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Chimeric antigen receptor T cell therapy in octogenarians with B cell lymphoma: a real-world US multicenter collaborative study

Abstract

Older patients with lymphoma are typically underrepresented in clinical trials with chimeric antigen receptor T cell (CAR T) therapy. In this multicenter, observational study we aimed to assess the safety and efficacy of standard CD19 CAR T in patients 80 years of age or older. At total of 88 patients, median age 82 (range, 80-89) years, were included. Diffuse large B cell lymphoma (DLBCL) (N = 60, 68.2%) represented the most common histology. Patients were treated mostly with axicabtagene ciloleucel (N = 41, 46.6%) followed by lisocabtagene maraleucel (N = 25, 28.4%). Cytokine release syndrome (CRS) (any grade) was seen in 68 (77.3%) and 51 (58%) developed immune effector cell-associated neurotoxicity syndrome (ICANS). Incidence of grade 3-4 CRS and ICANS were 7.4% and 31.4%, respectively. For patients with DLBCL/tFL, the 1-year NRM, relapse, PFS, and OS were 11.6%, 40.8%, 47.6%, and 61.2%, respectively. We conclude that CAR T is feasible and effective in patients 80 years or older with B cell lymphomas. These patients must be provided the opportunity to be evaluated for this curative approach.

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Fig. 1: Cumulative incidence of NRM in DLBCL/tFL.
Fig. 2: Cumulative incidence of relapse in DLBCL/tFL.
Fig. 3: PFS in DLBCL/tFL.
Fig. 4: OS in DLBCL/tFL.

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Data availability

The datasets generated for this study are available from the corresponding author upon reasonable request and approval by all authors

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Acknowledgements

The authors thank Ms. Zhuo Li, Mayo Clinic, Jacksonville, FL for the statistical support. This work was submitted in part, as an abstract, to the 2024 Annual Meeting of the European Hematology Association in Madrid, Spain.

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Authors and Affiliations

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MAK-D: Designed the study, provided and analyzed the data and prepared the manuscript, RM: Designed the study, provided and analyzed the data and reviewed the manuscript, NE (Easwar): Provided and analyzed the data and reviewed the manuscript, PJ: Provided and analyzed the data and reviewed the manuscript, JY: Provided and analyzed the data and reviewed the manuscript MI: Designed the study, provided and analyzed the data and reviewed the manuscript, NE (Epperla): Provided and analyzed the data and reviewed the manuscript, NA: Provided and analyzed the data and reviewed the manuscript, MH: Provided and analyzed the data and reviewed the manuscript, AB: Provided and analyzed the data and reviewed the manuscript, MN: Provided and analyzed the data and reviewed the manuscript, DJ: Provided and analyzed the data and reviewed the manuscript, PRG: Provided and analyzed the data and reviewed the manuscript, BD: Provided and analyzed the data and reviewed the manuscript, UG: Provided and analyzed the data and reviewed the manuscript, JM: Provided and analyzed the data and reviewed the manuscript, JS-S: Provided and analyzed the data and reviewed the manuscript, FLL: Provided and analyzed the data and reviewed the manuscript, JF: Provided and analyzed the data and reviewed the manuscript, AK: Provided and analyzed the data and reviewed the manuscript, EA: Provided and analyzed the data and reviewed the manuscript, KA: Provided and analyzed the data and reviewed the manuscript, APR: Provided and analyzed the data and reviewed the manuscript, FL: Provided and analyzed the data and reviewed the manuscript, OSA: Provided and analyzed the data and reviewed the manuscript, LL: Provided and analyzed the data and reviewed the manuscript, AM: Provided and analyzed the data and reviewed the manuscript, OOO: Provided and analyzed the data and reviewed the manuscript, JL: Provided and analyzed the data and reviewed the manuscript, MDJ: Provided and analyzed the data and reviewed the manuscript, TS: Provided and analyzed the data and reviewed the manuscript, UD: Provided and analyzed the data and reviewed the manuscript, MAM: Provided and analyzed the data and reviewed the manuscript, JMc: Provided and analyzed the data and reviewed the manuscript, YL: Provided and analyzed the data and reviewed the manuscript, SY: Provided and analyzed the data and reviewed the manuscript, JCC : Designed the study, provided and analyzed the data and prepared the manuscript.

Corresponding author

Correspondence to Julio C. Chavez.

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Competing interests

MAK-D reports grant/research from Bristol Myers Squibb, Novartis and Pharmacyclics, and lecture/honorarium from Kite Pharma; NE (Epperla) reports research funding from Beigene and Eli Lilly. Speakers Bureau for Beigene, Incyte, and Novartis. Ad board for ADC Therapeutics. NA reports Ad Board participation for Bristol Myers Squibb. Consultancy fees for Kite/ Gilead. MH reports research support/Funding: ADC Therapeutics, Spectrum Pharmaceuticals, Astellas Pharma. Consultancy: ADC Therapeutics, Omeros, CRISPR, BMS, Kite, AbbVie, Caribou, Genmab, Autolus. Speaker’s Bureau: ADC Therapeutics, AstraZeneca, Bei Gene, Kite. DMC: Inc, Genentech, Myeloid Therapeutics, CRISPR. PRG reports consultancy services to Kite/Gilead Pharma, Bristol Myers Squibb (BMS) and served on the advisory boards of Pharmacyclics LLC, ADC Therapeutics, Cellectar Biosciences, Ono Pharma, CRISPR therapeutics, IPSEN Biopharma, and Regeneron Pharmaceuticals. AB reports honoraria from Autolus and Kite Pharma. BD reports stocks in Syndax and Iovance Biotherapeutics. Honoraria: MJH Healthcare Holdings, LLC, Curio Science, Gilead Sciences. Consulting/Advisory: Janssen Oncology, Boxer Capital, ADC Therapeutics, Ellipsis, Acrotech Biopharma. Speakers’ Bureau: Gilead Sciences. Research: Pfizer, Poseida therapeutics, MEI Pharma, Angiocrine Bioscience, Takeda, Janssen Oncology, WUGEN, Inc., Orca Bio, Gilead Sciences, AlloVir, Molecular Templates, Atara Biotherapeutics. Travel/accomodations: Poseida. UG reports research/grant support from Bristol Myers Sqibb, Kite Pharma and Novartis. Consultancy/speaker bureau from Kite Pharma. JM reports consulting for Pharmacyclics/Abbvie, Bayer, Gilead/Kite, Beigene, Pfizer, Janssen, Celgene/BMS, Kyowa, Alexion, Fosunkite, Seattle Genetics, Karyopharm, Aurobindo, Verastem, Genmab, Genzyme, Genentech/Roche, ADC Therapeutics, Epizyme, Beigene, Novartis, Morphosys/Incyte, MEI, TG Therapeutics, AstraZeneca, Eli Lilly. Research funding from Bayer, Gilead/Kite, Celgene, Merck, Portola, Incyte, Genentech, Pharmacyclics, Seattle Genetics, Janssen, Millennium, Novartis, Beigene. Honoraria from Targeted Oncology, OncView, Curio, and Physicians’ Education Resource. JS-S reports Speaking for Pfizer (SeaGen) and Ad Board for SeaGen, MassiveBio, ADC therapeutics, Genmab, BeiGene, AbbVie, and Bristol Myers Squibb. FLL reports consulting/advisory role for Allogene, Amgen, bluebird bio, Bristol Myers Squibb, Celgene, Calibr, Cellular Biomedicine Group, Cowen, ecoR1, Emerging Therapy Solutions Gerson Lehman Group, GammaDelta Therapeutics, Iovance, Janssen, Kite, a Gilead Company, Legend Biotech, Novartis, Umoja Biopharma, and Wugen; research funding from Allogene, Kite, and Novartis; and patents, royalties, other intellectual property from several patents held by the institution in my name (unlicensed) in the field of cellular immunotherapy. FL reports advisory board for ADC Therapeutics. OOO reports consultancy and advisory board for Pfizer, Kite, Gilead, AbbVie, Janssen, TGR therapeutics, ADC, Novartis, Epizyme, Curio science, Nektar, Cargo, Caribou. Institution funding from Kite, Pfizer, Daichi Sankyo, Allogene. Honoraria from Pfizer, Gilead. MDJ reports consultancy/advisory for Kite/Gilead, Novartis. Research funding from Kite/Gilead, Incyte, and Loxo@Lilly. TS reports consultancy for BioLine Rx. MAM reports consultancy for AbbVie. JMc reports consulting for Envision, Novartis, Caribou Bio, Sana Technologies, Legend Biotech. Ad Board participation for Autolus, Consulting/Ad Board for Kite/Scimentum, AlloVIr, Bristol Myers Squibb, CRISPR, Nektar. YL reports consulting/advisory board for Janssen, Sanofi, Bristol Myers Squibb, Regeneron, Genentech. Research from Janssen, Bristol Myers Squibb. Scientific Advisory Boards for NexImmune, Caribou. DSMB/EDMC for Pfizer. SY reports consulting for Bristol Myers Squibb and Advisory board for Kite Pharma. JCC Reports advisory/consulting role for Genmab, ADC Therapeutics, Kite/Gilead, Novartis, Astrazeneca, Cellectis, Allogene, BMS, Janssen, Abbvie, Beigene, Pfizer. Research support from Genmab, Merck, Janssen, RM, NE (Easwar), PJ, MI, MN, JF, EA, KA, APR, OSA, LL, JL declare no relevant conflicts of interest to disclose.

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Kharfan-Dabaja, M.A., Mohty, R., Easwar, N. et al. Chimeric antigen receptor T cell therapy in octogenarians with B cell lymphoma: a real-world US multicenter collaborative study. Bone Marrow Transplant 60, 632–639 (2025). https://doi.org/10.1038/s41409-025-02541-1

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