What question did this study set out to answer?

This study investigates the incidence of immune effector cell-associated neurotoxicity syndrome (ICANS) in older patients with relapsed or refractory large B-cell lymphoma treated with CAR-T therapy.

April 4, 2026Open Access

Neurotoxicity in older patients with relapsed or refractory large B-cell lymphoma treated with CAR T-cell therapy: A multicenter study

Key Points

This study investigates the incidence of immune effector cell-associated neurotoxicity syndrome (ICANS) in older patients with relapsed or refractory large B-cell lymphoma treated with CAR-T therapy.
Retrospective multicenter analysis of older patients (≥65 years) with relapsed or refractory large B-cell lymphoma
Assessment of cumulative estimates of ICANS within 30 days using competing risks for deaths/progressions
Evaluation of risk factors including ECOG performance status and LDH levels
In the study, 224 older patients were analyzed, with a median age of 71 years.
30-day estimates indicated 50.9% incidence of all grade ICANS and 29.8% for grade ≥3 ICANS.
Elevated LDH and poor performance status were associated with higher risks of grade ≥3 ICANS.

Abstract

• Age at CAR-T therapy did not influence the risks of ICANS in older patients with RR LBCL. • Frail patients with a poor performance status and an elevated LDH level have an increased risk of grade ≥3 ICANS. • Comprehensive neurocognitive, geriatric, and frailty assessments, along with the selection of appropriate candidates, are crucial for older patients undergoing CAR-T therapy. Purpose: 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. Methods: This retrospective multicenter study included older patients (≥65 years) with RR LBCL treated with commercial CAR-T therapy between December 2017 and April 2023. The primary study outcome included 30-day cumulative estimates of ICANS, using deaths/progressions as competing risks. Results: 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 years (range 65–89), and 26 (12%) were ≥80 years old. The 30-day estimates for all grade and grade ≥3 ICANS were 50.9% (95% CI 44.7–57.9) and 29.8% (95% CI 24.0–37.0), respectively. Age at CAR-T therapy did not impact incidence, onset, and duration of ICANS. In contrast, ECOG PS scale of ≥2, an elevated LDH level, and the use of axicabtagene ciloleucel were associated with a higher incidence of grade ≥3 ICANS. Conclusions : 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.

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Cite This Study

Tun et al. (Wed,) studied this question.

synapsesocial.com/papers/69d0af52659487ece0fa52f9 https://doi.org/https://doi.org/10.1016/j.jtct.2026.03.041

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