Impact of Age on Outcomes after CD19 CAR-T Cell Therapy for Large B-Cell Lymphomas Open Access

• Older adults have similar cytokine release syndrome and survival, compared to younger patients. However, neurotoxicity increases with age

• Advanced age is not a barrier to receiving CD19 chimeric antigen receptor T cells, but research is needed to reduce neurotoxicity

Age may influence clinical outcomes after CD19-directed chimeric antigen receptor T cell (CAR-T) therapy. Real-world data on the survival and toxicity outcomes of older patients receiving CAR T-cell therapy are limited. We used data from Center for International Blood and Marrow Transplant Research (CIBMTR) for adults with diffuse large B-cell lymphoma who received a CAR-T 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 amongst four age groups: 18-54, 55-64, 65-74, and ≥75 years. Nearly half (44%) of 1916 total recipients were aged 65 or older. 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 OS, PFS, and relapse rates were 62%, 42%, 55%, respectively. As a continuous variable, older age did not affect OS, PFS and CRS. Risk of ICANS increased with age (hazard ratio [HR], 1.03; P < .001). Beyond age 64, risk for ICANS increases (HR, 1.65; 95% CI, 1.33-2.1; P < .001). In a categorical analysis, the 65-74 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.