Relevant bibliographies by topics / Immune-related adverse effects (irAEs)

Academic literature on the topic 'Immune-related adverse effects (irAEs)'

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Published: 10 December 2022
Last updated: 28 January 2023

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Journal articles on the topic "Immune-related adverse effects (irAEs)"

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Naing, Aung, Joud Hajjar, James L. Gulley, Michael B. Atkins, Gennaro Ciliberto, Funda Meric-Bernstam, and Patrick Hwu. "Strategies for improving the management of immune-related adverse events." Journal for ImmunoTherapy of Cancer 8, no. 2 (December 2020): e001754. http://dx.doi.org/10.1136/jitc-2020-001754.

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With the advent of immunotherapeutic agents, durable and dramatic responses have been observed in several hard-to-treat malignancies, outlining a roadmap to conquering cancer. Immune checkpoint inhibitors (ICPi) are a class of immunotherapeutic agents that attack the tumor cells by reinvigorating the suppressed immune system. However, the unbridled T-cell activity disrupts the immune homeostasis and induces a unique spectrum of side effects called immune-related adverse events (irAEs) in a significant proportion of patients. These irAEs are distinct from the side effects produced by traditional chemotherapeutic agents. Although majority of irAEs are manageable with corticosteroids and other immunosuppressive agents, life-threatening and fatal events have been reported. In the absence of predictive biomarkers to identify patients at risk for irAEs and standardized approach to detect, report, and treat irAEs, management of irAEs has been challenging to the patients, caregivers and the healthcare providers alike. With increasing use of ICPis for treatment of various cancers, the incidence of irAEs will undoubtedly increase. There is a compelling need to develop measures to effectively manage irAEs, both in the community settings and in cancer centers alike. To this end, in this paper, we propose several strategies, such as providing patient education, harmonizing irAE management guidelines, standardizing reporting of irAEs, optimizing the choice of immunosuppressive agents, conducting preclinical, clinical and translational studies to better understand irAEs, including high-risk patients, incorporating diagnostic tools to personalize irAE management using wireless technology and digital health, providing a platform to hear the missing patient’s voice, and sharing evolving data to improve the management of irAEs.
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Reynolds, Kerry Lynn, Justine Vanessa Cohen, Sienna Durbin, Molly Thomas, Michael Dougan, Holly S. Martinson, Alex Faje, et al. "Inpatient admissions related to immune-related adverse effects (irAE) among patients treated with immune checkpoint inhibitors for advanced malignancy: A tsunami is coming, but are we ready?" Journal of Clinical Oncology 36, no. 5_suppl (February 10, 2018): 127. http://dx.doi.org/10.1200/jco.2018.36.5_suppl.127.

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127 Background: Disruption of the immune system with immune checkpoint inhibitors can result in a multitude of immune-related adverse effects (irAE). While irAEs have been well-reported in clinical trials, the impact and magnitude of irAE’s in the real-world, particularly inpatient is unclear. Methods: Data was collected on patients with advanced malignancy who experienced a suspected irAE needing admission to an academic hospital (Feb 2011 to June 2017). Each case was reviewed comprehensively by minimum of two reviewers, including one sub-specialist. In addition, oncologists at our institution were surveyed regarding their confidence about managing patients with irAEs. Results: Over a span of 6 years, there were 343 hospitalizations for suspected irAEs and the majority (65%; N = 223) were confirmed irAEs that required treatment with immunosuppression or therapy stopped as result. The mean length of stay was 6.3 days (range 1 to 31 days), readmission rate for another irAE event 25%, total readmission rate 61.7%, and inpatient mortality 8%. The most common irAEs were enterocolitis (43.9%), pulmonary (16%), hepatic (15%), neurological (8.9%), endocrinopathies (7.1%), rheumatological (4%), dermatological (3%), cardiovascular (3%), renal (1.8%), and allergy (1.3%). Over the past 5 years, there was a significant increase in admissions due to irAEs (admissions in 2016 vs 2011, odds ratio = 3.07; p < 0.01). The Cancer Center survey (N = 26) revealed majority of oncologists do not feel very comfortable managing irAEs, and 48% felt that irAE complications should be managed on a different service. Conclusions: irAEs from immune checkpoint inhibitors can result in prolonged hospitalizations, high rate of readmissions, and mortality. The number of patients admitted due to irAEs has significantly increased by more than three-fold in the recent years, but majority of oncologists do not feel very comfortable managing irAEs. Consequently, there is a critical need for coordinated multidisciplinary approach, comprehensive provider education, and translational research program for early detection and intervention.
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Chen, Ru, Min Zhou, and Feng Zhu. "Immune Checkpoint Inhibitors Related to Cardiotoxicity." Journal of Cardiovascular Development and Disease 9, no. 11 (November 3, 2022): 378. http://dx.doi.org/10.3390/jcdd9110378.

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Immune checkpoint inhibitors (ICIs) have now emerged as a mainstay of treatment for various cancers. Along with development of ICIs, immune-related adverse effects (irAEs) have aroused wide attention. The cardiac irAE, one of the rare but potentially fatal effects, have been reported recently. However, the clinical comprehension of cardiac irAEs remains limited and guidelines are inadequate for cardio-oncologists to tackle the problem. In this review, we have summarized current classifications of, manifestations of, potential mechanisms of, and treatment for ICI-related myocardial injury in order to provide some clues for the understanding of cardiac irAEs in clinical work.
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Kawahira, Machiko, Shuji Kanmura, Keiko Mizuno, Kentaro Machida, Takao Ohtsuka, Masami Sato, Hideki Enokida, et al. "Effects of immune checkpoint inhibitor therapy resumption in patients with malignant tumors after moderate-to-severe immune-related adverse events." PLOS ONE 17, no. 4 (April 28, 2022): e0267572. http://dx.doi.org/10.1371/journal.pone.0267572.

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Background and aims Immune checkpoint inhibitors (ICIs) are used to treat several cancers, but they sometimes induce immune-related adverse events (irAEs). Patients with irAEs often have improved antitumor responses, but discontinuation of ICIs after irAEs is considered necessary. Resuming the use of ICIs after irAEs is preferable, but few studies have investigated the safety of ICI resumption after irAEs. Therefore, we evaluated the factors associated with the recurrence of irAEs after ICI resumption to investigate the safety of this approach. Methods In this observational study, we enrolled patients treated with ICIs from September 2014 to March 2020 at our institution. Patient characteristics, ICIs, grades of irAEs, ICI discontinuation or resumption rates, and recurrence rates of irAEs after ICI therapy were analysed. Results Two-hundred eighty-seven patients were included in the present study, and 76 patients experienced grade 2 or higher irAEs. Forty-two patients underwent ICI resumption after recovering from irAEs, and 13 of them had a recurrence of irAEs. Among those 13 patients, six had a recurrence of the same irAE, and seven experienced other irAEs. Ten of the 13 patients had grade ≥2 irAEs, and none had fatal irAEs. In the grade 2 or higher irAE group, more patients had irAEs associated with multiple organs and of initial grade ≥2 than those in the grade 1 and no recurrent irAEs group. Conclusions Patients with initial multisystemic irAEs and irAEs of grade ≥2 were more likely to experience relapse or develop new grade ≥2 irAEs after ICI resumption.
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Wang, QuanQiu, and Rong Xu. "Immunotherapy-related adverse events (irAEs): extraction from FDA drug labels and comparative analysis." JAMIA Open 2, no. 1 (October 15, 2018): 173–78. http://dx.doi.org/10.1093/jamiaopen/ooy045.

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Abstract Objectives Immune checkpoint inhibitors (ICIs) have dramatically improved outcomes in cancer patients. However, ICIs are associated with significant immune-related adverse events (irAEs) and the underlying biological mechanisms are not well-understood. To ensure safe cancer treatment, research efforts are needed to comprehensively detect and understand irAEs. Materials and methods We manually extracted and standardized irAEs from The U.S Food and Drug Administration (FDA) drug labels for six FDA-approved ICIs. We compared irAE profile similarities among ICIs and 1507 FDA-approved non-ICI drugs. We investigated how irAEs have differential effects on human organs by classifying irAEs based on their targeted organ systems. Finally, we identified broad-spectrum (nontarget-specific) and narrow-spectrum (target-specific) irAEs. Results A total of 893 irAEs were extracted. 31.4% irAEs were shared among ICIs as compared to the 8.0% between ICIs and non-ICI drugs. irAEs were resulted from both on- and off-target effects: irAE profiles were more similar for ICIs with same target than different targets, demonstrating the on-target effects; irAE profile similarity for ICIs with the same target is less than 50%, demonstrating unknown off-target effects. ICIs significantly target many organ systems, including endocrine system (3.4-fold enrichment), metabolism (3.7-fold enrichment), immune system (3.6-fold enrichment), and autoimmune system (4.8-fold enrichment). We identified 21 broad-spectrum irAEs shared among all ICIs, 20 irAEs specific for PD-L1/PD-1 inhibition, and 28 irAEs specific for CTLA-4 inhibition. Discussion and conclusion Our study presents the first effort toward building a standardized database of irAEs. The extracted irAEs can serve as the gold standard for automatic irAE extractions from other data resources and set a foundation to understand biological mechanisms of irAEs.
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Coschi, Courtney H., and Rosalyn A. Juergens. "The Price of Success: Immune-Related Adverse Events from Immunotherapy in Lung Cancer." Current Oncology 28, no. 6 (November 2, 2021): 4392–407. http://dx.doi.org/10.3390/curroncol28060373.

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Cancer immunotherapy has the goal of enhancing a patient’s intrinsic immune processes in order to mount a successful immune response against tumor cells. Cancer cells actively employ tactics to evade, delay, alter, or attenuate the anti-tumor immune response. Immune checkpoint inhibitors (ICIs) modulate endogenous regulatory immune mechanisms to enhance immune system activation, and have become the mainstay of therapy in many cancer types. This activation occurs broadly and as a result, activation is supraphysiologic and relatively non-specific, which can lead to immune-related adverse events (irAEs), the frequency of which depends on the patient, the cancer type, and the specific ICI antibody. Careful assessment of patients for irAEs through history taking, physical exam, and routine laboratory assessments are key to identifying irAEs at early stages, when they can potentially be managed more easily and before progressing to higher grades or more serious effects. Generally, most patients with low grade irAEs are eligible for re-challenge with ICIs, and the use of corticosteroids to address an irAE is not associated with poorer patient outcomes. This paper reviews immune checkpoint inhibitors (ICIs) including their mechanisms of action, usage, associated irAEs, and their management.
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Thapa, Bicky, Joanna Roopkumar, Ann S. Kim, Lorenzo Gervaso, Pradnya Dinkar Patil, Cassandra Calabrese, Alok A. Khorana, and Pauline Funchain. "Incidence and clinical pattern of immune related adverse effects (irAE) due to immune checkpoint inhibitors (ICI)." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e14151-e14151. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e14151.

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e14151 Background: ICIs have revolutionized outcomes in many advanced malignancies, however their use is associated with irAEs. Methods: An IRB-approved, retrospective chart review was done using the Cleveland Clinic pharmacy database. Patients were included who received six FDA approved (nivolumab, ipilimumab, pembrolizumab, atezolizumab, avelumab, or durvalumab) ICIs from July 2015 to December 2017. irAEs were identified from review of electronic medical records. Descriptive analysis was done to evaluate the incidence, pattern, and severity of irAEs. Results: A total of 1091 patients received ICI therapy, 651 (59.7%) were male, 958 (87.4%) white, 95 (8.7%) black. Lung cancer (540, 49.5%) comprised the majority of the cohort, followed by melanoma (152, 13.9%), and renal cell carcinoma (121, 11.1%). About 996 (91.3%) received treatment with only one ICI, 85 (7.8%) with 2 ICIs, and only 10 patients received 3 ICIs. A total of 487 (44.63%) patients encountered irAEs, 128 (11.73%) resulting in treatment cessation. Fatigue (152, 13.9%) was the most common, followed by dermatologic irAEs (131, 12%). Endocrine irAEs occurred in 108 (9.89%), GI toxicities, namely diarrhea and colitis, were seen in 92 (8.4%) and hepatotoxicity in 54 (4.94%). Other irAEs including rheumatologic, pneumonitis, renal, and neurological adverse effects were documented in 6.5%, 5.1%, 2.56%, and 2.01% respectively. Rare irAEs such as ocular toxicity, cardiac toxicity, and vasculitis were seen in 0.8%, 0.73%, and 0.54%, respectively. Compared with a pooled analysis from clinical trials (De Velasco G et al. Comprehensive Meta-analysis of Key irAEs from CTLA-4 and PD-1/PD-L1 Inhibitors in Cancer Patients) dermatologic irAEs and fatigue were less frequent; diarrhea/colitis, pneumonitis and rheumatologic irAEs were more frequent. Conclusions: irAEs on ICI therapy are very common. Awareness of the relative frequencies of various irAEs, particularly severe and rare irAEs, in a real-world setting can help improve quality of care for cancer patients receiving ICI. [Table: see text]
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Kapoor, Akhil, Vanita Noronha, Vijay Maruti Patil, Amit Joshi, Nandini Sharrel Menon, and Kumar Prabhash. "Association of immune-related adverse effects and survival in responders treated with immune checkpoint inhibitors." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e15172-e15172. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e15172.

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e15172 Background: The development of immune-related adverse effects (irAEs) can corroborate with the response to immune checkpoint inhibitors (ICIs). However, there is very limited data on the association of irAEs with survival in patients who have shown response to ICIs. Methods: This study is a retrospective audit of prospectively collected database of patients who received ICIs for advanced solid tumors. Responders were defined as patients who attained best response of either complete response (CR) or partial response (PR). Time-to-event analysis was done using Kaplan-Meier estimator and hazard ratio was calculated by using Cox proportional model. Results: A total of 155 patients who received ICI during the specified period were evaluated for this study. The response rate was 19.4%. One year OS for responders was 75.6% (SD 8.8) versus 26.1% (SD 5.1). The median OS for patients who developed irAE was 12.3 months (95% CI: 8.9-15.6) while it was not reached for patients without irAE (HR 10.5, 95% CI 1.2-NR, p=0.007). One-year OS for the corresponding group of patients was 53.6% (SD 15.6) versus 92.9% (SD 6.9), respectively. Conclusions: This study reports negative association of immune-related adverse effects and survival in responding patients of solid tumors treated with immune checkpoint inhibitors. [Table: see text]
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Rodriguez, Benigno, José Fabián Martínez-Herrera, Lorena López Zepeda, Guillermo Olivares, Alberto Villalobos, Fernando Perez, Christian Patricio Camacho Limas, et al. "Association of immune-related adverse events with immune-checkpoint inhibitors and treatment response in melanoma patients." Journal of Clinical Oncology 40, no. 16_suppl (June 1, 2022): e21522-e21522. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.e21522.

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e21522 Background: Immune-related adverse effects (irAE´s) of immune-checkpoint inhibitors (ICIs) have been linked with a better treatment response in melanoma patients, especially cutaneous toxicities. However, little is known regarding other irAE´s which is important as they can be used as clinical markers of an adequate therapeutical response. Methods: We conducted a retrospective study on patients who were diagnosed with melanoma and received treatment with ICI´s between January 2015 until December 2021, immune related adverse events and their relationship with overall survival in melanoma patients treated with ICIs was the main objective of this study. Results: 53 records of patients with advance melanoma treated with ICIs between january 2016 to december 2021, demographic characteristics were as follow: 64.2% were male, mean age at diagnoses was 60.3 years, 41.5% had smoking history and 15.1% were Jewish. At diagnosis 73.6% of patients had a good functional status (ECOG 0-1). The most common histological subtypes were epithelioid (34%), and nodular (22.6%). Lung metastases was the most common affected site (49.1%), followed by brain 43.4% and non-regional nodes 42.5%. BRAF mutations was determined in 81.1% of the biopsies and 36% of them being V600E mutation. ICI´s was the preferred first line treatment in 83% of cases, median number of administered cycles were 6 (range 1-54 cycles), 60.4% of patients received pembrolizumab, 37.7% nivolumab plus ipilimumab, 20.8% nivolumab monotherapy and 5.7% ipilimumab. Throughout the studied period IrAE´s were reported in 34% of patients with 66.7% of them being grade 1-2 and 33.3% grade 3-4. The most common IrAE’s: vitiligo 38.8%, hypothyroidism22% and 3.8% pneumonitis. Median PFS at 12 months and OS was significantly better in the group of patients with irAE´s: Patients who develop an irAE´s are 7 times more likely to be disease free at 12 months and 4.1 times more likely to have a longer OS regardless of severity and type of toxicity. The impact of developing irAEs is significantly important for PFS (HR: 11.9, CI 95%: 3.28-4.71) as median PFS was not yet reached in this group. Conclusions: Development of irAEs is associated with favorable outcomes to ICIs with patients being 7 times more likely to be 12-month disease free and 4.1 times more likely to have a longer OS. irAEs can be used as clinical markers of an adequate treatment response.[Table: see text]
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Kim, Sarah, A. Dimitrios Colevas, Stephanie Tse, Sandy On, and Edna Cheung. "Immune-related adverse effects of long-term PD-1/PD-L1 inhibtor treatment." Journal of Clinical Oncology 40, no. 16_suppl (June 1, 2022): 2661. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.2661.

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2661 Background: Immune-related adverse effects (irAE) are autoimmune-like toxicities caused by immune checkpoint inhibitor (ICI) treatment and often necessitate interventions such as corticosteroids, treatment interruptions/discontinuation, or hospital admission. Although ICI related irAEs are well described in literature, data on the toxicity profile associated with long-term ICI use remains limited. Since the optimal duration of therapy with ICI agents is currently unknown, it is crucial to assess the risks of long-term ICI use. Methods: This was a retrospective, observational, single-center study of adult oncology patients who received at least 1 year of programed death 1 (PD-1) inhibitor or programmed death ligand-1 (PD-L1) inhibitor treatment. The objective of this study was to characterize late-onset irAEs defined as greater than 1 year with long-term ICI treatment. Clinically significant irAEs were defined as those requiring corticosteroid treatment, hospital admission, treatment interruption or treatment discontinuation. This study included patients who received at least 1 year of nivolumab, pembrolizumab, atezolizumab or durvalumab between January 2016 and September 2021. Disease states included head and neck cancer, renal cell carcinoma, non-small cell lung cancer, and melanoma. Patients with concurrent exposure to other treatment such as chemotherapy, radiation, surgery, tyrosine kinase inhibitors and monoclonal antibodies while on ICI treatment were included in the study. Exclusion criteria included patients with treatment breaks of greater than 6 months, two malignancies undergoing active treatment, and treatment administration outside of the study center. Results: Of 282 patients assessed, 143 met study inclusion criteria. The median ICI treatment duration was 19 months (IQR 14-27). There was a 30% incidence of late-onset irAEs, of which 22% were clinically significant. Most late-onset irAEs were low in severity, as 45 (90%) were grade 1-2 and 5 (10%) were grade 3. The most common late-onset irAEs were pulmonary (8%) and gastrointestinal (7%). Univariate analysis suggests risk factors potentially associated with late-onset irAEs include concurrent exposure to additional therapies during ICI treatment and past medical history of rheumatologic disease. Conclusions: Although the optimal duration of ICI therapy is unknown, this study suggests that long-term ICI use was associated with a low but notable incidence of toxicities, of which most were low in severity. [Table: see text]
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Books on the topic "Immune-related adverse effects (irAEs)"

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Drug-induced immune diseases. Amsterdam: Elsevier, 1990.

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Immunotoxicity testing: Methods and protocols. New York, NY: Humana Press, 2010.

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Dietert, Rodney R. Immunotoxicity Testing: Methods and Protocols. Humana Press, 2016.

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Coyle, Patricia K. Immune-mediated Disorders of the Central Nervous System. Edited by Emma Ciafaloni, Cheryl Bushnell, and Loralei L. Thornburg. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190667351.003.0010.

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This chapter reviews pregnancy in multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and acute transverse myelitis (ATM) syndrome. MS is a major acquired disease of young adults, with a rising female predominance. MS has no direct negative consequences on fertility or pregnancy. Pregnancy has a profound effect on MS, with decrease in disease activity during the last trimester counteracted by a three-month postpartum increase in disease activity. With the development of disease-modifying therapies, important questions arise about washout periods, the feasibility and risks of treating during pregnancy and breastfeeding, and the potential of treatment-related adverse fetal effects. Fortunately, there is good information to counsel women with MS. Neuromyelitis Optica Spectrum Disorder (NMOSD) is a neuroimmune channelopathy. It is a distinct disorder from MS. NMOSD disease activity is not favorably affected by pregnancy. The postpartum period has real risk for disabling attacks. This influences recommendations about breastfeeding and how quickly to resume therapy postpartum. Acute transverse myelitis (ATM) syndrome can occur in both MS and NMOSD but can also be due to other disorders. Workup and treatment of ATM during pregnancy is reviewed, as well as implications for delivery.
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Book chapters on the topic "Immune-related adverse effects (irAEs)"

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Meara, Alexa Simon, and Leonard H. Calabrese. "Management of Rheumatic Immune-Related Adverse Events (irAEs): General Principles." In Rheumatic Diseases and Syndromes Induced by Cancer Immunotherapy, 309–21. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-56824-5_14.

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E. Omar, Nabil, Hebatalla M. Afifi, Arwa O. Sahal, Rana Mekkawi, and Hazem Elewa. "The Flip of the Coin of Personalized Cancer Immunotherapy: A Focused Review on Rare Immune Checkpoint Related Adverse Effects." In Immune Checkpoint Inhibitors - New Insights and Recent Progress [Working Title]. IntechOpen, 2022. http://dx.doi.org/10.5772/intechopen.107833.

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Immune checkpoint inhibitors (ICIs) are a type of cancer immunotherapy that has provided a tremendous breakthrough in the field of oncology. Currently approved checkpoint inhibitors target the cytotoxic T-lymphocyte-associated protein 4 (CTLA4), programmed death receptor-1 (PD-1), and programmed death-ligand 1(PD-L1). One of the most known complications of these advances is the emergence of a new spectrum of immune-related adverse events (irAEs). In this chapter, we will focus on selected rare or very rare irAEs, shedding the light on the other side of the coin of personalized cancer immunotherapy. We will also discuss general management approach of irAEs with an in-depth look on each one of these rare irAEs. The chapter will also cover principles of immunotherapy rechallenge post-occurrence of irAEs, and the impact of irAEs incidence on the efficacy of ICI. We will discuss some of the rare or very rare irAEs including cutaneous irAEs, immune-mediated Hypophysitis, hematological irAEs, ophthalmic irAEs, checkpoint inhibitor pneumonitis (CIP), neurologic irAEs, infectious irAEs, and cardiac irAEs. This chapter tried to highlight the significance of identifying emerging rare and very rare irAEs while considering initial assessments and management approaches identified in various clinical practice guideline and primary literature data.
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Rivera-Grana, Erick, and Stephanie M. Llop. "Immunotherapy-Associated Uveitis." In Eye Diseases - Recent Advances, New Perspectives and Therapeutic Options [Working Title]. IntechOpen, 2022. http://dx.doi.org/10.5772/intechopen.106442.

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Novel immunotherapies used to treat some cancers, such as checkpoint inhibitors and target therapies of B-RAF protooncogene and mitogen-activated protein kinase (BRAF/MEK), have been strongly associated with adverse events related to immune dysregulation. These effects are known as immune-related adverse events (irAEs). Uveitis is among the known irAEs, and it occurs in approximately 1% of patients using these therapies. The uveitis observed in these patients ranges from anterior, intermediate, to panuveitis. If irAEs are severe, current recommendations are to stop immunotherapy treatment and simultaneously treat the uveitis with steroids (local or systemic). These oncologic immunotherapies have proved to show positive results in cancer treatment. Their use has increased with time, showing ocular side effects that were not reported previously. It is important that ophthalmologists and non-ophthalmologists are aware of these agents and their potential ocular side effects for timely diagnosis and adequate management. This chapter will review different immunotherapies and their potential ocular manifestations and how to diagnose, monitor, and manage these patients.
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Moran, Carla. "Endocrine Complications of Biological Cancer Therapies." In Oxford Textbook of Endocrinology and Diabetes 3e, edited by John A. H. Wass, Wiebke Arlt, and Robert K. Semple, 1774–78. Oxford University Press, 2021. http://dx.doi.org/10.1093/med/9780198870197.003.0218.

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In recent years, modulation of cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) pathways has resulted in significant improvements in cancer outcomes. Immune-related adverse events (IrAEs), including endocrinopathies, are common toxicities associated with use of these immune checkpoint inhibitors, with agents affecting the CTLA-4 pathway typically causing hypophysitis, and those affecting the PD-1 pathway most commonly causing thyroid dysfunction. Notably, due to non-specific and ill-defined symptoms, these endocrine-associated IrAEs can escape detection, such that surveillance for these side effects is warranted. Although these endocrinopathies may be irreversible, they are rarely life-threatening and there is emerging evidence that individuals experiencing such side effects have better cancer outcomes. With likely increasing use of these agents over the coming decade, endocrinologists can expect to diagnose and manage these side effects more frequently.
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Patel, Anush, Haisam Abid, and Amrat Kumar. "The Endocrinological Side Effects of Immunotherapies." In Advances in Precision Medicine Oncology. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.96491.

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The use of immunotherapies is gaining importance in the treatment of advanced malignancies. There are many checkpoints in the immune system which prevents T-cells from attacking one’s own body cells. The cancer cells can camouflage from the T-cells and the immune system is unable to mount an effective anti-tumor response. The immunotherapies, mainly monoclonal antibodies anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4), anti-programmed cell death protein-1 (PD-1) and anti-PD-1 ligand molecules (PD-L1 and L2) reactivate the immune system to act against cancerous cells but they can also cause T-cells to attack healthy cells causing various autoimmune diseases, which are known as immune related adverse events (irAEs). Current clinical data shows increased incidence of pituitary disorders with CTLA4 inhibitors and thyroid dysfunction in patients with PD-1/PD L-1 1 blockade. There have also been association of type 1 diabetes mellitus and primary adrenal insufficiency in patients with immune check point inhibitors. In this chapter we will discuss the incidence, characteristic findings, diagnosis and management of various endocrinological side effects due to targeted immunotherapies used in various malignancies.
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Memis Bilgin, Yavuz. "Clinical Effects and Possible Mechanisms of Transfusion-Related Immunomodulation." In Blood Donation and Transfusion [Working Title]. IntechOpen, 2022. http://dx.doi.org/10.5772/intechopen.107228.

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Allogeneic blood components are commonly transfused in trauma, surgery, and intensive care units and are related with adverse effects, such as postoperative infections, multi-organ failure, and mortality. The adverse effects of blood transfusions on the immune system are called as transfusion-related immunomodulation (TRIM). Many clinical trials are conducted to show the clinical effects of TRIM. They found in different clinical settings controversial results. There are many possible mechanisms of TRIM. Although until now, the exact mechanisms are not elucidated resulting in a challenge to unravel this complex interaction between immunomodulation and clinical events leading to morbidity and mortality. It has been postulated that allogeneic leukocytes are associated with the clinical adverse effects of TRIM that predominantly is observed in high-risk patients as cardiovascular surgery. Allogeneic leukocytes could activate inflammation cascade leading to adverse events in high-risk patients. Also other blood components as red cells, plasma, and platelets can play a role in the development of inflammatory complications after blood transfusions. In this review, we will discuss the clinical effects and the possible mechanisms of TRIM in relation with allogeneic leukocytes and mediators derived from allogeneic blood transfusions.
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Bhattacharyya, Joya, and Arthur Kaser. "Immune disorders of the gastrointestinal tract." In Oxford Textbook of Medicine, edited by Jack Satsangi, 2783–96. Oxford University Press, 2020. http://dx.doi.org/10.1093/med/9780198746690.003.0292.

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Immune homeostasis in the gut is the result of a delicate balance between peaceful coexistence with commensal microbiota, immunomodulatory effects of dietary antigens, and appropriate responses to pathogens. Immune disorders of the gut arise when defects in the integrity of these components lead to a dysregulated immune response to the commensal environment. Primary immunodeficiency syndromes can present with intestinal inflammation but are commonly characterized by an increased susceptibility to infections in childhood. Secondary immunodeficiency can occur in a protein-losing enteropathy where loss of immunoglobulins and lymphocytes increase susceptibility to infections, or as a result of metabolic diseases (e.g. diabetes or liver cirrhosis), infections (e.g. HIV), or drugs (e.g. chemotherapy). Immunosuppressive medication can not only lead to secondary immunodeficiency but in the context of neutropenia, cytotoxic gastrointestinal mucosal injury can lead to neutropenic typhlitis. Graft-versus-host disease arises from host antigen-presenting cells engaging with donor T cells and triggering an inflammatory cascade. Immunotherapy with checkpoint inhibitors can have significant gastrointestinal immune-related adverse effects, most notably enterocolitis. Autoimmune diseases can impact gastrointestinal function. Autoimmune dysautonomia can result in gastrointestinal-specific dysmotility and systemic IgG4-related disease can lead to autoimmune pancreatitis. Systemic autoimmune diseases can have gastrointestinal manifestations related to the primary autoimmune process or as an adverse effect of treatment. Hypersensitivity reactions to dietary antigens (e.g. peanuts) result in food allergies and can be either IgE or non-IgE mediated. Food intolerance which is not immunologically mediated is the result of pharmacological (e.g. monosodium glutamate), enzyme-related (e.g. lactose intolerance), or noncoeliac gluten sensitivity. Eosinophilic gastrointestinal tract disorders are often associated with a food allergen: treatment is with steroids and avoidance of the allergen.
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Burton, Rosie, and Ana Houston. "HIV medicine." In Oxford Handbook of Tropical Medicine 5e, 69–142. Oxford University Press, 2021. http://dx.doi.org/10.1093/med/9780198810858.003.0003.

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Epidemiology, Virology and immunology, infection, Antiretroviral therapy, opportunistic infections, Antiretroviral drugs, doses and adverse effects, viral failure, Common clinical problems in HIV, HIV-related malignancy, Immune Reconstitution Inflammatory Syndrome (IRIS), HIV prevention strategies, Prevention of mother to child transmission (PMTCT), Post-exposure prophylaxis
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Molitch, Mark E., and Jelena Kravarusic. "Lymphocytic Hypophysitis and other Inflammatory Conditions of the Pituitary." In Oxford Textbook of Endocrinology and Diabetes 3e, edited by John A. H. Wass, Wiebke Arlt, and Robert K. Semple, 304–12. Oxford University Press, 2021. http://dx.doi.org/10.1093/med/9780198870197.003.0035.

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Inflammatory conditions of the pituitary are very rare, and in presentation similar to adenomas by symptoms of expanding sellar mass, visual disturbances, and pituitary hormone deficiencies. They can be of various origin, autoimmune such as lymphocytic hypophysitis, secondary, as a part of immune-related adverse effects, or a part of a systemic disease such as IgG4-related disease. Due to their uncommon occurrence, pathogenesis is still largely unknown and therapies are not well established. However, as there is increase in awareness, the rate of diagnosis is increasing. This chapter outlines current knowledge on these rare conditions, approach to diagnosis with careful attention to epidemiology which often helps guide prioritization of the differential diagnosis and summarizes therapeutic approaches as they are developing.
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Perera, Frederica. "A Myriad of Health Impacts from Fossil Fuel." In Children's Health and the Peril of Climate Change, 46—C3.S27. Oxford University PressNew York, 2022. http://dx.doi.org/10.1093/oso/9780197588161.003.0003.

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Abstract Chapter 3 reviews the diverse health effects in children attributable to fossil fuel–related air pollution and climate change, individually and combined. It describes the links between air pollution and adverse birth outcomes, cognitive and behavioral problems, mental health disorders, asthma, and effects on the immune system. The chapter also reviews the toll on children from weather disasters, heat, fires, drought and malnutrition, infectious disease, forced migration, and displacement. It explores the mechanisms involved and then focuses on the separate and cumulative effects of these exposures on early brain development and mental health, noting the potential long-term effects. It presents examples of synergy between air pollution and climate change that augment the harm. It describes the additional effects of toxic substances derived from petrochemicals. By reviewing this vast body of research, the chapter shows that all children are being affected in multiple ways.
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Conference papers on the topic "Immune-related adverse effects (irAEs)"

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Sklodowski, Kamil, Vito Dozio, Roberta Poli, Andrés Lanzós, Silvia Lopez-Lastra, Kristina Beeler, and Emanuela Romano. "Abstract 1615: Immune-related adverse effects (irAEs) associated proteomic profile in late-stage NSCLC patients after PD-1 blockade." In Proceedings: AACR Annual Meeting 2021; April 10-15, 2021 and May 17-21, 2021; Philadelphia, PA. American Association for Cancer Research, 2021. http://dx.doi.org/10.1158/1538-7445.am2021-1615.

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Kaakour, Dalia, Matthew Slaught, Armon Azizi, Gianna Kroening, Jennifer Valerin, and Nataliya Mar. "1247 Distribution of immune-related adverse events (irAEs) in solid malignancies." In SITC 37th Annual Meeting (SITC 2022) Abstracts. BMJ Publishing Group Ltd, 2022. http://dx.doi.org/10.1136/jitc-2022-sitc2022.1247.

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Ennis, D., F. To, and S. Jamal. "THU0615 Immune related adverse events (IRAES) associated with checkpoint inhibitors: 12 cases from a single centre." In Annual European Congress of Rheumatology, EULAR 2018, Amsterdam, 13–16 June 2018. BMJ Publishing Group Ltd and European League Against Rheumatism, 2018. http://dx.doi.org/10.1136/annrheumdis-2018-eular.6009.

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Liu, Jing, Stephten J. Blake, Kirsten A. Fairfax, Michelle C. R. Yong, Stacey Allen, Mark J. Smyth, and Michele W. L. Teng. "Abstract B122: A preclinical mouse model to assess antitumor efficacy and development of immune related adverse events (irAEs) following combination immunotherapies." In Abstracts: CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/2326-6074.cricimteatiaacr15-b122.

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Davis, Andrew A., Jonghanne Park, Leeseul Kim, Gahyun Gim, Wade T. Iams, Michael S. Oh, Robert W. Lentz, et al. "Abstract 5527: Serum proteomic scores for understanding the mechanisms of immune-related adverse events (irAEs) in non-small cell lung cancer." In Proceedings: AACR Annual Meeting 2020; April 27-28, 2020 and June 22-24, 2020; Philadelphia, PA. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/1538-7445.am2020-5527.

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Richter, M. D., C. S. Crowson, L. A. Kottschade, H. D. Finnes, S. N. Markovic, and U. Thanarajasingam. "SAT0588 Rheumatologic immune-related adverse effects of checkpoint inhibitor therapy: a single centrecohort of 29 patients." In Annual European Congress of Rheumatology, EULAR 2018, Amsterdam, 13–16 June 2018. BMJ Publishing Group Ltd and European League Against Rheumatism, 2018. http://dx.doi.org/10.1136/annrheumdis-2018-eular.2645.

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Kandolf Sekulović, Lidija. "TOXICITIES OF TARGETED THERAPY AND IMMUNE-RELATED ADVERSE DRUG REACTIONS OF IMMUNOTHERAPY IN THE TREATMENT OF METASTATIC MELANOMA." In Okrugli sto s međunarodnim učešćem "Melanom". Akademija nauka i umjetnosti Bosne i Hercegovine, 2018. http://dx.doi.org/10.5644/pi2019.180.04.

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Targeted therapy and immunotherapy changed the treatment landscape for metastatic melanoma, which is chemotherapy resistant cancer. In pre-innovation era, the overall survival of patients with metastatic melanoma was 6 months, while today 5-year overall survival rate of 34% (and 50% in good prognostic groups) is evident. However, both treatments have their side effects, and cutaneous are the most frequent. Treating physicians in oncology centres, but also primary care specialists, need to be aware of their spectrum which differs for each class of drug: BRAF inhibitors, MEK inhibitors and immunotherapy with anti-PD1 and anti-CTLA4. While BRAF inhibitors have the most prominent adverse effects which are class specific, there are also drug-specific adverse effects. For example, vemurafenib causes photosensitivity, which is not specific for dabrafenib, while dabrafenib induces pyrexia, that occurs much less frequently with other BRAF inhibitors. Cutaneous rash and cutaneous neoplasms which develop due to paradoxical activation of RAS signalling are described with BRAF inhibitor monotherapy. These side-effects are much less common in combination therapy with BRAF and MEK inhibitor, but MEK inhibitor itself causes characteristic acneiform eruption, and serous retinopathy. Immune related adverse drug reactions are a hallmark of the immune checkpoint inhibitor immunotherapy, which can affect every organ system, and most commonly skin, lungs and gastrointestinal system, with differential frequencies recorded with anti-CTLA4 therapy and anti PD-1 therapy. Skin reactions most frequently include pruritus and eczematous reactions, as well as vitiligo-like hypopigmentation, which is linked Melanom 45 to the better response to treatment. In this review, frequent and rare side effects are presented, as well as the current algorithms for their treatment.
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Kostine, M., E. Mauric, L. Rouxel, T. Barnetche, R. Veillon, F. Martin, C. Dutriaux, et al. "OP0088 Immune-related adverse events of cancer immunotherapy – when inflammatory side effects are associated with survival: a single-centre prospective cohort study." In Annual European Congress of Rheumatology, EULAR 2018, Amsterdam, 13–16 June 2018. BMJ Publishing Group Ltd and European League Against Rheumatism, 2018. http://dx.doi.org/10.1136/annrheumdis-2018-eular.3783.

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MONBRUN, Mathilde, Léo Grassion, Elodie Blanchard, Rémi Veillon, Maeva Zysman, and Chantal Raherison. "Influenza and Pneumococcal vaccination effects on the immune-related adverse events in patients under immunotherapy for an advanced stage non-small cell lung cancer." In ERS International Congress 2021 abstracts. European Respiratory Society, 2021. http://dx.doi.org/10.1183/13993003.congress-2021.pa2303.

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