Real-world outcomes of axicabtagene ciloleucel in older versus younger adults with diffuse large B-cell lymphoma.

Abstract

e19102 Background: Axicabtagene ciloleucel (axi-cel) has substantially improved outcomes for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). However, older adults are underrepresented in pivotal clinical trials, and real-world data describing long-term survival and treatment-related toxicity in patients aged 70 years and older remain limited. Methods: We performed a retrospective cohort study using the TriNetX Global Collaborative Network to evaluate adult patients with DLBCL treated with axi-cel. Patients were stratified by age at the time of CAR-T infusion (<70 vs ≥70 years). The primary outcome was all-cause mortality at 3 years. Secondary outcomes included acute respiratory failure (ARF) at 30 days and 1 year as a surrogate for severe treatment-related toxicity. Survival outcomes were assessed using Kaplan–Meier analysis, risk estimates, and Cox proportional hazards models. Propensity score matching was explored but was not feasible due to limited overlap in baseline characteristics between age groups. Results: A total of 818 patients treated with axi-cel were identified across 23 healthcare organizations, including 517 patients aged <70 years and 301 patients aged ≥70 years. At 3 years, mortality was significantly higher among patients aged ≥70 compared with those aged <70 (43.0% vs 33.1%; risk ratio [RR] 0.77, 95% CI 0.64–0.92; p=0.0046). Correspondingly, 3-year overall survival was lower in the older cohort (49.9% vs 60.7%; log-rank p=0.0236). On multivariable Cox regression, age <70 years was independently associated with improved overall survival (hazard ratio [HR] 0.77, 95% CI 0.61–0.97). Rates of acute respiratory failure were low and did not differ significantly between age groups. At 30 days, ARF occurred in 5.7% of patients aged <70 years and 6.2% of patients aged ≥70 years (HR 0.95, 95% CI 0.50–1.80; p=0.87). Similar results were observed at 1 year, with no significant age-based differences. Conclusions: In this large real-world analysis, older adults receiving axi-cel for DLBCL experienced significantly worse long-term survival compared with younger patients, while early severe respiratory toxicity was comparable between age groups. These findings support the feasibility of CAR-T therapy in carefully selected older adults but underscore the need for improved long-term outcomes and age-specific risk stratification strategies in this growing patient population.