Journal articles on the topic 'Solel Boneh International Group'

Importance Osteoporosis causes increased morbidity and mortality, and thus poses a significant economic burden to the health systems worldwide. Objective The aim of this study was to review and compare the most recently published major guidelines on diagnosis and management of this common medical entity. Evidence Acquisition A thorough comparative review of the most influential guidelines from the RACGP (Royal Australian College of General Practitioners), the ESCEO-IOF (European Society for Clinical and Economic Aspects of Osteoporosis–International Osteoporosis Foundation), the NOGG (National Osteoporosis Guideline Group), the NAMS (North American Menopause Society), the ES (Endocrine Society), and the ACOG (American College of Obstetricians and Gynecologists) was conducted. Results The reviewed guidelines generally agree on the definition, the criteria, and investigations used to diagnose osteoporosis. They also concur regarding the risk factors for osteoporosis and the suggested lifestyle modifications (calcium and vitamin D intake, normal body weight, reduction of alcohol consumption, and smoking cessation). However, there is lack of consensus on indications for fracture risk assessment in the general population and the exact indications for bone mineral density assessment. Referral to a bone specialist is reserved for complex cases of osteoporosis (NOGG, NAMS, and ACOG) or in case of inadequate access to care (RACGP). The use of hip protectors to reduce the risk of fractures is supported by RACGP, NOGG, and NAMS, solely for high-risk elderly patients in residential care settings. All guidelines reviewed recognize the efficacy of the pharmacologic agents (ie, bisphosphonates, denosumab, hormone therapy, and parathyroid hormone analogs). Nonetheless, recommendations regarding monitoring of pharmacotherapy differ, primarily in the case of bisphosphonates. The proposed intervals of repeat bone mineral density testing after initiation of drug therapy are set at 2 years (RACGP), 1–3 years (NAMS, ES, and ACOG), or 3–5 years (ESCEO-IOF and NOGG). All guidelines agree upon the restricted use of bone turnover markers only in bone specialist centers for treatment monitoring purposes. Finally, the definition of treatment failure varies among the reviewed guidelines. Conclusions Osteoporosis is a distressing condition for women, mainly those of postmenopausal age. Thus, it seems of paramount importance to develop consistent international practice protocols for more cost-effective diagnostic and management techniques, in order to improve women's quality of life. Target Audience Obstetricians and gynecologists, family physicians. Learning Objectives After participating in this activity, the physician should be able to identify early risk factors for osteoporosis; describe the appropriate diagnostic techniques for osteoporosis; and explain available drug agents for the management of osteoporosis, as well as the difference in approach regarding their use.

Background: Clonal hematopoiesis of indeterminate potential (CHIP) is a clinically defined entity that is recognized by the 2022 International Consensus Classification and the 5 th Edition of the WHO. While the Clonal Hematopoiesis Risk Score (CHRS) incorporates 8 variables that underlie a prognostic framework for prediction of risk for progression to myeloid neoplasm (MN) (Weeks LD et al., NEJM Evidence 2023), there remains debate as to the role of mutations in epigenetic regulators, such as DNMT3A, TET2 and ASXL1 (“DTA”), with respect to clinical outcomes in the real-world setting. Although DTA mutations often occur early in myeloid pathogenesis, the persistence of these mutations as age-related clonal hematopoiesis (CH) might not significantly influence clinical course (Jongen-Lavrencic M et al., NEJM 2018). We have previously observed impaired clearance of DTA-mutant clones with hypomethylating agent or intensive chemotherapy for myelodysplastic neoplasms and acute myeloid leukemia (ASH abstract 4122; Blood (2022) 140 (Supplement 1): 9150-9151), and we now seek to understand the impact of sole DTA mutations in patients with CH. Methods: We studied a pre-selected group of patients who had an indication for undergoing bone marrow evaluation. Such indications included cytopenia(s), elevated blood cell count(s), staging/workup for lymphoma, and radiographic marrow abnormalities. Patients with CH were identified via concurrent morphologic, cytogenetic, and molecular diagnostics of bone marrow aspirates reviewed by UMass and Stanford Hematopathology from 2013 to 2023. CH was defined as presence of a somatic mutation with variant allele frequency (VAF) ≥ 2% on molecular diagnostics or non-myelodysplastic syndrome (MDS)-defining clonal cytogenetic aberration in a patient without morphologic evidence of MN. A total of 79 patients with CH were identified, then segregated based on presence or absence of sole DTA mutations. Results: We assessed the clinical trajectory of patients with CH who did not exclusively have DTA mutations (“non-sole DTA;” n = 58) (Panel A) compared to patients with CH who had DTA mutations alone without any other concurrent mutations (“sole DTA;” n = 21) (Panel B). The median age at detection of CH for sole DTA vs. non-sole DTA was 71.0 ± 2.11 years vs. 71.5 ± 1.45 years, respectively ( p = 0.454). Median number of mutations for sole DTA vs. non-sole DTA patients was 1.24 ± 1.2 vs. 2.24 ± 0.18, respectively ( p < 0.0001). Median follow-up for all patients was 450 days, and the median overall survival was not reached for either group. For non-sole DTA patients, 44 of 58 patients (76%) did not progress, while 14 of 58 patients (24%) progressed to frank MN at the time of analysis. Types of frank MN in the 14 progressors included MDS (50%), MDS/myeloproliferative neoplasm (MPN) overlap (28.6%), AML (14.3%), and MPN (7.1%). For sole DTA patients, 0 of 21 patients (0%) progressed. Regarding distribution of VAFs for sole DTA patients vs. non-sole DTA patients, mean VAF was 13.5% ± 1.91% vs. 31.6% ± 2.18%, respectively ( p < 0.001). For patients with both DTA mutations plus additional mutations, mean VAF for non-progressors vs. progressors was 30.4% ±1.47% vs. 38.6% ± 2.97%, respectively ( p = 0.206). For patients without any DTA mutations but with other somatic mutations, mean VAF for non-progressors vs. progressors was 29.7% ±1.67% vs. 35.2% ± 2.26%, respectively ( p = 0.160). Conclusion: In this study of pre-selected patients with CH, DTA mutations alone were insufficient for progression to frank MN. Progressors included patients with either (1) DTA mutations plus concurrent mutations, or (2) patients without DTA mutations but presence of mutations in other gene clusters. The clinical trajectory of patients with CH in our study differs from that of patients from large consortia possibly because our patients presented with an indication for testing, reflecting real-world data. A limitation of our analysis is the variability in time to recognition and diagnosis of CH, which reflects the high heterogeneity of these patients. Still, our data suggest the need for large-scale studies in the real-world setting to better prognosticate the relevance of DTA mutations for this patient population.

Systemic mastocytosis (SM) is a rare clonal hematologic neoplasm, driven, in almost all cases, by the activating KIT D816V mutation that leads to the growth and accumulation of neoplastic mast cells. While patients with advanced forms of SM have a poor prognosis, the introduction of KIT inhibitors (e.g., midostaurin, and avapritinib) has changed their outlook. Because of the heterogenous nature of advanced SM (advSM), successive iterations of response criteria have tried to capture different dimensions of the disease, including measures of mast cell burden (percentage of bone marrow mast cells and serum tryptase level), and mast cell-related organ damage (referred to as C findings). Historically, response criteria have been anchored to reversion of one or more organ damage finding(s) as a minimal criterion for response. This is a central principle of the Valent criteria, Mayo criteria, and International Working Group-Myeloproliferative Neoplasms Research and Treatment and European Competence Network on Mastocytosis (IWG-MRT-ECNM) consensus criteria. Irrespective of the response criteria, an ever-present challenge is how to apply response criteria in patients with SM and an associated hematologic neoplasm, where the presence of both diseases complicates assignment of organ damage and adjudication of response. In the context of trials with the selective KIT D816V inhibitor avapritinib, pure pathologic response (PPR) criteria, which rely solely on measures of mast cell burden and exclude consideration of organ damage findings, are being explored as more robust surrogate of overall survival. In addition, the finding that avapritinib can elicit complete molecular responses of KIT D816V allele burden, establishes a new benchmark for advSM and motivates the inclusion of definitions for molecular response in future criteria. Herein, we also outline how the concept of PPR can inform a proposal for new response criteria which use a tiered evaluation of pathologic, molecular, and clinical responses.

Abstract Abstract 2656 Introduction: The International Prognostic Index (IPI) was first developed in 1993 to risk stratify patients with aggressive Non-Hodgkin's lymphoma (NHL) for outcome prediction (Shipp, NEJM, 1993). Since the addition of rituximab to conventional CHOP chemotherapy for the treatment of DLBCL, there have been many efforts to validate the IPI as well as to improve upon the model's capacity to distinguish subgroups with discrete clinical outcomes, especially high-risk patients. Previous studies have focused on adding clinical or biologic prognostic factor(s) to the original model or regrouping the original IPI score (R-IPI; Sehn, Blood, 2007). We, therefore, built anew a modern IPI based solely on clinical factors available in the real world NCCN clinical database. Methods: Using the nationwide population-based NHL lymphoma database from NCCN, patients with newly diagnosed DLBCL enrolled between June 2000 and Dec. 2010 at 7 NCCN cancer centers were included with at least 1 year and up to 5 years of follow-up. Clinical characteristics including age, Ann Arbor stage, ECOG performance status, disease in extranodal sites (including positivity in bone marrow, CNS, liver/GI tract, lung, other sites and spleen), LDH, presence of bulky disease (>10 cm) as well as B symptoms were studied as potential predictors for model development using COX proportional hazards regression. IPI scores were assigned proportionally based on parameter estimates of the statistically significant predictors in the final COX model. Model selection and its comparison to the original IPI model were made based on Akaike Criteria (AIC) and the likelihood ratio test. Categorization of age and LDH was decided by testing the linearity assumption and Martingale residuals. Kaplan-Meier curves were plotted for stratified risk groups per the new and original IPI. Finally, both IPI models were compared using the initial randomly selected 15% validation sample. Results: There were 1,650 DLBCL patients with complete clinical information included for model development. The new IPI model consisted of similar component predictors but used a maximum of 8 scoring points by further categorizing age group into >40–60 (score of 1), >60–75 (score of 2) and >75 yrs (score of 3), and normalized LDH between >1–3 times (score of 1) and 33 times (score of 2) upper limit of normal. These categorizations minimized the Martingale residuals. Age effect was linear and 20-year increments fit the model best, whereas the effect of normalized LDH was not linear and reached plateau at a ratio of 3. Lymphomatous involvement either of bone marrow, CNS, Liver/GI tract or lung appeared as a stronger predictor (p<0.001) than number of extranodal sites (p=0.91). Four risk groups (Low, Low-intermediate, High-intermediate and High) were identified using the current IPI (Table 1) with enhanced discrimination power when compared with the original IPI and better global model fitting statistics, i.e. smaller AIC and significant likelihood ratio test (p<0.001). It was possible to identify a high risk group (score 3 6) with 5-year overall survival of 33% (95% CI: 22%–45%). Better model prediction was also shown in the validation sample. Conclusions: We were able to develop an enhanced IPI model for clinical prediction among previously untreated DLBCL cases by using patient level data from the NCCN NHL database. The NCCN-IPI demonstrates better risk stratification and identifies a poor risk subgroup with <50% 5-year overall survival in the current real-world clinical setting as compared to the original IPI model developed for aggressive lymphoma prior to the rituximab era. Disclosures: No relevant conflicts of interest to declare.

BackgroundPhysipathological mechanisms of spondyloarthritis (SA) are very complex. The role of the interleukin (IL)- 8, which is an angiogenic chemokine, has been suggested [1].ObjectivesWe aimed to evaluate the discriminative value of interleukin 8 in SA.MethodsWe conducted a cross-sectional study during two years (2019-2020) including 144 subjects divided into two groups: a group G1 that included 72 patients followed for spondyloarthritis meeting the Assessement of SpondyloArthritis international Society (ASAS) criteria and a group (G2) including 72 healthy controls. The two groups were matched by age and sex.IL-8 was measured for each participant using chemiluminescence.We performed a ROC analysis and computed the air under the curve (AUC) at IL-8 to assess the ability of this chemokine to diagnose SA and to distinguish between SA patients from healthy controls. Statistical analysis was performed using SPSS.ResultsWe included 57 men and 15 females in each group. The mean age was 44.84 ± 13.42 years. In G1, the mean disease duration was 10.25 ±7.7 years. Axial and peripheral involvements were found in 85% of cases (n=65) and 50% of cases, respectively.The mean BASDAI and ASDAS-CRP were 3.21 ± 1.87 and 2.92 ±1.55, respectively.IL-8 was able to distinguish SA patients from healthy controls with a cutoff of 4.5 pg/mL. The AUC was good at 0.855 (p<0.0001). The sensibility and the specificity were 92.8% and 81.6% (Figure 1).Figure 1.AUC at IL-8 between SA patients and healthy controls 0.855 (p<0.0001)ConclusionSeveral studies have found that IL-8 was significantly higher in SA patients comparing to controls [2,3]. Our study showed that IL-8 could distinguish SA patients from controls with a cutoff of 4.5 pg/mL. This suggests that IL-8 could play a role in the pathophysiology of SA.References[1]König A, Krenn V, Gillitzer R, Glöckner J, Janssen E, Gohlke F, et al. Inflammatory infiltrate and interleukin-8 expression in the synovium of psoriatic arthritis--an immunohistochemical and mRNA analysis. Rheumatol Int. 1997;17(4):159‑68.[2]Limón-Camacho L, Vargas-Rojas MI, Vázquez-Mellado J, Casasola-Vargas J, Moctezuma JF, Burgos-Vargas R, et al. In vivo peripheral blood proinflammatory T cells in patients with ankylosing spondylitis. J Rheumatol. avr 2012;39(4):830‑5.[3]Sonel B, Tutkak H, Düzgün N. Serum levels of IL-1beta, TNF-alpha, IL-8, and acute phase proteins in seronegative spondyloarthropathies. Joint Bone Spine. 1 oct 2002;69(5):463‑7.Disclosure of InterestsNone declared

Abstract Deletion of the long arm of chromosome 5 is the most frequent chromosomal abnormality in MDS (10–15% of MDS cases). Patients with del(5q), particularly those with the ‘5q-syndrome’ have a much better prognosis than other MDS subtypes. Although the presence of additional chromosome abnormalities (ACA), apart from 5q-, has been suggested to negatively influence this favourable outcome, the exact prognostic impact of ACA remains unknown. The aim of the present study was to analyse the prognostic value of ACA in a large series of patients with MDS with 5q- abnormality, treated with supportive care. Three-hundred and five MDS patients with del(5q) were selected from a 3128 cases database that included 1004 patients from the Spanish Haematological Cytogenetics Working Group (GCECGH) (Solé et al., 2005) and 2124 patients from the German-Austrian MDS Study Group (Haase et al., 2007). Patients were separated into two groups: group A (n=204), all del(5q) cases as a single anomaly and group B (n=101) with additional cytogenetic anomalies. Patients in Group B were subdivided according to: the number of additional anomalies (1 to 3 5 anomalies); and the type of additional cytogenetic aberrations: chromosomes 1 and 3, monosomy 7, 7q-, trisomy 8, trisomy 11, trisomy 13, 12p-, involvement of chromosome 17, -18/18q-, 20q-, trisomy 21, loss of X/Y chromosome, and unrelated clones. The series includes 90 males (29.5%) and 215 females (70.5%) with a median age of 66 years (range: 3–92 yr). Using FAB criteria (n=294): 52% had RA, 9% RARS, 30% RAEB, 8% RAEB-t and 1% CMML. WHO classification was available for 217 patients: 52% had ‘5q- syndrome’, 1% RA, 0% RARS, 2% RCMD, 2% RSCMD, 13% RAEB-1, 20% RAEB-2, 1% CMML, 8% AML and 1% were unclassifiable. Overall, 204 (67%) of the patients presented 5q- isolated, 52 (17%) 5q- with one additional abnormality, 10 (3%), 6 (2%), 7 (2%) and 26 (9%) with 2, 3, 4 and 5 or more additional abnormalities, respectively. Follow-up data were available for 273 patients (89.5%). Median survival was 48 months for all. Median survival for patients with isolated del(5q), with one additional abnormality and with two or more additional abnormalities (complex karyotypes) was 69, 55 and 8 months, respectively (P&lt;0.0001). However, no statistical differences were found between patients with isolated del(5q) and patients with only one additional abnormality (P=0.35). Complex karyotypes showed a very adverse outcome. None of the single additional anomalies analysed showed a particular better or worse prognosis. Preliminary results of a multivariate analysis (n=76) showed a highest predictive survival time value for cytogenetics complexity followed by the number of cytopenias and the age. In conclusion, patients with 5q- associated with two or more additional chromosomal abnormalities have a significantly worse overall survival than patients with isolated 5q- or with only one additional anomaly. Our results do not support the exclusion of patients with one single additional chromosomal abnormality and typical bone marrow features from the ‘5q- syndrome’ WHO category. This work is presented on behalf of the Grupo Cooperativo Español de Citogenética Hematológica (GCECGH), German-Austrian MDS Study Group (GASMSG), International Working Group on MDS Cytogenetics of the MDS Foundation.

Abstract Background: Follicular lymphoma (FL) is a heterogenous disease. The optimal timing, sequence and choice of therapy remain matters of debate and there is no optimal prognostic tool. The FLIPI (Follicular Lymphoma International Prognostic Index) is based on five bio-clinical parameters and is widely used, but not as guide for choice of treatment. Recently a new prognostic score (PRIMA-PI), based solely on two parameters, bone marrow involvement and serum beta2 microglobulin (ß2m) was proposed for patients treated with immunochemotherapy (Bachy E., Blood 2018). The Nordic Lymphoma Group (NLG) performed two randomized trials including patients with symptomatic/progressive indolent CD20+ lymphoma, with rituximab monotherapy or rituximab in combination with interferon (IFN)-α2a as primary treatment, without maintenance (Kimby E., 2008, 2015). The 10 years follow-up of these patients showed a good survival with no major safety issues and no need for later chemotherapy in 38% of FL patients (Lockmer S, JCO 2018). Aim/Purpose: To evaluate two different prognostic systems (the new PRIMA-PI and the FLIPI), for overall survival (OS) and time to treatment failure (TTF) in a cohort of symptomatic/progressive FL patients treated with a rituximab-containing first-line regimen without chemotherapy. Methods: Previously untreated patients with a confirmed FL diagnosis (n=269) or indolent lymphoma not otherwise specified (n=22, most FLs with insufficient material for grading), treated in the NLG randomized trials with two cycles rituximab (375 mg/m2 x 4 weeks), with or without IFN-α2a, were classified into the three PRIMA-PI categories: high-risk: ß2m> 3mg / L, intermediate-risk: ß2m ≤ 3 mg / L with bone marrow involvement and low-risk: ß2m ≤ 3 mg / without bone marrow involvement. The FLIPI scores were also assessed. TTF, defined as the interval between randomization and either initiation of new lymphoma therapy due to relapse or intolerance, or death from any cause, as well as OS were estimated using the Kaplan Meier method. The log-rank test was used for comparison between risk groups. Results: Out of 291 patients, 252 had complete data on PRIMA-PI and FLIPI (at the time of randomization in the original trials) and were available for analyses of TTF and OS. Patient characteristics are shown in Table 1. PRIMA-PI seemed to identify a true high-risk group of 47 patients, 32 of them being high risk also according to FLIPI, while a larger patient group (n=117) was classified as FLIPI high-risk. After a long follow-up time, median 9.9 years (0.4 -18.8) from randomization, median 10.6 years for the 214 patients (74%) still alive, 76 patients (26%) were failure-free and 108 (37%) without need of any chemotherapy, Patients with PRIMA-PI high showed a shorter TTF compared to PRIMA-PI intermediate and low (Fig 1a), whereas the FLIPI risk-groups were not significantly separated (Fig 1b). Evidence of transformation to aggressive disease was seen in 55 patients, with no significant difference in frequency between the PRIMA-PI groups, nor between FLIPI groups. Both PRIMA-PI and FLIPI were of significant value for predicting OS, most evident after a long follow-up time (Fig 1c and d). In 41 patients the cause of death was progressive disease or therapy complications, regarded as lymphoma-related death, whereas 21 died of other causes. The lymphoma-specific survival was related to the PRIMA-PI (log-rank p=0.03), but not to the FLIPI (n.s). Prognosis was worse for the PRIMA-PI high-risk group than the for the low-risk, also when adjusted for sex, high age (>60 years), diagnosis, stage, ECOG and FLIPI risk-group; TTF HR 1.82 (95% CI 1.16-2.85, p=0.01) and OS HR 2.3 (95% CI 1.00-5.38, p=0.05). Conclusion: FL patients included in two NLG trials with complete clinical data and a median follow-up of >10 years after randomization have been assessed for validation of different prognostic indices. In these patients, all with chemo-free first-line therapy, the PRIMA-PI was shown a valid predictor of both TTF and OS and seemed more useful than the FLIPI. The PRIMA-PI high risk identified a group of patients (19% of all) with true poor prognosis. Disclosures Kimby: Roche: Honoraria; Roche: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria; AbbVie: Membership on an entity's Board of Directors or advisory committees. Holte:Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees; Roche, Norway: Research Funding. Wahlin:Roche: Research Funding; Gilead: Consultancy, Honoraria, Research Funding. Hagberg:Roche: Honoraria.

Abstract Abstract 649 TRM is among the major challenges for the success of HCT. Over the past two decades advances in the prevention and treatment of the major sources of TRM; regimen related toxicity, graft-versus-host disease (GVHD) and infections, have been made. To estimate the combined effect of these advances over time, we assessed changes in the incidence of TRM from 1985 through 2004 in 5,972 patients younger than 50 years, who received bone marrow (BM) or peripheral blood (PB) HCT with myeloablative conditioning for AML in first (CR1) or second (CR2) complete remission reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). The incidence of TRM was determined for four consecutive five-year periods for HLA-matched sibling donors (MRD) and the later three for unrelated donor (URD) separately by donor type and disease status at transplant. Cox proportional hazard regression models of TRM and overall survival outcomes were constructed with time periods as the main effect. Adjustments for patient and disease characteristics including age, performance score, coexistent diseases and cytogenetics were made in all multivariate models. Subgroup analyses were performed to account for the influence of major changes in transplant characteristics over time, i.e. GVHD prophylaxis, graft source and HLA matching. We observed a steady drop in the risk of TRM over time among patients in CR1 and CR2 receiving MRD transplants, which was associated with a significant reduction in risk of death (table below). Among URD recipients, TRM also improved with lower RR in 2000-2004 compared to earlier periods. No improvements in long term OS was observed in URD CR1 group. For patients in CR2, the RR for overall mortality was 0.74 (0.6-0.9, p=0.03) for 2000-2004 compared to 1990-1994. Subgroup analyses restricted to recipients of BM grafts, cyclosporine/methotrexate for all transplants and partially HLA-matched grafts for URD resulted in similar trends, suggesting that improvements in TRM were not solely related to utilization of PB, newer GVHD prophylaxis or better HLA matching. In conclusion, our results demonstrate lower risk for TRM over time in patients receiving HCT from MRD and URD for AML in CR1 and CR2. These reductions in risk of TRM have been accompanied by reduced risk of overall mortality in most groups of patients studied. Disclosures: No relevant conflicts of interest to declare.

Abstract An HLA-matched sibling has been considered the optimal donor for allogeneic hematopoietic cell transplantation (HSCT). However, several potential transplant recipients may have a haploidentical sibling or an offspring who may also serve as donors. In this study, we sought to determine the optimal alternative related donor (haploidentical sibling or an offspring) as compared to an HLA-matched sibling. The primary objective was comparison of chronic graft-versus-host disease (GVHD). Secondary outcomes included acute GVHD, non-relapse mortality (NRM), relapse, treatment failure (relapse or death, inverse of relapse-free survival) and overall mortality. The study population included 4540 donor-recipient pairs (n=218 haploidentical sibling; n=218 offspring; n=4104 HLA-matched sibling) with acute myeloid (n=3617) and acute lymphoblastic (n=923) leukemia transplanted in 2008 to 2015. There were few offspring (n=87) who donated to patients aged 18-54 years and haploidentical siblings (n=61) who donated to patients aged 55-76 years and were excluded from the analysis. Post-transplant cyclophosphamide (PT-Cy) with calcineurin inhibitor (CNI) and mycophenolate was used for GVHD prophylaxis for all haploidentical HSCTs. HLA-matched siblings received CNI-containing GVHD prophylaxis; CNI with methotrexate was the predominant prophylaxis regimen. Patient age was correlated with donor age and donor-recipient relationship. Bone marrow was the predominant graft for haploidentical HSCTs (64%) and peripheral blood (89%) for HLA-matched sibling HSCTs. Younger patients (age 18-54 years) of were more likely to receive reduced intensity conditioning regimens for haploidentical HSCTs compared to HLA-matched sibling HSCTs (22%). Among older patients, conditioning regimen intensity did not differ by donor type. Exploratory analysis confirmed differences in survival by patient age. Therefore, based on differences in survival by patient age, two age groups were created: 18 - 54 years and 55 - 76 years and within each patient age group, donor-recipient relationship and its effect on transplant outcomes were tested using Cox regression models. In addition to the standard Cox regression model, we also performed a matched-pair analysis. Recipients of haploidentical HSCT (cases; n=436) were matched to HLA-matched siblings (controls; n=1707) on age, disease and disease risk index. 88% of patients aged 18-54 years were matched to 4 controls and 96% of patients aged 55-76 years were matched to 4 controls. The median difference in age between cases and controls were 0.08 (range 0-9.9) years for patients aged 18-54 years and 0.05 (0 - 9.5) years for patients aged 55-76 years. The results of multivariate Cox regression and matched-pair analysis are shown in Tables 1, 2. Among patients aged 18-54 years, chronic GVHD risks were lower after haploidentical sibling compared to HLA-matched sibling HSCT. There were no differences in acute GVHD, NRM, relapse, treatment failure or overall mortality. Among patients aged 55-76 years, acute and chronic GVHD risks were lower after offspring compared to HLA-matched sibling HSCT. But risks for NRM, treatment failure and overall mortality were higher after offspring compared to HLA-matched sibling HSCT. The 2-year probabilities of overall survival, adjusted for disease risk index and sex are shown in Figure 1. In summary, chronic GVHD rates were lower after haploidentical HSCT with PT-Cy containing GVHD prophylaxis regimens compared to HLA-matched sibling HSCT for all patients. Whether this can be attributed solely to the GVHD prophylaxis regimen or in part attributed to use of peripheral blood grafts for HLA-matched sibling HSCT must be studied further in a setting in which PT-Cy containing GVHD prophylaxis is used for HLA-matched sibling HSCT. Despite lower chronic GVHD with haploidentical sibling donor HSCT with PT-Cy, NRM and overall survival did not differ by donor type for patients aged 18-54 years. However, for patients aged 55 - 76 years, despite lower chronic GVHD with offspring donor HSCT with PT-Cy, NRM was higher and overall survival was lower compared to HLA-matched sibling HSCT. Definitive proof of these findings would require a prospective randomized trial. Disclosures Ciceri: GSK: Other: B-thalassemia gene therapy was developed by Fondazione Telethon and Ospedale San Raffaele and has been inlicenced by GSK that provides funding for the clinical trial, Research Funding. Mohty: Sanofi: Honoraria, Speakers Bureau.

Abstract Introduction: Second-Harmonic Generation microscopy (SHG) has provided progresses in extracellular matrix research, mainly regarding automated analysis of collagen fibers. Nodular sclerosis-classical Hodgkin lymphoma (NS) often has a rich collagen deposition, which remains poorly explored in its biological significance and potential prognostic role. The aim of this study was to characterize the collagen component of NS using SHG, and to investigate its clinical value. Methods: Hematoxylin and eosin stained slides from 53 consecutive samples of paraffin embedded NS tissue were analyzed by SHG imaging in an Inverted Zeiss LSM 780-NLO. HIV-positive individuals were excluded. For comparative purposes, 11 reactive lymph nodes (RL) were also randomly selected. In each slide, 3 capsular areas and 3 sclerotic regions (perinodular septa - PS - in NS and fibrotic foci around germinal centers in RL) were chosen. Collagen near blood vessels was not considered. We evaluated quantity, uniformity and organization of the fibers with ImageJ and OrientationJ plug-in in 4 hotspots from each image. Shapiro-Wilk test was used to assess data normality, while t-tests and Pearson correlations were performed to analyze collagen parameters between two groups. Overall survival (OS) was defined as time from diagnosis until death from the disease or last follow-up. Event-free survival (EFS) was set as time from diagnosis until progressive disease, death from the disease or last follow-up. Collagen data were used in survival analyses as continuous variables (in Cox-hazards model) or categorical ones (by choosing the mean value as a threshold for Kaplan-Meier curves and log-rank test). Significance was set at p<0.05. Results: NS patients were mostly female (58.5%). The mean and median values of age at diagnosis were, respectively, 33 and 29 years (range: 14-82 years). Forty-two patients (79.2%) had B-symptoms, while bulky disease was seen in 23 cases (43.3%). Bone marrow was infiltrated in 4 patients (7.5%). Based on the International Prognostic Score (IPS), patients were stratified as follows: 39 (73.5%) as low-risk (IPS ≤ 3) and 14 (26.5%) as high-risk (IPS > 3). The first-line treatment was ABVD in 40 cases (75.5%) and BEACOPP in 13 patients (24.5%). Radiotherapy was performed in 27 (50.9%) patients. Tumor PS presented more dense (p<0.01), organized (p<0.01) and uniform (p=0.02) fibers than sclerosis in RL. NS capsule had only a more organized collagen than RL (p=0.02). Considering solely NS, we found significant correlations of collagen fibers quantity (r=0.67), uniformity (r=0.78) and organization (r=0.49) between capsule and PS, suggesting a proportional deposition of collagen in these compartments. When clinical data were analyzed in the entire patient group, the presence of more organized PS collagen was associated with low-risk IPS (p=0.03), grade 2 tumors (p= 0.04), extranodal disease (p=0.003) and a higher risk of death (p=0.02). On the other hand, a higher fiber organization in NS capsule was only associated with low-risk IPS (p=0.03). The presence of high-risk IPS was associated with a shorter EFS (p=0.002), but had no relationship to OS. Collagen parameters had no impact on EFS. However, in univariate Cox regression, higher collagen quantity (p=0.04) in PS was the only factor associated with a worse OS. When only high-risk IPS cases were analyzed in Cox regression model, PS collagen had association with unfavorable OS regarding higher collagen quantity (p=0.03) and uniformity (p<0.01). In this setting, a higher quantity of capsular collagen was also associated with a worse OS (p=0.02). We did not perform multivariate analysis in this group due to the small amount of patients (14). Also in the high-risk cases, using the mean value of PS collagen quantity (15.19) as a threshold to binarize data, we found a trend to worse OS in cases with a higher collagen quantity (p=0.05, figure 1). Considering only low-risk IPS cases, collagen factors had no association with OS. Conclusion: Collagen parameters in NS have distinct features than in RL and affect clinical presentation of the tumor. Moreover, collagen quantity and uniformity in cases with high-risk IPS were associated with survival, which indicates that incorporation of collagen information might be relevant in the prognostication of NS. Figure 1. Survival curve of high-risk patients (n=14) stratified according to the perinodular collagen (pCOL) quantity threshold. Figure 1. Survival curve of high-risk patients (n=14) stratified according to the perinodular collagen (pCOL) quantity threshold. Disclosures No relevant conflicts of interest to declare.

Abstract Background: Hypereosinophilia (HE) often requires extensive workup and in some instances quickly enough to identify the cause, considering the nature of the end organ damage which is likely to occur if a proper treatment is not initiated on time. This includes primarily a search for various secondary causes. In their absence,an evaluation of a clonal process is required which is complicated by the absence of any definite morphological or immunophenotypic features differentiating clonal from non-clonal conditions. PDGFRA, PDGFRB and FGFR1 related clonal HE and lymphocytic variant of reactive HE are two distinct groups of hypereosinophilic disorders requiring specific management. There are several reports of these disorders in the recent past from different parts of the world. However, there is no comprehensive data about the prevalence or etiology of these disorders from a tropical country like India. While WHO 2008 classification is solely intended for classifying neoplastic hypereosinophilia, the system proposed by International Cooperative Working Group on Eosinophil Disorders (ICOG-EO) in 2011 appears to be more comprehensive covering familial, reactive, neoplastic, idiopathic and other HE related single and multisystem disorders. Methods and materials: A prospective study was conducted from January 2014 to May 2015 and a retrospective analysis of cases diagnosed between January 2009 and December 2013 was performed using hospital records. A comprehensive clinico-pathological evaluation was performed in all prospective cases by extensive work up including flow cytometry for T cell abnormalities and FISH for PDGFRA, PDGFRB and FGFR1 abnormalities. An attempt was made to classify HE [>1.5 x 109/L eosinophils in peripheral blood or >20% of all nucleated cells in the bone marrow (BM)] and hypereosinophilic syndromes (HES; HE with organ damage) according to the ICOG-EO classification. Results: A diagnosis of HE was made in a total of 101 patients (2.6 cases per month) over a period of 77 months (1-72 years, male to female ratio 1.8:1). 71 patients had either a sufficient follow up or work-up required for final categorization. 26.7% of patients were children. A diagnosis of HES was made in 21 patients (29.6%). The reactive HE was the commonest cause (73.9% of HE or 47.9% of all patients) followed by clonal or neoplastic HE (21.7% of HE or 14.1% of all patients). Similar to HE, HES was most commonly secondary in nature (61.9% of HES or 18.3% of all patients), followed by Idiopathic HES (19% of HES or 5.6% of all) and neoplastic HES (14.2% of HES and 4.2% of all). Helminthic infections especially filariasis, toxocariasis and trichinellosis; and giardiasis were important causes of HE. The identification of exact etiological agent required testing for a wide spectrum of pathological agents. T-NHL was the most important cause of reactive HE secondary to neoplasms. HE preceded the diagnosis of ALL, AML, Hodgkin lymphoma and cutaneous T cell lymphoma in one patient each. In three patients (4.2% all patients or 14.3% of HES) L-HES was diagnosed based on immunophenotype abnormalities (CD3-CD4+ in one patients and CD4+CD8+ T cells in two patients), response to steroids and requirement of long-term steroid for control of HE. BCR-ABL1 and JAK2V617F positivity was detected in 4.2% and 1.4% patients. There were no patients with rearrangement of PDGFRA, PDGFRB or FGFR1 genes. However HE was responsive to imatinib (BCR-ABL1 negative) in three (4.2%) retrospectively recruited patients (PDGFRA, PDGFRB or FGFR1 not tested). A comparison of HE associated malignancies with HE associated with benign disorders showed that maximum TLC (p=0.03), presence of blasts in the peripheral blood (p=0.008), higher BM blast% (p=0.01), lower platelet counts (0.02) were associated with malignancy. Higher percentage of eosinophils in both peripheral blood (p=0.0004) and BM (p=0.04) was associated with benign disorders. Absolute eosinophil count did not differentiate malignancy from benign conditions. IgE levels were generally higher in patients with benign disorders. Conclusions: Our study shows that HE is frequent in India and is most commonly secondary to infections. HE can precede, succeed or can occur concurrently with various malignancies and autoimmune diseases. There were no confirmed cases of PDGFRA, PDGFRB and FGFR1 associated HE. The exact prevalence of these cases needs to be examined in a larger cohort. Disclosures No relevant conflicts of interest to declare.

Background: Novel agent induction and AHCT remains the preferred initial therapeutic strategy for transplant-eligible MM patients. Current prognostic tools in MM focus solely on disease-specific factors at diagnosis to determine patient prognosis-International Staging System (ISS) and revised-ISS (R-ISS). A major limitation to both, the ISS and R-ISS, is that they are not specific for HCT-eligible patients and do not take into account other patient factors that may enter into a decision to pursue AHCT. The data used to generate these staging systems were from broad populations with varying upfront treatment strategies and included patients who were ineligible for intensive therapy. Additionally, there is considerable interest in identifying the population that relapses early despite modern induction/AHCT approaches who are candidates for novel approaches for maintenance/consolidation. To address these problems, we used data from the Center for Blood and Marrow Transplant Research (CIBMTR) registry to identify disease-, patient-, and transplantation-specific variables that are associated with progression-free survival (PFS) in patients undergoing upfront AHCT (within 12 months of diagnosis). Methods: We used the outcomes of 2528 MM patients undergoing upfront AHCT from 2008-2017 reported to the CIBMTR. Patients were divided into training and validation sets with a 50% random split. High risk cytogenetics was defined as the presence of one or more of the following: t(4;14), t (14;16), t (14;20), del 13q, del 17p, 1q gain, or 1p deletion. We used a Cox multivariable model to identify factors prognostic of progression free survival (PFS) in a training subset. The regression coefficients of the final model was transformed into a risk score with an appropriate transformation. A weighted score using these factors was assigned to the training cohort (n = 917) and validation cohort (n=897) using subset that had all values that entered the final model. Kaplan-Meier estimates of the individual scores were used to classify patients into risk groups for both cohorts. Results: Baseline characteristics of these patients are shown in Table 1. No cytogenetic abnormality, VRD induction, pre-AHCT bone marrow plasma cells (BMPCs) &lt;10% and 1 line of induction chemotherapy were assigned 0 points. Pre-AHCT BMPCs ≥10% (hazard ratio HR, 1.47; 95% CI, 1.19-1.83), use of ≥2 lines of induction chemotherapy prior to AHCT (HR 1.32; 95% CI 1.06-1.64), standard cytogenetic risk vs. no abnormality (HR 1.41; 95% CI 1.13-1.77) and induction regimens (non-VRD regimens vs. VRD) (HR 1.4, 95% CI 1.17-1.74) were associated with increased hazard of progression and assigned 1 point in the scoring system. Presence of high-risk cytogenetics vs. no abnormality (HR 1.87; 95% CI 1.45-2.42) was assigned 2 points, and the use of thalidomide and dexamethasone (TD) as an induction regimen (HR 2.19; 95% CI 1.48-3.2) was assigned 3 points. A two-category system was created based on the scoring: low risk (0-3) and high risk (4-6). The scoring system was prognostic for PFS when applied to both cohorts. High-risk group was found to have significantly higher risk of progression and/or death compared to low risk in training (HR 2.2; 95% CI 1.74-2.86; p&lt;0.0001) and validation cohort (HR 1.7, 95% CI 1.30-2.22; p=0.0001) respectively (Table 2). The 3-year PFS in the training cohort was 60% (95% CI 56%-64%) in low risk and 27% (95% CI 17%- 36%) in high risk while in the validation cohort was 51% (95% CI 47%-55%) in low risk and 28% (95% CI 16%- 39%) in high risk (Figure 1A and 1B). Conclusions: We describe a prognostic model specifically for patients undergoing upfront AHCT in MM which can identify patients at very high risk for early relapse/progression. These patients should be ideal candidates for studies of immunotherapy or other interventions after AHCT aimed at reducing relapse. Disclosures Dhakal: Sanofi: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees. Kumar:Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Research Funding. Shah:Genentech, Seattle Genetics, Oncopeptides, Karoypharm, Surface Oncology, Precision biosciences GSK, Nektar, Amgen, Indapta Therapeutics, Sanofi: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Nkarta: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees; Teneobio: Consultancy, Membership on an entity's Board of Directors or advisory committees; University of California, San Francisco: Employment; Poseida: Research Funding; Indapta Therapeutics: Equity Ownership; Celgene, Janssen, Bluebird Bio, Sutro Biopharma: Research Funding. Qazilbash:Amgen: Consultancy, Other: Advisory Board; Autolus: Consultancy; Bioclinical: Consultancy; Genzyme: Other: Speaker. D'Souza:EDO-Mundapharma, Merck, Prothena, Sanofi, TeneoBio: Research Funding; Prothena: Consultancy; Pfizer, Imbrium, Akcea: Membership on an entity's Board of Directors or advisory committees. Hari:AbbVie: Consultancy, Honoraria; Cell Vault: Equity Ownership; Sanofi: Honoraria, Research Funding; Spectrum: Consultancy, Research Funding; Amgen: Research Funding; Kite: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; BMS: Consultancy, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding.

Abstract Background: Axi-cel is a US FDA-approved autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy for treatment of adult patients (pts) with relapsed or refractory large B cell lymphoma after ≥ 2 prior lines of therapy. In ZUMA-1, the pivotal study of pts with refractory large B cell lymphoma, the objective response rate (ORR) was 82%, including a 58% complete response (CR) rate (Neepalu and Locke, et al. N Engl J Med. 2017). Grade ≥ 3 cytokine release syndrome (CRS) and neurologic events were observed in 12% and 31% of pts, respectively, and were generally reversible. Checkpoint proteins, such as PD-1 and PD-L1, have been shown to be expressed on both CAR T cells and in the tumor microenvironment and subsequently upregulated after CAR T cell infusion (Vranic, et al. PLoS One. 2017; Cherkassky, et al. J Clin Invest. 2016; Galon, et al. ASCO 2017. #3025). This suggests that axi-cel activity could be augmented by incorporating PD-L1 blockade. This end of Phase 1 analysis of ZUMA-6 examines the safety and preliminary efficacy of axi-cel in combination with the anti-PD-L1 antibody atezolizumab (atezo) in pts with refractory diffuse large B cell lymphoma (DLBCL; NCT02926833). Methods: Eligible pts (≥ 18 years) with refractory DLBCL, defined as stable or progressive disease to last line of therapy or relapse within 12 months after autologous stem cell transplant, must have recieved prior CD20-targeting and anthracycline-containing regimen and had ECOG ≤ 1 and adequate bone marrow and organ function. Pts received low-dose conditioning with fludarabine 30 mg/m2/day and cyclophosphamide 500 mg/m2/day × 3 days followed by axi-cel infusion at a target dose of 2 × 106 cells/kg. Atezo was administered at 1200 mg every 21 days for 4 doses starting on Day 21, 14, and 1 post-axi-cel infusion for Cohorts 1, 2, and 3, respectively. This report describes Phase 1 results from all 3 cohorts. Incidence of dose-limiting toxicities (DLTs) was the primary endpoint. Secondary endpoints included the frequency of adverse events (AEs), disease response, pharmacokinetics, and biomarkers. Results: As of January 19, 2018, 12 pts have received axi-cel and at least 1 dose of atezo (3 in Cohort 1; 3 in Cohort 2, 6 in Cohort 3). Median age was 55 years (range, 30 - 66). Most pts (9/12, 75%) had received ≥ 3 prior therapies, and 4 pts (33%) had an International Prognostic Index score of 3 or 4. The median follow-up from axi-cel infusion was 4.4 months (range, 0.8 - 12.6), with 50% of pts having ≥ 6 months of follow-up. Eight pts (67%) have received all 4 doses of atezo, and 11/12 pts have received all scheduled doses of atezo. One pt in Cohort 3 experienced a DLT of Grade 4 thrombocytopenia and neutropenia lasting longer than 30 days. All pts experienced at least 1 AE (92% Grade ≥ 3), with no apparent exacerbation or recurrence of axi-cel-related toxicity following atezo infusion. Only 1 Grade ≥ 3 AE was attributed solely to atezo. Overall, the most common grade ≥ 3 AEs were anemia (9/12, 75%), encephalopathy (5/12, 42%), and neutropenia (5/12, 42%). Grade ≥ 3 CRS and neurologic events occurred in 3 (25%) and 6 (50%) pts, respectively. The ORR in evaluable pts was 9/10 (90%), with 6 pts (60%) in CR and 3 (30%) in partial response (PR); 2/6 pts (33%) had converted to CR at month 6 and month 9 after initially achieving a PR. CAR T cell expansion as measured by area under the curve in the first 28 days (AUC0-28) was over 2-fold higher in ZUMA-6 than the median observed in pts with DLBCL in ZUMA-1 (ZUMA-6: median, 823 cells/µL × days, range, 99 - 2301; ZUMA-1: median, 357 cells/µL × days, range, 5 - 11,507; Figure). Median CAR T cell levels remained higher than ZUMA-1 beyond 28 days. However, initial peak CAR T cell levels were similar (ZUMA-6: median, 68 cells/µL, range, 9 - 274; ZUMA-1: median, 32 cells/µL, range, 1 - 1513). Interferon-γ (IFNγ) levels peaked within the first week after axi-cel infusion and reached a median of 730.5 pg/mL (range, 212 - 1876). The median peak IFNγ level in pts from ZUMA-6 was 1.5-fold higher than that from pts enrolled in Cohort 1 of ZUMA-1 (493.8 pg/mL, range, 32.4 - 1876). Conclusions: PD-L1 blockade with atezo following axi-cel infusion has a manageable safety profile, with a low incidence of DLTs and no clinically significant evidence of increased incidence of AEs. Encouraging efficacy results support the opening of Phase 2 of ZUMA-6 in which 22 pts will be treated according to the Cohort 3 schedule. Pharmacokinetic data suggest the potential for enhanced CAR T cell expansion. Figure. Figure. Disclosures Locke: Kite Pharma: Other: Scientific Advisor; Novartis Pharmaceuticals: Other: Scientific Advisor; Cellular BioMedicine Group Inc.: Consultancy. Miklos:Kite - Gilead: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy, Research Funding; Pharmacyclics - Abbot: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Genentech: Research Funding; Janssen: Consultancy, Research Funding. Herrera:Merck, Inc.: Consultancy, Research Funding; Immune Design: Research Funding; Pharmacyclics: Consultancy, Research Funding; KiTE Pharma: Consultancy, Research Funding; Seattle Genetics: Research Funding; Gilead Sciences: Research Funding; AstraZeneca: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Genentech: Consultancy, Research Funding. Westin:Apotex: Membership on an entity's Board of Directors or advisory committees; Celgen: Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Membership on an entity's Board of Directors or advisory committees. Lee:Kite Pharma, Caladrius Biosciences: Employment; Kite Pharma, Caladrius Biosciences: Equity Ownership; Kite Pharma: Other: TRAVEL, ACCOMMODATIONS, EXPENSES. Rossi:KITE: Employment. Zheng:Kite Pharma: Employment. Avanzi:Kite Pharma: Employment. Roberts:KITE: Employment. Sun:Kite, a Gilead Company: Employment.

»My name is Boye, I dig carins and old mounds«The archaeologist Vilhelm Christian BoyeThe story of Vilhelm Boye is the history of one man’s passionate and insightful involvement in archaeology, which from the first was directed solely towards the Bronze Age. His involvement led to an academic disaster in his youth, but left behind it a developed skill in field archaeology. Despite his problems he persisted with what most obsessed him, namely the preservation of Denmark’s oak coffin graves. His multi-facetted personality and his more popular approach to archaeology may have challenged his contemporaries, and certainly contributed to his more or less deliberate exclusion from a permanent appointment at the Museum of Northern Antiquities in Copenhagen. Even though he was opposed by powerful people within the Copenhagen museum establishment for nearly twenty years, he had the natural facility of easily winning the trust of others. This enabled him to cope with the situation and turn it to his advantage wherever he found himself. His marriage to Mimi Drachmann brought a welcome stability to his life, but his lack of professional recognition and his exclusion from a place at the top of archaeology continued. Time was running out for Boye, but he managed to leave an impressive body of published work behind him.Vilhelm Christian Boye was the son of the Norwegian-born priest and writer of hymns Caspar Johannes Boye. In 1848 his father was moved to the garrison church in Copenhagen, where the family lived at 29 Bredgade until his father’s death from cholera in 1853. This was a fashionable part of town, its residents including both the composer Niels W. Gade and Professor Adam Oehlenschläger, and even more notably J.J.A. Worsaae lived in the same property as the Boye family from 1850 to 1852. It was probably through his neighbour Worsaae that Boye later became a member of the circle around C.J. Thomsen. We may therefore assume that Boye visited and spent many after-school hours at the Museum of Northern Antiquities, and soon became an assistant during the public tours.Early in the 1840s tension arose between Worsaae and Thomsen, because Thomsen did not want to make Worsaae a junior museum inspector. Worsaae had not hitherto received any stipend or official position, and with some justice felt himself hard done by. Thomsen however did not respond to his request, so he left the Museum, later to be made Director for the Preservation of Ancient monuments. At the same time he taught at Copenhagen University, where Boye from time to time came to his lectures. There is no doubt that Boye wanted an academic career, and presumably hoped that his involvement with the Museum of Northern Antiquities would allow him to complete a study of Scandinavian archaeology. In the meantime Boye studied at the Museum under the direction of both Thomsen and Herbst.In early October 1857 Boye undertook one of his first excavations of a Bronze Age mound, the so-called Loholm barrow at Snørumnedre Mark (fig. 1). The dating of the grave however caused problems for him, but through a comparative study of Bronze Age burial rituals he concluded that the grave had close parallels within this period.The following year three funerary urns and some bronze objects were found in Hullehøj barrow, near Kjeldbymagle on the island of Møn. The barrow was going to be blown up, but the local judge had the work stopped and sent Boye to lead the excavation in May 1859. As the excavation progressed, Boye was able to ascertain that there were both cremations and inhumations in one and the same barrow. The inhumations were surrounded by fist-sized stones and placed at the bottom of the barrow, the cremations higher up within the mound. In comparison with his earlier barrow excavations it is worth noting Boye’s stratigraphic observations, which for the first time supported the division of the Bronze Age into an earlier and a later section. This hypothesis had been suggested earlier, but not hitherto adequately demonstrated. In 1859 Boye published the results of his excavations of 1857-8, as well as those of his recently completed excavation of Aasehøj barrow at Raklev, in the periodical Annaler for Nordisk Oldkyndighed og Historie for 1858. This article is his first independent scientific publication, and should have attracted greater attention than it in fact did. In modern perspective the article is a perfectly competent archaeological publication, in which Boye solely through field observations reaches the conclusion that the Bronze Age could be divided into two periods, each with its own burial ritual. Even though Boye had been close to understanding why both cremations and inhumations occurred in the same barrow as early as 1857, he did not reach his final understanding this early. In November 1857 Worsaae had in fact given lectures at the university in which he suggested a division of the Bronze Age, but it is noteworthy that he had not earlier published any or all of his conclusions. His work on the subdivision of the Stone Age was probably more important to Worsaae, while the subdivision of the Bronze Age was more of a footnote, a natural outgrowth of the idea that there was continuous development from one stage to the next. Boye’s article in Annaler thus inevitably supported Worsaae’s hypothesis, although this was presumably not the intention. On the contrary, Boye merely intended to publish his own conclusions. Boye cannot therefore be said to be the sole originator of the subdivision of the Bronze Age, but apart his barrow investigations there was nobody else who reached the same conclusion at the time independently of Worsaae.In 1860 Boye took part in the first major bog excavations, at Vimose and then at Thorsbjerg with Engelhardt. Despite adverse circumstances and appalling weather, the Thorsbjerg excavations produced several important finds including Roman coins, a gilt breastplate, and also a very unusual face mask of silver with gilt (fig. 2). Although Engelhardt did not publish the full excavation report until 1863-69, Boye presented his observations in Annaler as early as 1860, where he discussed earlier interpretations of the many weapons found in bogs. Boye observed that the universal destruction of these weapons did not happen by chance, but was deliberate. Furthermore, the weapons lay in groups of one type, and the shields were pierced by spear points to pin them to the bottom of the bog. Boye’s interpretation of the finds was thus remarkably accurate, because he regarded them as votive offerings of the spoils of war.When Prussian and Austrian troops crossed the Ejder River on 1st February 1864, Boye volunteered within the month and was promoted to lance corporal (fig. 3). In May he was landed to take part in the defence of the island of Als along with the other Danish forces. On his return home in August Boye continued his work at the Museum of Northern Antiquities, but Thomsen’s health was failing, and after a long illness he died on 21st May 1865. The question of who was to succeed Thomsen had long been discussed, and it was indeed Worsaae who was appointed. Although Herbst had been groomed for the job by Thomsen, he found himself outmanouevred. Boye probably already knew by then that he would not be given a position at the Museum. Herbst, his confidant, could no longer help him, and Thomsen’s awareness of his archaeological skills was of no use either. Circumstances thus forced Boye to leave the Museum.Boye’s relationship with the family friend and poet H.C. Andersen resulted in the latter recommending Boye in December 1867 as a Danish tutor to the Brandt family in Amsterdam (fig. 4). On Wednesday 22nd January 1868 Boye departed for Amsterdam via Kiel. During his stay Boye wrote regularly to Andersen, who also travelled to Amsterdam to visit him. His stay in Amsterdam was evidently good for Boye, and contributed to the fact that he never lost his love for archaeology. As early as late August of the same year, Boye travelled to southern Halland in Sweden at the request of Ritmester Peter von Möller, to examine and excavate a large group of barrows known as the Ätterhögar on the Drömmestrup estate, the excavation of which was concluded in early July 1869. Boye thus returned home just in time to take part as a member of the Danish Committee in the International Congress of Archaeology and Anthropology that was held in Copenhagen from 25th August to 5th September. But his love of Schleswig and the old borderland called him, and soon Boye moved permanently to Haderslev to work as a freelance writer on the daily paper Dannevirke under the editorship of H.R. Hiort-Lorenzen.His coverage of the International Congress of Archaeology and Anthropology meeting in Copenhagen is the most extensive of Boye’s writings in Dannevirke. He also wrote a series of articles with a marked archaeological-ethnographic content, for example on the antiquities of Brazil, and the discovery of ­Australia.Although Boye supported himself as a writer for Dannevirke, his main occupation seems rather to have been the investigation of the burial mounds of Schleswig, which before 1864 had only been intermittently examined by amateurs. Boye began an extensive programme, and without his efforts and initiative, knowledge of many Schleswig barrows would have been lost. Although the information he recorded was not particularly satisfactory, in that it was mostly based on the memory of local people, his efforts should be seen as a precursor, because the work of protection went slowly at the time. In his search for lost information, in 1875 Boye considered the barrow at Dybvadgård north of Åbenrå, which had been partially excavated by Prince Carl of Prussia in 1864. During the excavations the Prince’s soldiers found an oak coffin, which was despatched to the Museum für Völkerkunde in Berlin. Boye therefore wrote direct to the Prince, who in reply sent a photograph and description of the coffin. During the next eight years Boye managed to accumulate a great deal of information about the barrows of Schleswig, but his work was not without risk, because several of his “missions” involved evading the Prussian authorities and their power to confiscate the antiquities which Boye from time to time illegally sent to the Museum in Copenhagen.In 1874 the Principal of Herlufsholm School, C. Hall, engaged Vilhelm Boye to organise the school’s collection of antiquities, which had been in store for nearly twenty years. In addition to this reorganisation, funds were also made available for the systematic excavation of a nearby barrow at Grimstrup (fig. 5). The barrow however contained very little, mainly urns full of cremated bone, but the excavation was thoroughly recorded and a series of drawings was produced by R. Bertelsen, the school’s teacher of drawing. After this Boye set to work to display the collection in the six cases that were made available. The greater part of the collection came from the Stone Age, filling no fewer than five cases, giving an impression both of coastal finds from shell middens, and grave finds. The Bronze Age display contained only a few bronzes, but rather more pots. Iron Age artifacts were hardly represented at all, and consisted mostly of whetstones, a bowl-shaped buckle, and a pot burnt black.In November of the same year Boye was working at Herlufsholm, he produced his remarkable work Vejledning til Udgravning af Oldsager og deres foreløbige Behandling [Guide to the Excavation of Antiquities and their Initial Study], published under the auspices of the Society for the Historical-Antiquarian Collection in Århus. Boye’s Guide is the first of its type, and one can clearly detect his close association with Herbst, who had contributed to the scientific content of the work.Boye’s link with the antiquarian collection in Århus had not come about by chance. During his time at the Museum of Northern Antiquities he had early on made contact with the person mainly responsible for the establishment of the Århus collection, Edvard Erslev. Boye joined the museum in 1871, re-arranged the collection, and produced a guide for visitors. For the first time the museum acquired a new and professional look. Boye thus functioned as part of the leadership until 1876, when he gave up his museum post in favour of the schoolteacher Emmerik Høegh-Guldberg. The continued problems facing Dannevirke and Hiort-Lorenzen’s mounting confrontation with the judicial authorities in Flensborg probably caused Boye to consider his position with the newspaper. This culminated with the expulsion of Hiort-Lorenzen, who then took up the post of chief editor of Nationaltidende in Copenhagen. Boye also travelled to Copenhagen in early 1878, and on 15th November the year after he married Mimi Drachmann, sister of the poet Holger Drachmann (fig. 6 ). Not suprisingly, Boye got a job at the Nationaltidende, where he edited the newspaper’s Archaeological and Ethnographic Communications until 1885. In the seven years Boye worked at the paper, no fewer than 150 numbers of the Communications appeared, Boye writing more than 400 pages of them himself. The articles include a multiplicity of archaeological and ethnographic topics such as “Egypt’s Ancient Cultures” and “A Copper Age in Scandinavia”.In 1882 Count Emil Frijs of Frijsenborg commissioned Boye to catalogue and organise his estate’s collection of prehistoric and medieval objects, which came from the area round the lake and castle ruin at Søborg in northern Zealand. Attempts had been made to drain the lake since 1793, and several antiquities had been found at various times during the work. The recording project culminated in the publication of a small book, Fund af Gjenstande fra Oldtiden og Middelalderen i og ved Søborg Sø [Finds of Objects from the Prehistoric and Medieval Periods in and around Søborg Lake], which among other things contains some of the first photographic illustrations of Danish antiquities (fig. 7).Worsaae’s death in 1885 inaugurated a new era, and Herbst was finally able to take over the post of head of the Museum (fig. 8). Boye’s long friendship with Herbst had in the previous years resulted in him becoming a regional inspector for the Museum. Herbst was probably even then considering Boye for a future post in the Museum, and was indicating that he himself could not be overlooked when it became time to nominate a successor to Worsaae. After his appointment to the Museum of Northern Antiquities in 1885, Boye continued his activities as inspector in northern Zealand, and was frequently called when new finds were recovered from Bronze Age barrows.In contrast to Herbst, Boye rapidly fell in with the group of younger workers, particularly Henry Petersen (fig. 9). Over the years they became close friends with a common interest in new finds, as during the excavation of Guldhøj in 1891. Boye had no draftsman at the excavation, but he did have a local photographer who recorded some aspects of the opening of the first oak coffin. These are the first photographs ever to be taken during an excavation, even though photography by then was nothing new (fig. 10).With the reorganising of the National Museum, Boye was made senior assistant of the historical section on 1st April 1892, under Henry Petersen. He was responsible for the Museum’s archive and library, but fieldwork and travels are what particularly characterise his work in these years. When the small Bronze Age barrow on which the Glavendrup rune stone had been erected in 1864 was nearly completely destroyed by ploughing, Boye undertook a restoration of the barrow itself and the associated ship-shaped arrangement of stones in 1892 (fig. 11). The restoration’s outcome was the construction of a new barrow on which was placed the rune stone, and the re-erection of the stones in the ship arrangement.At the same time, chamberlain A. Oxholm undertook a small excavation of the Bronze Age barrow at Tårnholm, and recovered an oak coffin containing the remains of a woman, a fine necklace, a belt plate, and a small bronze dagger. Boye was immediately informed, and in connection with his investigations at Tårnborg was able to go to Tårnholm and lead a new excavation of the barrow, in which A.P. Madsen was also involved, and recover two more oak coffins (fig. 12).If we now consider Boye’s last major work, the publication of the major volume Fund af Egekister fra Bronzealderen i Danmark [Finds of Oak Coffins from the Danish Bronze Age], there are several indications that suggest that Boye began the work with the early intention that its coverage should be wide, and contain his long-term investigations into and knowledge of the country’s oak coffin graves. It is particularly noteworthy that his work as an archaeological journalist and with the Archaeological and Ethnographic Communications seems to have been a kind of precursor to this, as the last chapters contain sections that are clearly derived from his contributions to the Communications. The manuscript was completed in April 1896, and A.P. Madsen prepared for it no fewer than 27 full-page folio sized copperplates. The work was dedicated to “the veterans of Danish archaeology”, C.F. Herbst the museum director, and Japetus Steenstrup, with whom Boye had first collaborated more recently.His many years of a wandering existence and work-related disruptions had however told on him, and soon after the book was published Boye became ill. From his private correspondence from 1896 it emerges that Boye often had insufficient time to be with his nearest and dearest. Despite his illness he travelled one last time to visit relatives at Viken, but his illness worsened and he had to travel rapidly to Lund and on to Copenhagen. Boye died on 22nd September apparently as the result of a stroke, and was buried in Søllerød churchyard north of Copenhagen.Boye’s potential as a researcher was noticed early on by Thomsen, but just as quickly suppressed by Worsaae, who may more or less deliberately have sought to out-manoeuvre his colleague. Boye’s character and energy may have seemed a threat, and although he never finished an academic education he nevertheless displayed a remarkable archaeological acuity, but was unable to bolster his own reputation. Some of the blame for this must rest with the Museum’s aged leaders, who never supported or developed Boye’s evident skills to any great extent. It must also be stressed that some of Boye’s earlier career problems are closely connected to the lack of vision and jealousy of these same leaders. When he departed for Amsterdam Boye had no expectation of a Museum post, but despite this he intelligently kept up his contacts with Copenhagen, particularly with Herbst, knowing full well that Worsaae’s leadership would one day end. This somewhat bold presumption turned out to be correct, and helped his archaeological career.There is no doubt that Boye in his later years tried hard to recover his lost reputation and save his career from the disaster it suffered when he was younger, but the price was high and it also affected his health. We must today recognise that his reputation was restored to the highest level, and we must thank him for the fact that, through him, a uniquely detailed knowledge of the Bronze Age people themselves was preserved for Danish archaeology, as well as of their most prominent contribution to the Danish landscape: the barrows.Anders Otte StensagerInstitut for forhistorisk arkæologiKøbenhavns UniversitetTranslated by Peter Rowley-Conwy

AbstractThe hometown of Jesus, Nazareth, is an international center of Christian pilgrimage that has capitalized on showcasing its sacred sites. Architect Antonio Barluzzi was commissioned to design Nazareth’s modern Basilica of the Annunciation in 1954, and a cornerstone for the project was laid in a well-attended ceremony. It seems that the establishment of the modern church was the catalyst for the eagerness with which the Israeli authorities approached establishing a Jewish monument in the region. In 1957, a design process for the Central Synagogue in Nazareth Illit (subsequently renamed Nof HaGalil) began, with the aim of proudly competing with the churches and mosques in the Nazareth region. Both the basilica and the synagogue were erected by Israeli construction firm Solel Boneh and were inaugurated in 1968 and 1969, respectively. This article examines the impact of the inception, establishment and building of Nazareth’s Basilica of the Annunciation on the drive to strengthen Jewish presence in the Nazareth region, which in turn stood behind the construction of the Nazareth Illit synagogue. This research is based on a comparative investigation of the histories of both structures, including early design proposals, architecture, and the religious artworks therein. This comparative investigation reveals the influence of the basilica on the synagogue and the shared aspects of their design and execution. While existing literature dedicated to the Central Synagogue in Nazareth Illit has focused on its significance and meaning as an Israeli architectural landmark, this article presents a new perspective, examining how a modern architectural trend was used as an agent in the struggle between local Jewish and Christian monumental dominance. It also contributes to the literature by shedding light on a heretofore overlooked quest for an appropriate architectural style for religious buildings in the Land of Israel during the mid-twentieth century.

In a TEXT essay in 2004, Philip Edmonds wrote about the publication prospects of graduates of creative writing programs. He depicted the publishing industry of the 1970s and 1980s as a field driven by small presses and literary journals, and lamented the dearth of these publications in today’s industry. Edmonds wrote that our creative writing programs as they stand today are under-performing as they do not deliver on the prime goal of most students: publication. “Ultimately,” he wrote, “creative writing programs can only operate to their full potential alongside an expanding and vibrant publishing culture” (1). As a creative writing and publishing lecturer myself, and one who teaches in the field of publishing and editing, this anxiety rings quite true. I am inherently interested in the creation of a strong and vibrant publishing industry so that promising students and graduates might get the most out of their degrees. As the popularity of creative writing programs grows, what relationships are being formed between writing programs and the broader publishing industry? Furthermore, does a role and responsibility exist for universities themselves to foster the publication of the emerging writers they train? Edmonds argued that the answer could be found not in universities, but in state writers’ centres. He advocated a policy whereby universities and the Australia Council funded the production of literary magazines through state writers’ centres, resulting in a healthier publishing marketplace for creative writing graduates (6). This paper offers a second alternative to this plan, arguing that university presses can play a role in the development of a healthier Australian publishing industry. To do so, it cites three examples of university press interactions with both the broad writing and publishing industry, and more specifically, with creative writing programs. The paper uses these examples—University of Queensland Press, University of Western Australia Press, and Giramondo Publishing (UWS)—in order to begin a broader conversation regarding the role universities can play in the writing and publishing industry. Let us begin by thinking about the university and its traditional role in the development of literature. The university can be thought of as a multi-functional literary institution. This is not a new concept: for centuries, there has been an integral link between the book trade and the university, with universities housing “stationers, scribes, parchment makers, paper makers, bookbinders, and all those associated with making books” (Clement 317). In universities today, we see similar performances of the various stages of literary production. We have students practising creative writing in both undergraduate and postgraduate coursework programs. We have the editing of texts and mentoring of writers through postgraduate creative writing supervision. We have the distribution of texts through sales from university bookshops, and the mass storage and loans of texts in university libraries. And we have the publication of texts through university presses.This point of literary production, the publication of texts through university presses, has traditionally been preoccupied with the publication of scholarly work. However, a number of movements within the publishing industry towards the end of the twentieth century resulted in some university presses shifting their objectives to incorporate trade publishing. The globalization of the publishing industry in the early 1990s led to a general change in the decision-making process of mainstream publishers, where increasingly, publishers looked at the commercial viability of texts rather than their cultural value. These movements, defined by the takeover of many publishing houses by media conglomerates, also placed significant financial pressure on smaller publishers, who struggled to compete with houses now backed by significantly increased fiscal strength. While it is difficult to make general statements about university presses due to their very particular nature, one can read a trend towards trade publishing by a number of university presses in an attempt to alleviate some of these financial pressures. This shift can be seen as one interaction between the university and the broader creative writing discipline. However, not all university presses waited until the financial pressures of the 1990s to move to trade publishing. For some presses, their trade lists have played a significant role in defining their relationship with literary culture. One such example in the Australian landscape is University of Queensland Press. UQP was founded in 1948, and subsisted as purely a scholarly publisher until the 1960s. Its first movements into trade publishing were largely through poetry, originally publishing traditional hardback volumes before moving into paperback, a format considered both innovative and risky at the time. David Malouf found an early home at UQP, and has talked a number of times about his relationship with the press. His desire to produce a poetry format which appealed to a new type of audience spawned the press’s interest in trade publishing. He felt that slim paperback volumes would give poetry a new mass market appeal. On a visit to Brisbane in 1969 I went to talk to Frank Thompson (general manager) at the University of Queensland Press… I told him that I did have a book but that I also had a firm idea of the kind of publication I wanted: a paperback of 64 pages that would sell for a dollar. Frank astonished me by saying … that if his people told him it was financially viable he would do it. He picked up the phone, called in his production crew … and after a quarter of an hour of argument and calculations they came up with the unit cost of, I think, twenty-three cents. ‘Okay, mate,’ Frank told me, ‘you’re on.’ I left with a firm undertaking and a deadline for delivery of the manuscript. (Malouf 72-73) That book of poetry, Bicycle and Other Poems, was Malouf’s first solo volume. It appeared in bookstores in 1970 alongside other slim volumes by Rodney Hall and Michael Dransfield, two men who would go on to become iconic Brisbane poets. Together, these three bold experiments in paperback poetry publishing sold a remarkable 7,000 copies and generated these sales without school or university adoptions, and without any Commonwealth Literary Fund assistance, either. UQP went on to publish 159 new titles of poetry between 1968 and 1996, becoming a significant player in the Australian literary landscape. Through University of Queensland Press’s poetry publishing, we see a way of how the university can interact with the broader writing and publishing industry. This level of cohesion between the publishing house and the industry became one of the distinguishing features of the press in this time. UQP garnered a reputation for fostering Australian writing talent, launching the careers of a generation of Australian authors. Elizabeth Jolley, Roger McDonald, Beverley Farmer, Thea Astley, Janette Turner Hospital, and Peter Carey all found their first home at the press. The university’s publishing house was at the forefront of Australian literary development at a time when Australia was beginning to blossom, culturally, as a nation. What this experience shows is the cultural importance and potential cultural benefit of a high level of cohesion between the university press and the broader writing and publishing industry. UQP has also sought to continue a high level of social cohesion with the local community. The press is significant in that it inhabits a physical space, the city of Brisbane, which is devoid of any other significant trade publishers. In this sense, UQP, and by association, the University of Queensland, has played a leading role in the cultural and literary development of the city. UQP continues to sponsor events such as the Brisbane Writers Festival, and publishes the winning manuscript for the Emerging Queensland Author award at the annual Queensland Premier’s Literary Awards. Another point of interest in this relationship between the press and the university at University of Queensland can be seen in the relationship between UQP and some of the staff in the university’s creative writing department. Novelist, Dr Venero Armanno, senior lecturer in the creative writing program at UQ, shifted from a major international publisher back to his employer’s publishing house in 2007. Armanno’s move to the press was coupled with the appointment at UQP of another University of Queensland creative writing senior lecturer, Dr Bronwyn Lea, as poetry editor (Lea has recently left this post). This sort of connection shapes the public face of creative writing within the university, and heightens the level of cohesion between creative writing programs and university publishing. The main product of this interaction is, perhaps, the level of cohesion between university press and creative writing faculty that the relationship outwardly projects. This interaction leads us to question whether more formal arrangements for the cohesion between creative writing departments and university presses can be put in place. Specifically, the two activities beg the question: why can’t university publishers who publish trade fiction make a commitment to publish work that comes out of their own creative writing programs, and particularly, work out of their research higher degrees? The short answer to this seems to be caught up in the differing objectives of university presses and creative writing programs. The matter is not as cut-and-dry as a press wanting to publish good manuscripts, and a creative writing program, through its research by creative practice, providing that work. A number of issues get in the way: quality of manuscripts, editorial direction of press, areas of specialisation of creative writing faculty, flow of numbers through creative writing programs, to name a few. University of Western Australia Publishing recently played with the idea of how these two elements of creative writing within the university, manuscript production and trade publishing, could work together. UWA Publishing was established in 1935 as UWA Press (the house changed its name to UWA Publishing in 2009). Like University of Queensland Press, the house provides an important literary and cultural voice in Perth, which is not a publishing hub on the scale of Sydney or Melbourne. In 2005, the press, which had a tradition as a strong scholarly publisher and emerging trade publisher, announced a plan to publish a new series of literary fiction written by students in Australian creative writing courses. This was a new idea for UWA Publishing, as the house had previously only published scholarly work, along with natural history, history and children’s books.UWA Publishing fiction series editor Terri-Ann White said that the idea behind the series was to use creative writing postgraduate degrees as a “filter” to get the best emerging writing in Australia.There’s got to be something going for a student writer working with an experienced supervisor with all of the resources of a university. There’s got to be an edge to that kind of enterprise. (In Macnamara 3) As this experiment began in 2005, the result of the press’s doctrine is still unclear. However, it could be interesting to explore the motivations behind the decision to focus fiction publishing on postgraduate student work. Many presses publish student work—N.A. Bourke’s The Bone Flute and Julienne van Loon’s Road Story come to mind as two examples of successful work produced in a creative writing program—but few houses advertise where the manuscript has come from. This is perhaps because of the negative stigma that goes along with student work, that the writing is underdeveloped or, perhaps, formulaic, somehow over-influenced by its supervisor or home institution. UWA Publishing’s decision to take fiction solely from the pool of postgraduate writers is a bold one, and can be seen perhaps as noble by those working within the walls of the university. Without making any assumptions about the sales success of the program, the decision does shape the way in which the press is seen in the broader writing and publishing industry. We can summise from the decision that the list will have a strong literary focus, that the work will be substantial and well-researched, to the point where it could contribute to the bulk of a Masters degree by research, or PhD. The program would also appear to appeal to writing students within the university, all of whom go through their various degrees being told how difficult publication can be for first time writers. Another approach to the relationship between university presses and the broader writing and publishing industry can be seen at the University of Western Sydney. UWS founded a group in 2005 called the Writing and Society Research Group. The group manages the literary journal Heat Magazine and the Giramondo book imprint. Giramondo Publishing was established in 1995 with “the aim of publishing quality creative and interpretative writing by Australian authors”. It states its objectives as seeking to “build a common ground between the academy and the marketplace; to stimulate exchange between Australian writers and readers and their counterparts overseas; and to encourage innovative and adventurous work that might not otherwise find publication because of its subtle commercial appeal” ("Giramondo History"). These objectives demonstrate an almost utopian idea of engaging with the broader writing and publishing industry—here we have a university publisher actively seeking to publish inventive and original work, the sort of work which might be overlooked by other publishers. This philosophical approach indicates the gap which university presses (in an ideal world) would fill in the publishing industry. With the financial support of the university (and, in the case of Giramondo and others, funding bodies such as the Australia Council), university presses can be in a unique position to uphold more traditional literary values. They can focus on the cultural value of books, rather than their commercial potential. In this way, the Writing and Society Research Group at UWS demonstrates a more structural approach to the university’s engagement with the publishing industry. It engages with the industry as a stakeholder of literary values, fulfilling one of the roles of the university as a multi-functional literary institution. It also seeks directly to foster the work of new and emerging writers. Not all universities and university presses will have the autonomy or capacity to act in such a way. What is necessary is constant thought, debate and action towards working out how the university press can be a dynamic and relevant industry player. References Clement, Richard. “Cataloguing Medieval and Renaissance Manuscripts.” The Library Quarterly 55 (1985): 316-326. Edmonds, Philip. “Respectable or Risqué: Creative Writing Programs in the Marketplace.” TEXT 8.1 (2004). 27 Jan. 2010 < http://www.textjournal.com.au/april04/edmonds.htm >. “Giramondo History.” Giramondo Publishing. 27 Jan. 2010 < http://www.giramondopublishing.com/history >. Greco, Albert N., Clara E. Rodriguez, and Robert M. Wharton. The Culture and Commerce of Publishing in the 21st Century. Stanford: Stanford Business Books, 2007. Macnamara, Lisa. “Big Break for Student Writers.” The Australian 2 Nov. 2005: Features 3. Malouf, David. In Munro, Craig, ed. UQP: The Writer’s Press: 1948 – 1998. St Lucia: University of Queensland Press, 1998.

Follicular lymphoma (FL) is the most common type of indolent lymphoma in the Western world, accounting for approximately 30% of lymphoma cases. FL is known for its recurrent nature, necessitating diverse treatment options. The introduction of rituximab, an anti-CD20 antibody, has greatly improved FL outcomes and paved the way for targeted therapies. In this review, we thoroughly explore the structure, mechanism of action, clinical outcomes, and side effects of currently approved monoclonal antibodies (mAb) for FL. Furthermore, we provide insights into ongoing clinical trials and emerging monoclonal antibodies that hold promise for the future of FL treatment. A comprehensive literature search was conducted using various medical databases, including ASH and ASCO publications, as well as PubMed. The clinicaltrials.gov website was used to compile a list of investigational monoclonal antibodies from ongoing clinical trials. The future of antibody-based therapy for follicular lymphoma shows great promise, with a focus on enhancing antibody efficacy, prioritizing optimized combination therapies to address treatment resistance, and evaluating bispecific antibodies as first-line therapies, all while carefully balancing risks and benefits and sequencing treatments appropriately for better disease management. These directions have the potential to establish antibodies as a central component of follicular lymphoma treatment. Article Details How to Cite MOUSTAFA, Muhamad Alhaj. A Comprehensive Review of Monoclonal Antibodies for the Treatment of Follicular Lymphoma Including Both Approved and Investigational Options. Medical Research Archives, [S.l.], v. 11, n. 11, nov. 2023. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/4745>. Date accessed: 02 dec. 2023. doi: https://doi.org/10.18103/mra.v11i11.4745. ABNT APA BibTeX CBE EndNote - EndNote format (Macintosh & Windows) MLA ProCite - RIS format (Macintosh & Windows) RefWorks Reference Manager - RIS format (Windows only) Turabian Issue Vol 11 No 11 (2023): November Issue, Vol.11, Issue 11 Section Research Articles The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives. References 1. Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375-2390. doi:10.1182/blood-2016-01-643569 2. Cerhan JR. Epidemiology of Follicular Lymphoma. Hematol Oncol Clin North Am. 2020;34(4):631-646. doi:10.1016/j.hoc.2020.02.001 3. Kaseb H, Ali MA, Koshy NV. Follicular Lymphoma. In: StatPearls. StatPearls Publishing; 2023. Accessed April 8, 2023. http://www.ncbi.nlm.nih.gov/books/NBK538206/ 4. Monga N, Nastoupil L, Garside J, et al. Burden of illness of follicular lymphoma and marginal zone lymphoma. Ann Hematol. 2019;98(1):175-183. doi:10.1007/s00277-018-3501-8 5. Mozas P, Sorigué M, López-Guillermo A. Follicular lymphoma: an update on diagnosis, prognosis, and management. Med Clin (Barc). 2021;157(9):440-448. doi:10.1016/j.medcli.2021.03.041 6. Luminari S, Bellei M, Biasoli I, Federico M. Follicular lymphoma - treatment and prognostic factors. Rev Bras Hematol E Hemoter. 2012;34(1):54-59. doi:10.5581/1516-8484.20120015 7. Illidge T, Chan C. How have outcomes for patients with follicular lymphoma changed with the addition of monoclonal antibodies? Leuk Lymphoma. 2008;49(7):1263-1273. doi:10.1080/10428190802090805 8. Steffanoni S, Ghielmini M, Moccia A. Chemotherapy and treatment algorithms for follicular lymphoma: a look at all options. Expert Rev Anticancer Ther. 2015;15(11):1337-1349. doi:10.1586/14737140.2015.1092386 9. Flowers CR, Leonard JP, Nastoupil LJ. Novel immunotherapy approaches to follicular lymphoma. Hematol Am Soc Hematol Educ Program. 2018;2018(1):194-199. doi:10.1182/asheducation-2018.1.194 10. Marofi F, Rahman HS, Achmad MH, et al. A Deep Insight Into CAR-T Cell Therapy in Non-Hodgkin Lymphoma: Application, Opportunities, and Future Directions. Front Immunol. 2021;12:681984. doi:10.3389/fimmu.2021.681984 11. Bhatt VR, Armitage JO. Autologous and allogeneic hematopoietic stem cell transplantation in follicular lymphoma. Expert Opin Biol Ther. 2016;16(1):57-66. doi:10.1517/14712598.2016.1096341 12. Lin Z, Liu L, Li Z, Xu B. Bispecific antibodies as monotherapy or in combinations for non-hodgkin B-cell lymphoma: latest updates from the American society of hematology 2022 annual meeting. Exp Hematol Oncol. 2023;12(1):41. doi:10.1186/s40164-023-00404-3 13. Coiffier B, Thieblemont C, Van Den Neste E, et al. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d’Etudes des Lymphomes de l’Adulte. Blood. 2010;116(12):2040-2045. doi:10.1182/blood-2010-03-276246 14. van Meerten T, Hagenbeek A. Novel antibodies against follicular non-Hodgkin’s lymphoma. Best Pract Res Clin Haematol. 2011;24(2):231-256. doi:10.1016/j.beha.2011.03.002 15. Marcus R, Davies A, Ando K, et al. Obinutuzumab for the First-Line Treatment of Follicular Lymphoma. N Engl J Med. 2017;377(14):1331-1344. doi:10.1056/NEJMoa1614598 16. Johnston PB, Bondly C, Micallef INM. Ibritumomab tiuxetan for non-Hodgkin’s lymphoma. Expert Rev Anticancer Ther. 2006;6(6):861-869. doi:10.1586/14737140.6.6.861 17. Gondran C, Ysebaert L. [Drug approval: Mosunetuzumab - third-line therapy in follicular lymphoma]. Bull Cancer (Paris). 2022;109(11):1105-1106. doi:10.1016/j.bulcan.2022.07.010 18. Allen HC, Sharma P. Histology, Plasma Cells. In: StatPearls. StatPearls Publishing; 2023. Accessed April 11, 2023. http://www.ncbi.nlm.nih.gov/books/NBK556082/ 19. Nelson PN, Reynolds GM, Waldron EE, Ward E, Giannopoulos K, Murray PG. Monoclonal antibodies. Mol Pathol MP. 2000;53(3):111-117. doi:10.1136/mp.53.3.111 20. Köhler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975;256(5517):495-497. doi:10.1038/256495a0 21. Dunn DL. Monoclonal antibodies for diagnosis and treatment. Arch Surg Chic Ill 1960. 1993;128(11):1274-1280. doi:10.1001/archsurg.1993.01420230102016 22. Posner J, Barrington P, Brier T, Datta-Mannan A. Monoclonal Antibodies: Past, Present and Future. Handb Exp Pharmacol. 2019;260:81-141. doi:10.1007/164_2019_323 23. Di Pauli F, Berger T, Reindl M. Monoclonal antibodies in the treatment of multiple sclerosis. Curr Med Chem. 2009;16(36):4858-4868. doi:10.2174/092986709789909585 24. Lloyd EC, Gandhi TN, Petty LA. Monoclonal Antibodies for COVID-19. JAMA. 2021;325(10):1015. doi:10.1001/jama.2021.1225 25. Kaur N, Goyal A, Sindhu RK. Therapeutic Monoclonal Antibodies in Clinical Practice against Cancer. Anticancer Agents Med Chem. 2020;20(16):1895-1907. doi:10.2174/1871520620666200703191653 26. Yamada T. Therapeutic monoclonal antibodies. Keio J Med. 2011;60(2):37-46. doi:10.2302/kjm.60.37 27. Reff ME, Carner K, Chambers KS, et al. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood. 1994;83(2):435-445. 28. Cerny T, Borisch B, Introna M, Johnson P, Rose AL. Mechanism of action of rituximab: Anticancer Drugs. 2002;13:S3-S10. doi:10.1097/00001813-200211002-00002 29. Alas S, Bonavida B. Rituximab inactivates signal transducer and activation of transcription 3 (STAT3) activity in B-non-Hodgkin’s lymphoma through inhibition of the interleukin 10 autocrine/paracrine loop and results in down-regulation of Bcl-2 and sensitization to cytotoxic drugs. Cancer Res. 2001;61(13):5137-5144. 30. Golay J, Zaffaroni L, Vaccari T, et al. Biologic response of B lymphoma cells to anti-CD20 monoclonal antibody rituximab in vitro: CD55 and CD59 regulate complement-mediated cell lysis. Blood. 2000;95(12):3900-3908. 31. Jacobsen E. Follicular lymphoma: 2023 update on diagnosis and management. Am J Hematol. 2022;97(12):1638-1651. doi:10.1002/ajh.26737 32. Herold M, Haas A, Srock S, et al. Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group Hematology and Oncology Study. J Clin Oncol Off J Am Soc Clin Oncol. 2007;25(15):1986-1992. doi:10.1200/JCO.2006.06.4618 33. Hiddemann W, Kneba M, Dreyling M, et al. Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2005;106(12):3725-3732. doi:10.1182/blood-2005-01-0016 34. Marcus R, Imrie K, Belch A, et al. CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood. 2005;105(4):1417-1423. doi:10.1182/blood-2004-08-3175 35. Marcus R, Imrie K, Solal-Celigny P, et al. Phase III study of R-CVP compared with cyclophosphamide, vincristine, and prednisone alone in patients with previously untreated advanced follicular lymphoma. J Clin Oncol Off J Am Soc Clin Oncol. 2008;26(28):4579-4586. doi:10.1200/JCO.2007.13.5376 36. Salles G, Mounier N, de Guibert S, et al. Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: results of the GELA-GOELAMS FL2000 study. Blood. 2008;112(13):4824-4831. doi:10.1182/blood-2008-04-153189 37. Colombat P, Salles G, Brousse N, et al. Rituximab (anti-CD20 monoclonal antibody) as single first-line therapy for patients with follicular lymphoma with a low tumor burden: clinical and molecular evaluation. Blood. 2001;97(1):101-106. doi:10.1182/blood.v97.1.101 38. Ghielmini M, Schmitz SFH, Cogliatti SB, et al. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood. 2004;103(12):4416-4423. doi:10.1182/blood-2003-10-3411 39. Witzig TE, Vukov AM, Habermann TM, et al. Rituximab therapy for patients with newly diagnosed, advanced-stage, follicular grade I non-Hodgkin’s lymphoma: a phase II trial in the North Central Cancer Treatment Group. J Clin Oncol Off J Am Soc Clin Oncol. 2005;23(6):1103-1108. doi:10.1200/JCO.2005.12.052 40. Salles G, Seymour JF, Offner F, et al. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet Lond Engl. 2011;377(9759):42-51. doi:10.1016/S0140-6736(10)62175-7 41. Martinelli G, Schmitz SFH, Utiger U, et al. Long-term follow-up of patients with follicular lymphoma receiving single-agent rituximab at two different schedules in trial SAKK 35/98. J Clin Oncol Off J Am Soc Clin Oncol. 2010;28(29):4480-4484. doi:10.1200/JCO.2010.28.4786 42. Hanif N, Anwer F. Rituximab. In: StatPearls. StatPearls Publishing; 2023. Accessed April 15, 2023. http://www.ncbi.nlm.nih.gov/books/NBK564374/ 43. Freeman CL, Sehn LH. A tale of two antibodies: obinutuzumab versus rituximab. Br J Haematol. 2018;182(1):29-45. doi:10.1111/bjh.15232 44. Goede V, Klein C, Stilgenbauer S. Obinutuzumab (GA101) for the treatment of chronic lymphocytic leukemia and other B-cell non-hodgkin’s lymphomas: a glycoengineered type II CD20 antibody. Oncol Res Treat. 2015;38(4):185-192. doi:10.1159/000381524 45. Mössner E, Brünker P, Moser S, et al. Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity. Blood. 2010;115(22):4393-4402. doi:10.1182/blood-2009-06-225979 46. Niederfellner G, Lammens A, Mundigl O, et al. Epitope characterization and crystal structure of GA101 provide insights into the molecular basis for type I/II distinction of CD20 antibodies. Blood. 2011;118(2):358-367. doi:10.1182/blood-2010-09-305847 47. Suresh T, Lee LX, Joshi J, Barta SK. New antibody approaches to lymphoma therapy. J Hematol OncolJ Hematol Oncol. 2014;7:58. doi:10.1186/s13045-014-0058-4 48. Radford J, Davies A, Cartron G, et al. Obinutuzumab (GA101) plus CHOP or FC in relapsed/refractory follicular lymphoma: results of the GAUDI study (BO21000). Blood. 2013;122(7):1137-1143. doi:10.1182/blood-2013-01-481341 49. Amitai I, Gafter-Gvili A, Shargian-Alon L, Raanani P, Gurion R. Obinutuzumab-related adverse events: A systematic review and meta-analysis. Hematol Oncol. 2021;39(2):215-221. doi:10.1002/hon.2828 50. Riley MB. Ibritumomab tiuxetan. Clin J Oncol Nurs. 2003;7(1):110-112. doi:10.1188/03.CJON.109-112 51. Morschhauser F, Radford J, Van Hoof A, et al. 90Yttrium-ibritumomab tiuxetan consolidation of first remission in advanced-stage follicular non-Hodgkin lymphoma: updated results after a median follow-up of 7.3 years from the International, Randomized, Phase III First-LineIndolent trial. J Clin Oncol Off J Am Soc Clin Oncol. 2013;31(16):1977-1983. doi:10.1200/JCO.2012.45.6400 52. Witzig TE, Flinn IW, Gordon LI, et al. Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab-refractory follicular non-Hodgkin’s lymphoma. J Clin Oncol Off J Am Soc Clin Oncol. 2002;20(15):3262-3269. doi:10.1200/JCO.2002.11.017 53. Rieger K, De Filippi R, Lindén O, et al. 90-yttrium-ibritumomab tiuxetan as first-line treatment for follicular lymphoma: updated efficacy and safety results at an extended median follow-up of 9.6 years. Ann Hematol. 2022;101(4):781-788. doi:10.1007/s00277-022-04781-3 54. Alhaj Moustafa M, Borah BJ, Moriarty JP, et al. Yttrium-90 Ibritumomab Tiuxetan is Cost-Effective Compared to Bendamustine + Rituximab in Low-grade Lymphomas. Clin Lymphoma Myeloma Leuk. 2023;23(4):259-265. doi:10.1016/j.clml.2023.01.010 55. Salvaris R, Ong J, Gregory GP. Bispecific Antibodies: A Review of Development, Clinical Efficacy and Toxicity in B-Cell Lymphomas. J Pers Med. 2021;11(5):355. doi:10.3390/jpm11050355 56. Budde LE, Sehn LH, Matasar M, et al. Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. Lancet Oncol. 2022;23(8):1055-1065. doi:10.1016/S1470-2045(22)00335-7 57. Jacobson CA, Chavez JC, Sehgal AR, et al. Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase 2 trial. Lancet Oncol. 2022;23(1):91-103. doi:10.1016/S1470-2045(21)00591-X 58. Shimabukuro-Vornhagen A, Gödel P, Subklewe M, et al. Cytokine release syndrome. J Immunother Cancer. 2018;6(1):56. doi:10.1186/s40425-018-0343-9 59. Grigor EJM, Fergusson D, Kekre N, et al. Risks and Benefits of Chimeric Antigen Receptor T-Cell (CAR-T) Therapy in Cancer: A Systematic Review and Meta-Analysis. Transfus Med Rev. 2019;33(2):98-110. doi:10.1016/j.tmrv.2019.01.005 60. Nitschke L. The role of CD22 and other inhibitory co-receptors in B-cell activation. Curr Opin Immunol. 2005;17(3):290-297. doi:10.1016/j.coi.2005.03.005 61. Tang T, Cheng X, Truong B, Sun L, Yang X, Wang H. Molecular basis and therapeutic implications of CD40/CD40L immune checkpoint. Pharmacol Ther. 2021;219:107709. doi:10.1016/j.pharmthera.2020.107709 62. Dakappagari N, Ho SN, Gascoyne RD, Ranuio J, Weng AP, Tangri S. CD80 (B7.1) is expressed on both malignant B cells and nonmalignant stromal cells in non-Hodgkin lymphoma. Cytometry B Clin Cytom. 2012;82(2):112-119. doi:10.1002/cyto.b.20631 63. Deeks ED. Polatuzumab Vedotin: First Global Approval. Drugs. 2019;79(13):1467-1475. doi:10.1007/s40265-019-01175-0 64. Han Y, Liu D, Li L. PD-1/PD-L1 pathway: current researches in cancer. Am J Cancer Res. 2020;10(3):727-742. 65. Rosenbaum CA, Jung SH, Pitcher B, et al. Phase 2 multicentre study of single-agent ofatumumab in previously untreated follicular lymphoma: CALGB 50901 (Alliance). Br J Haematol. 2019;185(1):53-64. doi:10.1111/bjh.15768 66. Hagenbeek A, Gadeberg O, Johnson P, et al. First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma: results of a phase 1/2 trial. Blood. 2008;111(12):5486-5495. doi:10.1182/blood-2007-10-117671 67. Czuczman MS, Fayad L, Delwail V, et al. Ofatumumab monotherapy in rituximab-refractory follicular lymphoma: results from a multicenter study. Blood. 2012;119(16):3698-3704. doi:10.1182/blood-2011-09-378323 68. Morschhauser F, Leonard JP, Fayad L, et al. Humanized anti-CD20 antibody, veltuzumab, in refractory/recurrent non-Hodgkin’s lymphoma: phase I/II results. J Clin Oncol Off J Am Soc Clin Oncol. 2009;27(20):3346-3353. doi:10.1200/JCO.2008.19.9117 69. Morschhauser F, Marlton P, Vitolo U, et al. Results of a phase I/II study of ocrelizumab, a fully humanized anti-CD20 mAb, in patients with relapsed/refractory follicular lymphoma. Ann Oncol Off J Eur Soc Med Oncol. 2010;21(9):1870-1876. doi:10.1093/annonc/mdq027 70. Tobinai K, Ogura M, Kobayashi Y, et al. Phase I study of LY2469298, an Fc-engineered humanized anti-CD20 antibody, in patients with relapsed or refractory follicular lymphoma. Cancer Sci. 2011;102(2):432-438. doi:10.1111/j.1349-7006.2010.01809.x 71. Ganjoo KN, de Vos S, Pohlman BL, et al. Phase 1/2 study of ocaratuzumab, an Fc-engineered humanized anti-CD20 monoclonal antibody, in low-affinity FcγRIIIa patients with previously treated follicular lymphoma. Leuk Lymphoma. 2015;56(1):42-48. doi:10.3109/10428194.2014.911859 72. Leonard JP, Coleman M, Ketas JC, et al. Phase I/II trial of epratuzumab (humanized anti-CD22 antibody) in indolent non-Hodgkin’s lymphoma. J Clin Oncol Off J Am Soc Clin Oncol. 2003;21(16):3051-3059. doi:10.1200/JCO.2003.01.082 73. Advani A, Coiffier B, Czuczman MS, et al. Safety, pharmacokinetics, and preliminary clinical activity of inotuzumab ozogamicin, a novel immunoconjugate for the treatment of B-cell non-Hodgkin’s lymphoma: results of a phase I study. J Clin Oncol Off J Am Soc Clin Oncol. 2010;28(12):2085-2093. doi:10.1200/JCO.2009.25.1900 74. Ogura M, Tobinai K, Hatake K, et al. Phase I study of inotuzumab ozogamicin (CMC-544) in Japanese patients with follicular lymphoma pretreated with rituximab-based therapy. Cancer Sci. 2010;101(8):1840-1845. doi:10.1111/j.1349-7006.2010.01601.x 75. Kebriaei P, Cutler C, de Lima M, et al. Management of important adverse events associated with inotuzumab ozogamicin: expert panel review. Bone Marrow Transplant. 2018;53(4):449-456. doi:10.1038/s41409-017-0019-y 76. Hamadani M, Radford J, Carlo-Stella C, et al. Final results of a phase 1 study of loncastuximab tesirine in relapsed/refractory B-cell non-Hodgkin lymphoma. Blood. 2021;137(19):2634-2645. doi:10.1182/blood.2020007512 77. Salles G, Gopal AK, Minnema MC, et al. Phase 2 Study of Daratumumab in Relapsed/Refractory Mantle-Cell Lymphoma, Diffuse Large B-Cell Lymphoma, and Follicular Lymphoma. Clin Lymphoma Myeloma Leuk. 2019;19(5):275-284. doi:10.1016/j.clml.2018.12.013 78. Fanale M, Assouline S, Kuruvilla J, et al. Phase IA/II, multicentre, open-label study of the CD40 antagonistic monoclonal antibody lucatumumab in adult patients with advanced non-Hodgkin or Hodgkin lymphoma. Br J Haematol. 2014;164(2):258-265. doi:10.1111/bjh.12630 79. Czuczman MS, Thall A, Witzig TE, et al. Phase I/II study of galiximab, an anti-CD80 antibody, for relapsed or refractory follicular lymphoma. J Clin Oncol Off J Am Soc Clin Oncol. 2005;23(19):4390-4398. doi:10.1200/JCO.2005.09.018 80. Armand P, Janssens A, Gritti G, et al. Efficacy and safety results from CheckMate 140, a phase 2 study of nivolumab for relapsed/refractory follicular lymphoma. Blood. 2021;137(5):637-645. doi:10.1182/blood.2019004753 81. Press OW, Unger JM, Braziel RM, et al. Phase II trial of CHOP chemotherapy followed by tositumomab/iodine I-131 tositumomab for previously untreated follicular non-Hodgkin’s lymphoma: five-year follow-up of Southwest Oncology Group Protocol S9911. J Clin Oncol Off J Am Soc Clin Oncol. 2006;24(25):4143-4149. doi:10.1200/JCO.2006.05.8198 82. Leonard JP, Coleman M, Kostakoglu L, et al. Abbreviated chemotherapy with fludarabine followed by tositumomab and iodine I 131 tositumomab for untreated follicular lymphoma. J Clin Oncol Off J Am Soc Clin Oncol. 2005;23(24):5696-5704. doi:10.1200/JCO.2005.14.803 83. Press OW, Unger JM, Rimsza LM, et al. Phase III randomized intergroup trial of CHOP plus rituximab compared with CHOP chemotherapy plus (131)iodine-tositumomab for previously untreated follicular non-Hodgkin lymphoma: SWOG S0016. J Clin Oncol Off J Am Soc Clin Oncol. 2013;31(3):314-320. doi:10.1200/JCO.2012.42.4101 84. Nastoupil LJ, Chin CK, Westin JR, et al. Safety and activity of pembrolizumab in combination with rituximab in relapsed or refractory follicular lymphoma. Blood Adv. 2022;6(4):1143-1151. doi:10.1182/bloodadvances.2021006240 85. Leonard JP, Schuster SJ, Emmanouilides C, et al. Durable complete responses from therapy with combined epratuzumab and rituximab: final results from an international multicenter, phase 2 study in recurrent, indolent, non-Hodgkin lymphoma. Cancer. 2008;113(10):2714-2723. doi:10.1002/cncr.23890 86. Grant BW, Jung SH, Johnson JL, et al. A phase 2 trial of extended induction epratuzumab and rituximab for previously untreated follicular lymphoma: CALGB 50701. Cancer. 2013;119(21):3797-3804. doi:10.1002/cncr.28299 87. Morschhauser F, Flinn IW, Advani R, et al. Polatuzumab vedotin or pinatuzumab vedotin plus rituximab in patients with relapsed or refractory non-Hodgkin lymphoma: final results from a phase 2 randomised study (ROMULUS). Lancet Haematol. 2019;6(5):e254-e265. doi:10.1016/S2352-3026(19)30026-2 88. Diefenbach C, Kahl BS, McMillan A, et al. Polatuzumab vedotin plus obinutuzumab and lenalidomide in patients with relapsed or refractory follicular lymphoma: a cohort of a multicentre, single-arm, phase 1b/2 study. Lancet Haematol. 2021;8(12):e891-e901. doi:10.1016/S2352-3026(21)00311-2 89. Hutchings M, Mous R, Clausen MR, et al. Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an open-label, phase 1/2 study. Lancet Lond Engl. 2021;398(10306):1157-1169. doi:10.1016/S0140-6736(21)00889-8 90. Bannerji R, Arnason JE, Advani RH, et al. Odronextamab, a human CD20×CD3 bispecific antibody in patients with CD20-positive B-cell malignancies (ELM-1): results from the relapsed or refractory non-Hodgkin lymphoma cohort in a single-arm, multicentre, phase 1 trial. Lancet Haematol. 2022;9(5):e327-e339. doi:10.1016/S2352-3026(22)00072-2 91. Hutchings M, Morschhauser F, Iacoboni G, et al. Glofitamab, a Novel, Bivalent CD20-Targeting T-Cell-Engaging Bispecific Antibody, Induces Durable Complete Remissions in Relapsed or Refractory B-Cell Lymphoma: A Phase I Trial. J Clin Oncol Off J Am Soc Clin Oncol. 2021;39(18):1959-1970. doi:10.1200/JCO.20.03175 92. Subklewe M. BiTEs better than CAR T cells. Blood Adv. 2021;5(2):607-612. doi:10.1182/bloodadvances.2020001792 93. Tapia-Galisteo A, Compte M, Álvarez-Vallina L, Sanz L. When three is not a crowd: trispecific antibodies for enhanced cancer immunotherapy. Theranostics. 2023;13(3):1028-1041. doi:10.7150/thno.81494 94. Wu L, Seung E, Xu L, et al. Trispecific antibodies enhance the therapeutic efficacy of tumor-directed T cells through T cell receptor co-stimulation. Nat Cancer. 2020;1(1):86-98. doi:10.1038/s43018-019-0004-z 95. Yao Y, Hu Y, Wang F. Trispecific antibodies for cancer immunotherapy. Immunology. 2023;169(4):389-399. doi:10.1111/imm.13636 96. Fayad L, Offner F, Smith MR, et al. Safety and clinical activity of a combination therapy comprising two antibody-based targeting agents for the treatment of non-Hodgkin lymphoma: results of a phase I/II study evaluating the immunoconjugate inotuzumab ozogamicin with rituximab. J Clin Oncol Off J Am Soc Clin Oncol. 2013;31(5):573-583. doi:10.1200/JCO.2012.42.7211 97. Kolstad A, Illidge T, Bolstad N, et al. Phase 1/2a study of 177Lu-lilotomab satetraxetan in relapsed/refractory indolent non-Hodgkin lymphoma. Blood Adv. 2020;4(17):4091-4101. doi:10.1182/bloodadvances.2020002583 98. Palomba ML, Till BG, Park SI, et al. Combination of Atezolizumab and Obinutuzumab in Patients with Relapsed/Refractory Follicular Lymphoma and Diffuse Large B-Cell Lymphoma: Results from a Phase 1b Study. Clin Lymphoma Myeloma Leuk. 2022;22(7):e443-e451. doi:10.1016/j.clml.2021.12.010 99. Morschhauser F, Ghosh N, Lossos IS, et al. Obinutuzumab-atezolizumab-lenalidomide for the treatment of patients with relapsed/refractory follicular lymphoma: final analysis of a Phase Ib/II trial. Blood Cancer J. 2021;11(8):147. doi:10.1038/s41408-021-00539-8 100. Czuczman MS, Hess G, Gadeberg OV, et al. Chemoimmunotherapy with ofatumumab in combination with CHOP in previously untreated follicular lymphoma. Br J Haematol. 2012;157(4):438-445. doi:10.1111/j.1365-2141.2012.09086.x 101. Westin JR, Chu F, Zhang M, et al. Safety and activity of PD1 blockade by pidilizumab in combination with rituximab in patients with relapsed follicular lymphoma: a single group, open-label, phase 2 trial. Lancet Oncol. 2014;15(1):69-77. doi:10.1016/S1470-2045(13)70551-5 102. Czuczman MS, Leonard JP, Jung S, et al. Phase II trial of galiximab (anti-CD80 monoclonal antibody) plus rituximab (CALGB 50402): Follicular Lymphoma International Prognostic Index (FLIPI) score is predictive of upfront immunotherapy responsiveness. Ann Oncol Off J Eur Soc Med Oncol. 2012;23(9):2356-2362. doi:10.1093/annonc/mdr620