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3752 Comparative Real-World Outcomes of Commercial CD19-Directed CAR T-Cell Therapies in Large B-Cell Lymphoma

Program: Oral and Poster Abstracts
Session: 906. Outcomes Research: Lymphoid Malignancies Excluding Plasma Cell Disorders: Poster II
Hematology Disease Topics & Pathways:
Research, Lymphomas, Non-Hodgkin lymphoma, Clinical Research, Health outcomes research, B Cell lymphoma, Diseases, Real-world evidence, Aggressive lymphoma, Lymphoid Malignancies
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Xavier Deschênes-Simard, MD, PhD1,2,3*, Maria Bromberg, MPH4*, Sean M. Devlin, PhD4*, Ofrat Beyar Katz5,6, Andrew Ip, MD, MSc7,8, Ronit Marcus, MD9,10*, Abraham Avigdor, MD10,11, Annamaria Ballweg, MD12*, Emma Rabinovich, MD13,14, Mohammad Alhomoud, MD15, Alfredo Rivas-Delgado, MD, PhD16, Magdalena Corona, MD, PhD3*, Alejandro Luna De Abia, MD, PhD15,17*, Maria Lia Palomba, MD18,19, Gunjan L. Shah, MD20,21,22, Richard J. Lin, MD, PhD20,21,22, Alexander P. Boardman, MD16,21,22*, Lorenzo Falchi, MD18,21,22, Jennifer Kimberly Lue, MD18,22, Gilles Salles, MD, PhD18,19,21, Miguel-Angel Perales, MD20,21,23, Roni Shouval, MD, PhD15,21,23, Parastoo B Dahi, MD20,21,22* and Michael Scordo, MD21,22,24

1Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY
2Department of Medicine, University of Montreal, Montréal, QC, Canada
3Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY
4Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY
5Department of Hematology and BMT, Rambam Health Care Campus, Haifa, Israel
6The Ruth and Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel
7Hackensack Meridian School of Medicine, Hackensack, NJ
8Lymphoma Division, John Theurer Cancer Center, Hackensack Meridian Health, Hackensack, NJ
9School of Medicine, Faculty of Medical and health Sciences,Aviv University, Tel Aviv, Israel
10Division of Hematology & Bone marrow transplantation, Chaim Sheba Medical Center, Tel-Hashomer, Israel, School of Medicine, Tel-Aviv University, Tel Aviv, Israel
11School of Medicine, Faculty of Medical and health Sciences, Aviv University, Tel Aviv, Israel
12Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York
13Department of Bone Marrow Transplant, Memorial Sloan Kettering Cancer Center, New York, NY
14Rutgers Cancer Institute, Robert Wood Johnson Barnabas, New Brunswick, NJ
15Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
16Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY
17Unidad de trasplante y terapia celular, Hospital Universitario Ramon y Cajal, Madrid, Spain
18Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
19Department of Medicine, Weill Cornell Medical College, New York
20Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
21Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
22Department of Medicine, Weill Cornell Medical College, New York, NY
23Department of Medicine, Weill Cornell Medicine, New York, NY
24Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, NY

Introduction: Although the US FDA has approved 3 commercial CAR T-cell therapies for large B-cell lymphoma (LBCL), there are no randomized clinical trials directly comparing their efficacy and safety. Recent studies have supported the higher efficacy, but higher toxicity, of axicabtagene ciloleucel (axi-cel) compared to tisagenlecleucel (tisa-cel). However, there is no such comparison with lisocabtagene maraleucel (liso-cel). Here, we compare the real-world clinical outcomes of patients treated for LBCL with the 3 commercially available CAR T-cell products.

Methods: We conducted a retrospective multicenter cohort study involving 501 patients from 4 centers in the USA and Israel, treated for LBCL between April 2016 and January 2024. We included only patients treated with commercially available CAR T-cells outside of prospective clinical trials. Patient characteristics between the cohorts were compared using Pearson’s Chi-squared test, Fisher’s exact test, or Kruskal-Wallis rank sum test. Multivariable analyses using Cox proportional hazards models were conducted to adjust for age, performance status, LBCL subtype, refractory vs. relapse status, stage at apheresis, bridging therapy, disease response pre-infusion, LDH, and line of treatment.

Results: Among all patients, 96 (19%), 133 (27%), and 272 (54%) received liso-cel, tisa-cel, and axi-cel, respectively. Patients who received liso-cel and tisa-cel were older compared to those treated with axi-cel (median ages: 70, 71, 62 years, respectively; p˂0.001) and had a poorer performance status at cell infusion (KPS˂90 in 75%, 59%, 56%, respectively; p=0.004). Patients treated with liso-cel and tisa-cel had less aggressive disease biology compared to those treated with axi-cel, respectively: refractory disease pre-apheresis (35%, 33%, 49%; p=0.002) and bulky disease pre-apheresis (12%, 10%, 21%; p=0.013). Most patients received tisa-cel in the ≥ 3rd line of treatment (liso-cel 78%, tisa-cel 96%, and axi-cel 81%; p<0.001). The time from apheresis to cell infusion was longer with liso-cel and tisa-cel compared to axi-cel (41, 44, 35 days, respectively; p˂0.001). Other baseline characteristics, including use of bridging therapy and LDH pre-lymphodepletion, were similar.

The median follow-up among patients in the cohort was 19 months. The objective response (OR) rate with liso-cel was higher than with tisa-cel and axi-cel (91%, 66%, 82%, respectively; p<0.001), and a higher percentage reached complete remission (CR) (75%, 53%, 68%, respectively; p=0.001). The median duration of CR was not reached for liso cell but was 18 months (95% CI: 7.4-NR months) for tisa-cel and 27 months (95% CI: 19-NR months) for axi-cel. After adjusting for baseline clinical covariates, there was no significant difference in progression-free survival (PFS) between liso-cel and axi-cel (HR 0.87; p=0.5) in the multivariable model but tisa-cel was associated with inferior PFS compared to axi-cel (HR 2.0; p<0.001) and liso-cel (HR 2.31; p<0.001); 2-year estimated PFS was 52% (95% CI: 39-70%) for liso-cel, 27% (95% CI: 20-37%) for tisa-cel, and 44% (95% CI: 37-52%) for axi-cel. There were no statistically significant differences in overall survival (OS) between the 3 products after adjusting for clinical covariates; 2-year estimated OS was 52% (95% CI: 39-70%) for liso-cel, 44% (95% CI: 35-54%) for tisa-cel, and 60% (95% CI: 53-67%) for axi-cel.

Lower rates of any-grade CRS were observed with liso-cel compared to tisa-cel and axi-cel (54%, 71%, and 89%, respectively; p<0.001). Additionally, liso-cel was associated with less high-grade CRS (grade ≥2: liso-cel 16%, tisa-cel 33%, axi-cel 43%; p<0.001), any-grade ICANS (liso-cel 17%, tisa-cel 18%, axi-cel 38%; p<0.001), and high-grade ICANS (grade ≥2: liso-cel 10%, tisa-cel 9.8%, axi-cel 25%; p<0.001).

Conclusion: In this real-world comparison, we observed that tisa-cel was associated with inferior efficacy compared to axi-cel and liso-cel. While OR and CR rates were higher in patients receiving liso-cel versus axi-cel, PFS and OS rates were similar. Additionally, liso-cel demonstrated the most favorable toxicity profile. These findings provide valuable insights into product selection and suggest that liso-cel, often preferred for older and frail patients, could also be considered for younger and fitter patients.

Disclosures: Avigdor: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau; BeiGene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Speakers Bureau; Ascentage: Consultancy, Honoraria, Speakers Bureau; Karyospharm: Research Funding; TG Therapeutics: Consultancy; Eli Lilly: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau. Palomba: Cellectar: Consultancy; Synthekine: Consultancy; Novartis: Consultancy; Bristo Meyer Squibb: Consultancy, Patents & Royalties: immediate family member. Shah: Janssen, Amgen, Beyond Spring, BMS, GPCR, DSMB with ArcellX.: Research Funding. Boardman: OncLive: Honoraria; Bristol Myers Squibb: Consultancy; Cancer Study Group, LLC: Consultancy. Falchi: Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; EvolveImmune: Consultancy; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genmab: Consultancy, Research Funding; Roche: Consultancy, Research Funding; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Memorial Sloan Kettering Cancer Center: Current Employment; Genentech, Roche, Genmab, AbbVie, Innate, BeiGene: Research Funding; Genentech, Roche, Genmab, Abbvie, Sanofi, EvolveImmune: Honoraria; AbbVie, Genentech, ADC Therapeutics, Seagen, Ipsen: Membership on an entity's Board of Directors or advisory committees; Taylor Francis: Other: Journal Editor; Kaplan: Other: CME Presentation: Projects in Knowledge. Lue: ADC Therapeutics: Consultancy; GenMab: Consultancy; Merck Pharmaceuticals: Consultancy; Kymera Therapeutics: Research Funding; Lumanity: Consultancy. Salles: BeiGene: Consultancy; BMS/Celgene: Consultancy; Ipsen: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Merck: Consultancy; Kite/Gilead: Consultancy; AbbVie: Consultancy, Research Funding; Genmab: Consultancy, Research Funding; Incyte: Consultancy; Genentech/Roche: Consultancy, Research Funding; Molecular Partners: Consultancy; Nurix: Research Funding. Perales: Nektar: Research Funding; Novartis: Research Funding; Biotec: Research Funding; Miltenyi: Research Funding; Kite/Gilead: Research Funding; Incyte: Research Funding; Allogene: Research Funding; OrcaBio: Current equity holder in private company; Omeros: Current Employment, Current equity holder in publicly-traded company; NexImmune: Current Employment, Current equity holder in publicly-traded company. Scordo: Amgen: Research Funding; Angiocrine Biosciences, Inc.: Research Funding; Medscape: Honoraria; Miltenyi Biotec: Consultancy; IDEOlogy: Honoraria; Sanofi: Research Funding; MJH Life Sciences (Cancer Network): Honoraria; Kite - A Gilead Company: Consultancy; Omeros Corporation: Consultancy, Research Funding.

*signifies non-member of ASH