CD8 and CD4 CAR-T cells are associated with outcome and toxicity of tisagenlecleucel in central nervous system lymphoma.

Samara, Jules Al; Baron, Marine; Gazzano, Marianne; Parizot, Christophe; Kirupaharan, Mathiiz; Guihot, Amélie; Miyara, Makoto; Gorochov, Guy et al. · Cytotherapy · 2025

retrospective_cohort · Level III

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Abstract

CAR-T cells have been proposed as a new treatment option for primary and secondary central nervous system lymphoma (CNSL). However, whether CAR-T cell features contribute to response and toxicity in CNSL remains elusive. Twenty-four patients with primary and secondary CNSL treated with tisagenlecleucel were retrospectively included in this study. CAR-T cells were analysed in infusion products, blood ans cerebrospinal fluid using flow cytometry. Here, we show that robust expansion of CD8<sup>+</sup> CAR-T cells was associated with early response and better long-term survival. Additionally, CD4<sup>+</sup> CAR-T cells appeared to play a pivotal role in the development of cytokine release syndrome. These data represent the first evidence of these mechanisms in CNSL patients and emphasize the relevance of CAR-T cell phenotype monitoring to predict efficacy and toxicity.

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