Consultancy; Pfizer: Consultancy, Speakers Bureau; Abbvie: Consultancy; Daichii Sankyo: Consultancy; Incyte: Consultancy; Astellas: Consultancy, Speakers Bureau. Gastaud: PFIZER: Consultancy; CELGENE/BMS: Consultancy; ABBVIE: Consultancy; GSK: Consultancy. Altman: Biosight: Membership on an entity's Board of Directors or advisory committees, Other: reimbursement for travel, Research Funding; ImmunoGen: Research Funding; Kartos Therapeutics: Research Funding; Kura Oncology: Membership on an entity's Board of Directors or advisory committees, Research Funding; Fujifilm: Research Funding; Glycomimetics: Other: data monitoring committee; Loxo: Research Funding; Celgene: Research Funding; Boehringer Ingelheim: Research Funding; Astellas: Honoraria, Research Funding; Aptos: Research Funding; Aprea: Research Funding; Amgen: Research Funding; Abbvie: Honoraria, Research Funding; ALX Oncology Inc.: Research Funding; Syros: Membership on an entity's Board of Directors or advisory committees. de la Fuente: Incyte: Consultancy, Speakers Bureau; Abbie: Consultancy, Speakers Bureau; Novartis: Research Funding; BMS: Consultancy, Speakers Bureau. Gaidano: Incyte: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; Astrazeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Curti: Jazz Pharma: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees. Boissel: PFIZER: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; CELGENE: Honoraria; Bristol-Myers Squibb: Honoraria, Research Funding; SANOFI: Honoraria; Servier: Consultancy, Honoraria; Incyte: Honoraria; JAZZ Pharma: Honoraria, Research Funding. Recher: Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Macrogenics: Honoraria, Membership on an entity's Board of Directors or advisory committees; MaatPharma: Research Funding; Jazz: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria; Incyte: Honoraria; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS/Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Agios: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Schliemann: Philogen S.p.A.: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Other: travel grants; Astellas: Consultancy; AstraZeneca: Consultancy; Boehringer-Ingelheim: Research Funding; BMS: Consultancy, Other: travel grants; Jazz Pharmaceuticals: Consultancy, Research Funding; Novartis: Consultancy; Roche: Consultancy; Pfizer: Consultancy. Konopleva: Cellectis: Other: grant support; Calithera: Other: grant support, Research Funding; F. Hoffmann-La Roche: Consultancy, Honoraria, Other: grant support; Forty Seven: Other: grant support, Research Funding; Agios: Other: grant support, Research Funding; Ablynx: Other: grant support, Research Funding; Genentech: Consultancy, Honoraria, Other: grant support, Research Funding; KisoJi: Research Funding; Ascentage: Other: grant support, Research Funding; Eli Lilly: Patents & Royalties: intellectual property rights, Research Funding; Reata Pharmaceuticals: Current holder of stock options in a privately-held company, Patents & Royalties: intellectual property rights; Novartis: Other: research funding pending, Patents & Royalties: intellectual property rights; AstraZeneca: Other: grant support, Research Funding; Rafael Pharmaceuticals: Other: grant support, Research Funding; Sanofi: Other: grant support, Research Funding; Stemline Therapeutics: Research Funding; AbbVie: Consultancy, Honoraria, Other: Grant Support, Research Funding. Sallman: Takeda: Consultancy; AbbVie: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; Aprea: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shattuck Labs: Membership on an entity's Board of Directors or advisory committees; Incyte: Speakers Bureau; Kite: Membership on an entity's Board of Directors or advisory committees; Syndax: Membership on an entity's Board of Directors or advisory committees; Intellia: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Magenta: Consultancy. Marcucci: Novartis: Other: Speaker and advisory scientific board meetings; Agios: Other: Speaker and advisory scientific board meetings; Abbvie: Other: Speaker and advisory scientific board meetings. Kantarjian: KAHR Medical Ltd: Honoraria; Ipsen Pharmaceuticals: Honoraria; Immunogen: Research Funding; Jazz: Research Funding; Ascentage: Research Funding; Novartis: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; NOVA Research: Honoraria; Pfizer: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; BMS: Research Funding; Daiichi-Sankyo: Research Funding; Astra Zeneca: Honoraria; Aptitude Health: Honoraria; Astellas Health: Honoraria; Taiho Pharmaceutical Canada: Honoraria; Precision Biosciences: Honoraria. Malcolm: Immunogen: Current Employment. Zweidler-McKay: ImmunoGen: Current Employment. Sweet: Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; AROG: Membership on an entity's Board of Directors or advisory committees; Bristol Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Abstract BACKGROUND Tisagenlecleucel is an FDA approved chimeric antigen receptor (CAR)-T cell therapy that reprograms T cells to eliminate CD19+ B cells. ELIANA (NCT02435849) is a phase 2 pivotal study of tisagenlecleucel in pediatric/young adult patients (pts) with CD19+ r/r B-cell acute lymphoblastic leukemia (ALL), the first global trial of a CAR-T cell therapy. The primary objective was met, with an overall remission rate (ORR) of 81% (complete remission [CR] + CR with incomplete blood count recovery [CRi]). Here we present an update of ELIANA, with additional pts and additional 11 mo follow-up from the previous report (Maude et al. N Engl J Med 2018). METHODS Eligible pts were aged ≥3 y at screening and ≤21 y at diagnosis and had ≥5% leukemic blasts in bone marrow. Tisagenlecleucel was centrally manufactured at 2 sites (Morris Plains, NJ, USA and Leipzig, Germany) by lentiviral transduction of autologous T cells with a vector encoding for a second generation 4-1BB anti-CD19 CAR and expanded ex vivo. Tisagenlecleucel was provided to pts at 25 study centers in 11 countries on 4 continents using cryopreserved apheresed mononuclear cells, central production facilities, and a global supply chain. The primary endpoint, ORR within 3 mo and maintained for ≥28 d among infused pts, was assessed by an independent review committee. Secondary endpoints included duration of remission (DOR), overall survival (OS), safety, and cellular kinetics. RESULTS As of April 13, 2018, 113 pts were screened and 97 enrolled. There were 8 manufacturing failures (8%) and 10 pts (10%) were not infused due to death or adverse events (AEs). Following lymphodepleting chemotherapy in most pts (76/79; fludarabine/cyclophosphamide [n=75]), 79 pts were infused with a single dose of tisagenlecleucel (median dose, 3.0×106 [range, 0.2-5.4×106] CAR-positive viable T cells/kg), and all had ≥3 mo of follow-up or discontinued earlier (median time from infusion to data cutoff, 24 mo [range, 4.5-35 mo]). Median age was 11 y (range, 3-24 y); 61% of pts had prior hematopoietic stem cell transplant (SCT). Among the 65 pts with CR/CRi, 64 (98%) were MRD- within 3 mo. Median DOR by K-M analysis was not reached (Figure): responses were ongoing in 29 pts (max DOR, 29 mo and ongoing); 19 pts relapsed before receiving additional anticancer therapy (13 died subsequently); 8 pts underwent SCT while in remission, 8 received additional anticancer therapy (non-SCT) and 1 discontinued while in remission. The probability of relapse-free survival at 18 mo was 66% (95% CI, 52%-77%). Median OS was not reached; OS probability at 18 mo was 70% (95% CI, 58%-79%). Cytokine release syndrome (CRS) occurred in 77% of pts (grade [G] 3/4; 48%; graded using the Penn scale); 39% of pts received tocilizumab for treatment of CRS with or without other anti-cytokine therapies; 48% of pts required ICU-level care for CRS, with a median ICU stay of 7 d. All cases of CRS were reversible. Most common G 3/4 nonhematologic AEs (>15%) other than CRS were neutropenia with a body temperature >38.3°C (62% within 8 wk of infusion), hypoxia (20%), and hypotension (20%). 13% of pts experienced G 3 neurological events, with no G 4 events or cerebral edema. Based on laboratory results, 43% and 54% of pts had G 3/4 thrombocytopenia and neutropenia not resolved by d 28; the majority of events resolved to G ≤2 by 3 mo. 25 post-infusion deaths were reported: 2 within 30 d (1 disease progression, 1 cerebral hemorrhage); 23 after 30 d of infusion (range, 53-859 d; 18 disease progression, 1 each due to encephalitis, systemic mycosis, VOD [hepatobiliary disorders related to allogeneic-SCT], bacterial lung infection, and an unknown reason after study withdrawal). Tisagenlecleucel expansion in vivo correlated with CRS severity, and persistence of tisagenlecleucel along with B-cell aplasia in peripheral blood was observed for ≥2.5 y in some responding pts. Analysis of B-cell recovery and correlation with relapse will be presented. CONCLUSIONS With longer follow-up, the ELIANA study continues to confirm the efficacy of a single infusion of tisagenlecleucel in pediatric and young adults with ALL without additional therapy. AEs were effectively and reproducibly managed globally by appropriately trained personnel at study sites. The achievement of high overall response rates and deep remissions, in combination with the median duration of response and overall survival not being reached, further corroborate previously reported results. Figure. Figure. Disclosures Grupp: Novartis Pharmaceuticals Corporation: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy; Adaptimmune: Consultancy; University of Pennsylvania: Patents & Royalties. Maude:Novartis Pharmaceuticals Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees. Rives:Shire: Consultancy, Other: Symposia, advisory boards ; Jazz Pharma: Consultancy, Other: Symposia, advisory boards ; Novartis Pharmaceuticals Corporation: Consultancy, Other: Symposia, advisory boards ; Amgen: Consultancy, Other: advisory board . Baruchel:Celgene: Consultancy; Amgen: Consultancy; Roche: Consultancy; Jazz Pharmaceuticals: Consultancy, Honoraria, Other: Travel, accommodations or expenses; Novartis: Membership on an entity's Board of Directors or advisory committees; Shire: Research Funding; Servier: Consultancy. Bittencourt:Novartis Pharmaceuticals Corporation: Consultancy; Jazz Pharmaceuticals: Consultancy, Honoraria. Bader:Riemser: Research Funding; Cellgene: Consultancy; Medac: Patents & Royalties, Research Funding; Neovii: Research Funding; Novartis: Consultancy, Speakers Bureau. Laetsch:Bayer: Consultancy; Pfizer: Equity Ownership; Eli Lilly: Consultancy; Novartis Pharmaceuticals Corporation: Consultancy; Loxo Oncology: Consultancy. Stefanski:Novartis Pharmaceuticals Corporation: Consultancy, Honoraria, Speakers Bureau. Myers:Novartis Pharmaceuticals Corporation: Consultancy, Honoraria, Research Funding, Speakers Bureau. Qayed:Novartis: Consultancy. Pulsipher:CSL Behring: Consultancy; Amgen: Honoraria; Adaptive Biotech: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Speakers Bureau. Martin:Novartis Pharmaceuticals Corporation: Research Funding; Jazz Pharmaceuticals: Research Funding. Nemecek:Novartis Pharmaceuticals Corporation: Other: advisory boards. Boissel:Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees. Leung:Novartis Pharmaceuticals Corporation: Employment. Eldjerou:Novartis Pharmaceuticals Corporation: Employment. Yi:Novartis Pharmaceuticals Corporation: Employment. Mueller:Novartis Institutes for Biomedical Research: Employment; Novartis Pharmaceuticals Corporation: Equity Ownership, Other: Patent pending. Bleickardt:Novartis Pharmaceuticals Corporation: Employment.

The use of fossil fuels as the main source of energy for most countries has caused several negative environmental impacts, such as global warming and air pollution. Air pollution causes many health problems, causing social and economic negative effects. Worldwide efforts are being made to avoid global warming consequences through the establishment of international agreements that then lead to local policies adapted to the development of each signing nation. In addition, there is a depletion of nonrenewable resources which may be scarce or nonexistent in future generations. The preservation of resources, which is a common goal of the Circular Economy strategy and of sustainable development, is not being accomplished nowadays. In this work, the calculation of indicators and mathematical and statistical analysis were applied to clarify and evidence the trends, provide information for the decision-making process, and increase public awareness. The fact that European countries do not possess abundant reserves of fossil fuels will not change, but the results of this analysis can evolve in the future. In this work, fossil fuel energy consumption, fossil fuel depletion, and their relationship with other variables, such as energy dependence and share of renewable energy in gross final energy consumption, were analyzed for 29 European countries. Furthermore, it was possible to conclude that many European countries still depend heavily on fossil fuels. Significant differences were not found in what concerns gross inland consumption per capita when the Kruskal–Wallis test was applied. It was possible to estimate that by 2050 (considering Jazz scenario) it will only remain approximately 14% of oil proven reserves, 72% of coal proven reserves and 18% of gas proven reserves. Given the small reserves of European countries on fossil fuels, if they need to use them, they will fast disappear.