denotes an abstract that is clinically relevant.
denotes that this is a recommended PHD Trainee Session.
denotes that this is a ticketed session.Session: 705. Cellular Immunotherapies: Late Phase and Commercially Available Therapies: Poster II
Hematology Disease Topics & Pathways:
adult, Biological therapies, elderly, Lymphomas, non-Hodgkin lymphoma, Chimeric Antigen Receptor (CAR)-T Cell Therapies, B Cell lymphoma, Diseases, Therapies, Lymphoid Malignancies, Human, Study Population
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.
Disclosures: 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: Kite, a Gilead company: Consultancy, Honoraria, Research Funding; Synthekine: Consultancy, Honoraria; Morphosys: Consultancy; Ipsen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Daiichi-Sankyo: Consultancy, Honoraria; ImmPACT Bio: Consultancy, Honoraria; Instil Bio: Consultancy, Honoraria; Caribou Bio: Consultancy; Abintus Bio: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy; ADC Therapeutics: Consultancy; Abbvie: Consultancy, Honoraria; Bristol Myers Squibb/Celgene: Consultancy; Novartis: Consultancy, Honoraria, Other: Travel support; Pfizer: Research Funding; Miltenyi Biotec: Consultancy; Sana: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Other: Travel support; Lonza: Consultancy, Honoraria, Other: Travel support; Epizyme: Consultancy, Honoraria; Bluebird Bio: Consultancy, Honoraria; Humanigen: Consultancy, Honoraria, Other: Travel support; Nkarta: Consultancy, Honoraria; Precision BioSciences: Consultancy, Honoraria, Other: Travel support; Clinical Care Options: Speakers Bureau; Axis: Speakers Bureau. 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.