Impact of age on outcomes after CD19 CAR T-cell therapy for large B-cell lymphomas

Abstract

Age may influence clinical outcomes after CD19-directed chimeric antigen receptor (CAR) T-cell (CAR-T) therapy. Real-world data on the survival and toxicity outcomes of older patients receiving CAR-T therapy are limited. We used data from the Center for International Blood and Marrow Transplant Research for adults with diffuse large B-cell lymphoma who received CAR-T therapy from May 2018 to June 2020. Cumulative incidence and severity of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) were reported. Efficacy and safety outcomes were assessed using age as a continuous variable and among 4 age groups: 18 to 54, 55 to 64, 65 to 74, and ≥75 years. Nearly half (44%) of 1916 total recipients were aged ≥65 years. Patients received either axicabtagene ciloleucel (75%) or tisagenlecleucel (25%). Overall rates of CRS and ICANS were 75% and 43%, and severe rates of CRS and ICANS were 9% and 21%, respectively. For all patients, 12-month overall survival (OS), progression-free survival (PFS), and relapse rates were 62%, 42%, and 55%, respectively. As a continuous variable, older age did not affect OS, PFS, and CRS; however, the risk of ICANS increased with age (hazard ratio [HR], 1.03; P < .001). At age >64 years, risk for ICANS increases (HR, 1.65;95% confidence interval (CI), 1.33-2.1; P < .001). In a categorical analysis, the 65 to 74-year age group had lower relapse risk (HR, 0.77;95% CI, 0.64-0.93; P = .005) than younger patients. CD19 CAR-T therapy is effective for older adults, and older age does not worsen mortality. Older age is associated with higher ICANS risk and should guide patient selection.