The influence of advanced age on outcomes in patients with diffuse large B-cell lymphoma treated with CAR-T therapy.

Abstract

7034 Background: Chimeric antigen receptor T-Cell (CAR-T) has emerged as a potentially curative treatment for diffuse large B-Cell lymphoma (DLBCL). The median age at DLBCL diagnosis is 66 years with nearly 30% of patients diagnosed at ≥75 years. Studies have examined outcomes of CAR-T therapy in DLBCL, with elderly patients (≥ 65 years) included in analyses; however, clinical trial populations have underrepresented the true age distribution of the disease. This study evaluates the impact of advanced age on survival and toxicity outcomes in patients with DLBCL treated with CAR-T therapy. Methods: A multicenter retrospective cohort study was conducted using TriNetX, a federated database of over 159 million de-identified electronic health record and claims data. Patients aged ≥75 years with DLBCL treated with CD19-directed CAR-T therapy were compared with a 1:1 propensity score–matched cohort of patients aged 18–65. Propensity score matching was performed based on demographics, comorbidities, and baseline laboratory values. Primary outcomes included 1-year and 3-year overall survival (OS), as well as the development of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and infection within 100 days following CAR-T infusion. Outcomes were assessed using Kaplan–Meier survival analyses, hazard ratios (HR), risk ratios (RR), and 95% confidence intervals (CI). Results: Prior to PSM, there were 326 patients ≥ 75 years and 816 patients aged 18-65 years who were treated with CD-19 directed CAR-T for DLBCL. After PSM, there were 241 patients in each cohort. There was no statistically significant difference in one-year or three-year overall survival between patients ≥ 75 years vs. 18-65 years (1-year HR: 0.89, 95% CI [0.63-1.26]; 3-year HR: 1.00, 95% CI [0.74-1.36]). Interestingly, patients ≥ 75 years were at a lower risk for the development of CRS compared younger patients (RR: 0.84, 95% CI [0.72, 0.98]). There was no statistically significant difference in the risk for development of ICANS (RR: 0.98, 95% CI [0.70–1.38]). Risk of infection at 100 days post-CAR-T infusion was lower in patients ≥ 75 years (RR: 0.75, 95% CI [0.58–0.95]). Conclusions: In this large multicenter real-world analysis, patients aged ≥75 years experienced comparable overall survival and no increased toxicity following CAR-T therapy for DLBCL. These findings suggest that advanced age alone should not preclude CAR-T eligibility and support broader consideration of CAR-T therapy in appropriately selected older adults. Outcome Age ≥75 (n=241) Age 18-65 (n=241) HR/RR [95% CI] 1-year OS 71.6% 68.6% 0.89 [0.63-1.26] 3-year OS 47.3% 53.7% 1.00 [0.74-1.36] CRS 52.3% 62.2% 0.84 [0.72–0.98] ICANS 21.6% 22.0% 0.98 [0.70–1.38] Infection (≤100 days) 30.3% 40.7% 0.75 [0.58–0.95]