Neurotoxicity in Older Patients with Relapsed or Refractory Large B-Cell Lymphoma Treated with Chimeric Antigen Receptor T-Cell Therapy: A Multicenter Study

Anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy is a standard treatment option in relapsed or refractory (RR) large B-cell lymphoma (LBCL), including older patients. However, immune effector cell-associated neurotoxicity syndrome (ICANS)/neurotoxicity is frequent and can be debilitating, especially in older patients, and incidence and risk factors are not well defined in such patients. This retrospective multicenter study included older patients (≥65 yr) with RR LBCL treated with commercial CAR-T therapy between December 2017 and April 2023. The primary study outcome included 30-d cumulative estimates of ICANS, using deaths/progressions as competing risks. A total of 224 patients were included; among them, 131 (58%) received axicabtagene ciloleucel, 36 (16%) were treated with tisagenlecleucel, and 57 (25%) had lisocabtagene maraleucel. The median age at CAR-T therapy was 71 yr (range 65 to 89), and 26 (12%) were ≥80 yr old. The 30-d estimates for all grades and grades ≥3 ICANS were 50.9% (95% CI 44.7 to 57.9) and 29.8% (95% CI 24.0 to 37.0), respectively. Age at CAR-T therapy did not impact incidence, onset, and duration of ICANS. In contrast, ECOG PS scale of ≥2, an elevated lactate dehydrogenase level, and the use of axicabtagene ciloleucel were associated with a higher incidence of grade ≥3 ICANS. Age at CAR-T therapy did not impact the risks of ICANS in older patients with RR LBCL. Comprehensive neurocognitive and frailty assessments and appropriate candidate selections are crucial.