Impact of age on outcomes of CAR-T cell therapy in multiple myeloma, DLBCL, and follicular lymphoma: A real-world multi-center propensity-matched analysis

Abstract Background Chimeric antigen receptor T-cell (CAR-T) therapy has transformed the management of relapsed and refractory hematologic malignancies. However, real-world data regarding its efficacy and safety in elderly patients remains less well-characterized and underrepresented in clinical trials due to presumed higher risks of toxicity, hospitalization, and other side effects. This study aimed to compare the outcomes of CAR-T therapy in adults aged 18–75 years versus those >75 years across multiple myeloma, follicular lymphoma, and diffuse large B-cell lymphoma patients using a multi-center, federated health research network. Methods: A retrospective cohort analysis was conducted using the TriNetX Research Network, comprising data from 105 healthcare organizations. Adults diagnosed with multiple myeloma, diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma (FL) who received CAR-T therapy were identified and included using corresponding ICD-10 codes. Patients were stratified into two cohorts based on age at the time of CAR-T infusion: 18–75 years (n=3,229) and >75 years (n=525). Propensity score matching (1:1) was applied to control for confounding, yielding 112 patients per cohort. Outcomes assessed included overall survival (OS), ICU admissions, Serious adverse events (cytokine release syndrome (CRS)/immune effector cell-associated neurotoxicity syndrome (ICANS)), and the development of cytopenia. Kaplan-Meier survival analysis, risk differences, and risk ratios were performed. Results: Following 1:1 propensity score matching, each cohort included 112 patients. The baseline characteristics were well-balanced between age groups. Among patients aged 18–75 and those >75 years, males represented 60.7% and 58.0%, respectively. The majority of patients in both groups identified as White (77.7%), followed by Black or African American (8.9%), and Asian (8.9%); 80.4% of the cohorts were identified as non-Hispanic. At the end of the follow-up, overall survival was 54.4% in the (18–75) group versus 49.0% in the (>75) group (p=0.456). ICU admissions were slightly higher among older patients but were not statistically significant (18.8% vs. 14.3%, p=0.368). Additionally, CRS/ICANS (23.2% vs. 25.9%, p=0.641) and Cytopenia incidence (60.9% vs. 59.3%, p=0.855) were similar between the two cohorts (18-75 years Vs >75 years), respectively. Conclusion: In this large, real-world study of CAR-T therapy among multiple myeloma, DLBCL, and follicular lymphoma patients, older adults (>75) experienced comparable survival, disease control, and toxicity outcomes relative to their younger counterparts (18-75 years old). These findings suggest that chronological age alone should not be solely used as an inclusion criterion for CAR-T therapy and support its consideration in appropriately selected elderly patients.