Background: Tisagenlecleucel is an autologous CD19-directed chimeric antigen receptor (CAR)-T cell therapy approved for the treatment of patients (pts) with relapsed/refractory (r/r) large B-cell lymphoma (LBCL) who have received ≥2 lines of prior therapy. Previous analysis of the Center for International Blood & Marrow Transplant Research (CIBMTR) registry showed high rates of durable response with progression-free survival (PFS), duration of response, and overall survival (OS) rates at 24 mo of 28%, 53%, and 44%, respectively, as well as similar efficacy outcomes among pts age ≥65 y as compared with pts age <65 y (Landsburg et al, ASH 2022). Although it has been shown that real-world pts treated with CAR-T cell therapy are older than those included in pivotal trials, limited data on CAR-T outcomes among pts age ≥75 y are available. Here, we report the first analysis of clinical outcomes in pts age ≥75 y with r/r LBCL treated with tisagenlecleucel in the real-world setting.

Methods: Data were collected as a part of a noninterventional, prospective, longitudinal study using the CIBMTR cellular therapy registry. All pts were treated in the United States, Canada, or Israel. Efficacy outcomes analyzed included overall response rate (ORR), complete response rate (CRR), PFS, and OS. Key safety outcomes included the incidence and severity of adverse events, cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). Nominal P values are reported without adjusting for multiplicity.

Results: As of May 4, 2023, 1375 pts had received tisagenlecleucel (infused set); 278 pts were age ≥75 y. Pts age ≥75 y had similar baseline characteristics compared with pts age <75 y (Eastern Cooperative Oncology Group 0-1, 85% in both populations; elevated lactate dehydrogenase [LDH], 47% in both populations), received similar lymphodepleting regimens, and received tisagenlecleucel in a similar number of days post relapse (81 d vs 85 d, respectively). Pts age ≥75 y had a lower frequency of prior autologous hematopoietic cell transplantation than pts age <75 y (12% vs 26%, respectively) (Figure). One hundred twenty-one pts age ≥75 y had comorbidities (121/278, 44%), including pulmonary disease (65/278, 23%), cardiac disease (60/278, 22%), and hepatic disease (21/278, 8%). Among 247 pts age ≥75 y who were evaluated for efficacy, the ORR (CR + partial response) was 64% (95% CI, 58.1-70.3) and CRR was 47% (95% CI, 41.0-53.8). ORR was similar in pts age <75 y (n=984; 60% [95% CI, 56.9-63.1]), as was CRR (46% [95% CI, 43.2-49.5]). With a median length of follow-up (infusion to data cutoff) of 30 mo, 24-mo PFS in pts age ≥75 y was 23% (95% CI, 16.7-30.1) compared with 28% in pts age <75 y (95% CI, 25.1-31.7). Twenty-four-mo OS in pts age ≥75 y was 39% (95% CI, 31.2-47.2) compared with 44% (95% CI, 40.1-47.8) in pts age <75 y (Figure).

AE frequency in pts age ≥75 y (n=250) was comparable with pts age <75 y (n=1004), including the incidence of all-grade CRS (57% vs 60%, respectively; P=0.31) and grade 3/4 CRS (6% of each subgroup). Grade 5 CRS occurred in 2 pts age ≥75 y and 6 pts age <75 y. Tocilizumab was used to manage CRS in 66% of pts age ≥75 y compared with 56% of pts age <75. All-grade ICANS frequency in pts age ≥75 y was comparable with pts age <75 y (27% vs 22%, respectively; P=0.06). Grade 3/4 ICANS was experienced by 7% of each subgroup. Four pts age ≥75 y experienced grade 5 ICANS compared with 1 pt age <75 y. Median time to ICANS onset was similar in pts age ≥75 y (5 d, range 2.0-6.5) and pts age <75 y (5 d, range 3.0-8.0). Corticosteroids were used with similar frequency to manage ICANS in pts age ≥75 y (68%) compared with pts age <75 y (65%).

Conclusions: In the first analysis of pts age ≥75 y, tisagenlecleucel demonstrated similar efficacy and rates of CRS and ICANS in pts with r/r LBCL age ≥75 y as compared with age <75 y. As few pts with r/r LBCL age ≥75 y received CAR-T cell therapy in clinical trials, real-world evidence for this age group is invaluable for guiding treatment decisions in this clinical setting, and supports consideration of tisagenlecleucel, a therapy that results in durable disease control in approximately one quarter of patients with a low risk of severe toxicity.

Landsburg:Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Travel funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Curis: Research Funding; Calithera: Membership on an entity's Board of Directors or advisory committees, Research Funding; Epizyme: Membership on an entity's Board of Directors or advisory committees; ADCT: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Morphosys: Membership on an entity's Board of Directors or advisory committees. Foley:Janssen: Speakers Bureau; Novartis: Speakers Bureau; Gilead: Speakers Bureau. Hill:Kite, a Gilead Company: Consultancy, Honoraria, Other: travel support, Research Funding; Pharmacyclics: Consultancy, Other: Advisory board, Research Funding; Genentech: Consultancy, Other: Advisory board, Research Funding; Bristol Myers Squibb: Consultancy; BeiGene: Consultancy; AstraZeneca: Consultancy; AbbVie: Consultancy, Other: Advisory board, Research Funding; Incyte: Consultancy; Gilead: Other: Advisory board. Jacobson:Synthekine: Consultancy, Honoraria; Abbvie: Consultancy; Abintus Bio: Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Consultancy; AstraZeneca: Consultancy; BMS/Celgene: Consultancy; Caribou Bio: Consultancy; Daiichi-Sankyo: Consultancy; ImmPACT Bio: Consultancy; Instil Bio: Consultancy; Ipsen: Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Consultancy, Honoraria, Research Funding; Morphosys: Consultancy; Novartis: Consultancy; Sana: Consultancy, Honoraria. Jaglowski:CRISPR: Consultancy; Takeda: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Kite. a Gilead Company: Consultancy, Research Funding; Caribou: Research Funding. Locke:Clinical Care Options Oncology: Other; Calibr: Consultancy; ASH: Other: Travel Support; Kite, a Gilead Company: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Institutional , Research Funding; GammaDelta Therapeutics: Consultancy; Bluebird Bio: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Institutional; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Society for Immunotherapy of Cancer: Other; Leukemia and Lymphoma Society: Other; National Cancer Institute: Other; BioPharma Communications CARE Education: Other: Institutional; Caribou: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Allogene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Institutional ; Wugen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sana: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Umoja: Consultancy, Membership on an entity's Board of Directors or advisory committees; Cellular Medicine Group: Consultancy; Cowen: Consultancy; Aptitude Health: Other: Travel Support; Iovance: Consultancy, Membership on an entity's Board of Directors or advisory committees; CERo Therapeutics: Other: (Institutional); Imedex: Other; EcoR1: Consultancy; Emerging Therapy Solutions: Consultancy, Other; Legend Biotech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Institutional , Research Funding; Bristol Myers Squibb/ Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Institutional , Research Funding; Daiichi Sankyo: Consultancy; Gerson Lehrman Group (GLG): Consultancy; A2 Biotherapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel support. Ram:MSD: Honoraria; Novartis: Honoraria, Research Funding; Gilead: Honoraria; BMS, Takeda, Sanofi, Pfizer: Honoraria. Riedell:Novartis: Honoraria; AbbVie, Genmab, ADC Therapeutics, Pharmacyclics, Novartis, BMS, Kite/Gilead, Nurix Therapeutics, Nektar Therapeutics, Takeda, Intellia Therapeutics, Sana Biotechnology, BeiGene, Janssen, CVS Caremark: Consultancy; Kite/Gilead: Speakers Bureau; BMS, Kite/Gilead, Novartis, MorphoSys, CRISPR Therapeutics, Calibr, Xencor, Fate Therapeutics, Tessa Therapeutics.: Research Funding. Popplewell:La Roche: Honoraria; Hoffmann: Honoraria; Seattle Genetics: Consultancy, Honoraria; Novartis: Consultancy; Pfizer: Honoraria. Tiwari:Novartis Healthcare Private Limited: Current Employment. Lim:Novartis: Current Employment, Current equity holder in publicly-traded company. Maier:Novartis Pharma AG: Current Employment. Majdan:Novartis: Current Employment. Pasquini:Novartis: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Kite, a Gilead Company: Honoraria, Research Funding; Janssen: Research Funding; Kite Brazil: Honoraria. Frigault:Arcellx: Consultancy, Research Funding; BMS: Consultancy; Iovance: Consultancy; Kite: Consultancy, Research Funding; Novartis: Consultancy, Research Funding.

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2023
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