Real-World Effectiveness of Chemoimmunotherapy and Novel Therapies for Patients With Relapsed/Refractory Aggressive Large B-Cell Lymphoma.

Introduction: Clinical trials provide meaningful data regarding the safety and efficacy of novel therapies but there is often a lag between the time of new drug approval and information on posttreatment clinical outcomes in real-world practice. This study evaluated clinical outcomes in a large real-world population of patients with relapsed and/or refractory large B-cell lymphoma (r/r LBCL) treated with chemoimmunotherapy or novel therapies in second or later lines of therapy (2L+).
Materials and Methods: Data from the Lymphoma Epidemiology of Outcomes (LEO) Consortium of Real-World Evidence (CReWE) cohort (1/1/2015-2/15/2023) were analyzed. Patients' demographic and clinical characteristics were described and response rates, duration of response, progression-free survival, and overall survival were evaluated. Multivariable Cox proportional hazards regression models were used to assess associations between patient clinical characteristics and outcomes.
Results: The 2L+ cohort included patients treated with chemoimmunotherapy (N = 593), lenalidomide-based therapy (n = 60), polatuzumab vedotin-based therapy (N = 116), tafasitamab-based therapy (N = 55), and loncastuximab tesirine (N = 42). Most patients who received prior chimeric antigen receptor T-cell therapy (CAR-T) were refractory to the treatment. Across all patients, overall response rates were <50%, with one-quarter achieving complete response and median duration of response and overall survival were short (<6 and <10 months, respectively) among patients treated with chemoimmunotherapy or novel therapies. The prognosis was worse for patients who had previously received CAR-T. Primary refractory status, high-risk disease, and failing 3 or more lines of therapy were significantly associated with worse outcomes.
Conclusion: Patients with r/r LBCL have unfavorable outcomes and need more effective treatment alternatives.
Competing Interests: Disclosure LJN has received honoraria for participating in the advisory boards of AbbVie, AstraZeneca, BMS, Genentech, Genmab, Gilead/Kite, Incyte, Ipsen, Janssen, Merck, Novartis, Regeneron, and Takeda; and research support from BMS, Caribou Biosciences, Genentech, Genmab, Gilead/Kite, IGM Biosciences, Janssen, Merck, Novartis, and Takeda. YW has received research funding (to his institution) from AbbVie, Eli Lilly, Genentech, Genmab, Incyte, InnoCare, LOXO Oncology, MorphoSys, and Novartis; compensation (to his institution) for serving on the advisory boards of AstraZeneca, BeiGene, Eli Lilly, Genmab, Incyte, InnoCare, Jansen, Kite, LOXO Oncology, and TG Therapeutics; compensation (to his institution) for providing consultancy services to AbbVie and Innocare; and honoraria (to his institution) from Kite. TMH is on the Data Monitoring Committees of Eli Lilly & Company and Seagen; and has received research funding (to his institution) from Genentech/Roche, Genmab, and Sorrento. DC has received honoraria from Beigene and Ono, and research funding from BMS, Genmab, Ipsen, Morphosys, and Ono. BSK has served as a consultant for ADC Therapeutics, Celgene/BMS, and Genentech/Roche. BKL has received compensation from Genentech/Roche and MEI Inc. for Data Safety Monitoring Board participation, and for participating in the advisory board of Genentech/Roche; and has received research funding from AstraZenenca, Genentech/Roche, and Genmab. JLK has received honoraria for providing consultancy services to or compensation for participating in the advisory boards of AbbVie and Beigene; and research support from Viracta Therapeutics. JBC has served as an advisor to ADCT, AstraZeneca, Beigene, Janssen, Kite/Gilead, and Loxo/Lilly; and has received research funding from AstraZeneca, BMS/Celgene, Genentech, Loxo/Lilly, Novartis, and Takeda. PM has served as a consultant for AbbVie, AstraZeneca, Beigene, Daiichi Sankyo, Epizyme, Genentech, Janssen, and Merck. ISL is a current employee of the University of Miami; has received honoraria from Adaptive; has served in a consulting or advisory role for Lymphoma Research Foundation; has received research funding from the National Cancer Institute; and has received compensation for teaching from Kyowa Kirin. CC has served as consultant for and has received honoraria from AbbVie, BMS, Genentech, and Mashup Media; has received research funding from Genentech, Genmab, and Gilead; and has had leadership roles in Follicular Lymphoma Cures Foundation and American Society of Hematology. SA has received research funding (to his instituition) from AstraZeneca, Beigene, Genentech, Genmab, and Regeneron; has served on the Speakers Bureau for Genentech and Total CME; and has acted as a consultant/advisor for Abbvie, ADC Therapeutics, Beigene, Fate Therapeutics, Genentech, and Seattle Genetics. MAL has received compensation from Genmab and GNE. MJM has received research funding from BMS, Genmab, and Roche/Genentech; is on the advisory board of AstraZeneca; and has received compensation (to his institution) for providing consultancy services to BMS. LH, CG, RR, and MSD are employees of Analysis Group Inc., which provided paid consultancy services to Genmab, the study sponsor. AM, TW, MJ, and AK are current employees of Genmab and hold stock options. AW and RK are current employees of AbbVie and hold stock options. CRF has served as a consultant for AbbVie, Bayer, BeiGene, Celgene, Denovo Biopharma, Foresight Diagnostics, Genentech/Roche, Genmab, Gilead, Karyopharm, N-Power Medicine, Pharmacyclics/Janssen, SeaGen, and Spectrum; holds stock or stock options for Foresight Diagnostics and N-Power Medicine; and has received research funding from 4D, AbbVie, Acerta, Adaptimmune, Allogene, Amgen, Bayer, BostonGene, Celgene, Cellectis EMD, Gilead, Genentech/Roche, Guardant, Iovance, Janssen Pharmaceutical, Kite, Morphosys, Nektar, Novartis, Pfizer, Pharmacyclics, Sanofi, Takeda, TG Therapeutics, Xencor, and Ziopharm as well as Burroughs Wellcome Fund, Cancer Prevention and Research Institute of Texas RR190079: CPRIT Scholar in Cancer Research; Eastern Cooperative Oncology Group, National Cancer Institute, and V Foundation. All the other authors declared that they have no conflicts of interest to declare.
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