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Increased Severe Neurotoxicity and Hospital Stay in Octogenarians Receiving CAR T-Cell Therapy for Large B-Cell Lymphoma

Year: 2026

Type: article

Abstract: CD19-targeted CAR T-cell therapy (CAR-T) has transformed treatment for elderly patients with relapsed or refractory large B-cell lymphoma (rrLBCL), yet data on its safety and efficacy in octogenarians (aged ≥80 years) often with more comorbidities and frailty remain limited. In this single-institution retrospective study, 24 octogenarians were identified and matched with 48 patients aged 65-79 years receiving standard-of-care CAR-T using 2:1 propensity score matching. Baseline characteristics were similar, except for more use of lisocabtagene maraleucel and tisagenlecleucel (P<0.001) and bridging therapy (P=0.024) in the octogenarian cohort. Median follow-up was 15.8 and 36.7 months for the octogenarian and comparator cohorts, respectively. The octogenarian cohort had a higher rate of grade ≥3 immune effector cell-associated neurotoxicity syndrome (ICANS) (25% vs 21%; age treatment effect (ATE) P=0.027). Among those experiencing grade ≥3 cytokine release syndrome (CRS) or ICANS, hospital stays were significantly longer in the octogenarian cohort (30 days vs. 16 days, ATE P<0.001). CAR T-cell expansion was reduced in octogenarians, with lower peak counts (ATE P=0.038) and expansion over 28 days post-infusion (ATE P<0.01). Overall and complete response rates were comparable between cohorts. Six- and 12-month progression-free survival rates in octogenarians were 57% and 45%, and overall survival rates were 88% and 81%, respectively, with no significant differences from those of the comparator cohort. These findings suggest that selected octogenarians tolerate and benefit from CAR T-cell therapy and underscore the need for strategies to mitigate severe toxicities through close monitoring and supportive care.

Source: Blood Neoplasia

DOI: 10.1016/j.bneo.2026.100297