CIBMTR Registry Analysis Evaluated the Impact of Age on Outcomes in Patients with LBCL Receiving CAR-T Therapy

Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CD19-directed autologous chimeric antigen receptor T-cell (CAR-T) therapies approved for the treatment of adults with relapsed or refractory large B-cell lymphoma (LBCL). Fewer than 25% of patients in the initial registrational trials (axi-cel, ZUMA-1; tisa-cel, JULIET) were >65 years of age, whereas the median age at diagnosis for LBCL is 66-70 years. Limited data from the registrational trials in managing patients >65 years warrant real-world validation; thus, the Center for International Blood & Marrow Transplant Research (CIBMTR) registry was utilized to study the impact of age on outcomes. Findings were reported at the 64th American Society of Hematology Annual Meeting and Exposition.

CIBMTR registry data were analyzed for clinical data on patients >18 years of age with LBCL who received CAR-T therapy from 2017 to 2020. Age was assessed as a continuous variable and among 3 age groups: <65, 65-74, and ≥75 years. Patient-, disease-, and CAR-T‒related factors were compared across age groups using the chi-square test for categorical variables and the Mann-Whitney U test for continuous variables. Probabilities of overall survival (OS), progression-free survival (PFS), and duration of response were calculated using the Kaplan-Meier estimator, with variance estimated by Greenwood’s formula and comparison across age groups performed using the log-rank test. Multivariate analysis was performed with the Cox proportional hazards model using hazard ratio (HR) and 95% confidence intervals (CIs) for OS, PFS, and progression. Cumulative incidence and severity of cytokine release syndrome (CRS) and immune effectors cell–associated neurotoxicity syndrome (ICANS) were reported as per the consensus American Society for Transplantation and Cellular Therapy criteria and further described with univariate logistic regression analyses.

Of 1916 patients with LBCL identified, 1435 received axi-cel (75%) and 481 received tisa-cel (25%). Overall, the median age at infusion was 63 years (range, 18-91), with 44% of patients ≥65 years, of whom 41% had hematopoietic cell transplantation–specific comorbidity index ≥3. The rate of CRS was 75% (range for all age groups, 78%-69%) and ICANS was 44% (range for all age groups, 37%-49%). The 12-month OS, PFS, and relapse rates were 62% (95% confidence interval [CI], 59-64), 42% (95% CI, 40-45), and 55% (95% CI, 53-57), respectively. In multivariate analyses analyzing the impact of age on outcomes, age as a continuous variable did not impact OS (P = .54), PFS (P = .07), relapse (P = .09), or CRS (P = .87). Increase in age was associated with increase in the incidence of ICANS (HR, 1.03; P <.001). A linear association between age and any-grade ICANS was also demonstrated in patients aged 40-64 years (odds ratio [OR], 1.0; P <.0001) and 65-75 years (OR, 1.65; 95% CI, 1.33-2.05; P <.0001).

While advanced age was not associated with worse PFS, relapse, or CRS, it was significantly associated with higher incidence and grade of ICANS; 64 years was the cutoff point associated with higher risk for ICANS. Advanced age should prompt anticipatory management of neurotoxicity, and comorbidities may impact outcomes after CAR-T therapy. Overall, these data from the CIBMTR registry demonstrate that CAR-T therapy is feasible for older adults and not associated with worse survival outcomes.

Source

Mirza A, Hosing C, Foss FM, et al. Impact of age on outcomes after CD19 directed CAR T cell therapy for large B cell lymphomas: real world experience from the Center for International Blood & Marrow Transplant Research (CIBMTR). Presented at: 64th American Society of Hematology Annual Meeting and Exposition, December 10-13, 2022; New Orleans, LA. Poster presentation 2024.