Outcomes of CD19 CAR‐T therapy in central nervous system lymphoma: Insights from a multicentre experience

Summary Chimeric antigen receptor (CAR) T‐cell therapy has reshaped the treatment paradigm for relapsed/refractory (R/R) diffuse large B‐cell lymphoma (DLBCL). However, its role in central nervous system lymphoma (CNSL) remains uncertain. We conducted a multicentre, retrospective study on 54 adult R/R CNSL patients treated at four international institutions with commercial (axi‐cel, tisa‐cel, liso‐cel) or a point of care (POC) CD19‐CAR T‐cell products. At day 100 post CAR‐T infusion, 65% of patients attained a complete response as their best response in both systemic and central nervous system compartments. The median progression‐free survival (PFS) was 7.5 months, with a 1‐year PFS of 35%. The median overall survival (OS) was 19 months, with a 1‐year OS of 63%. In multivariable analyses, CAR‐T product was significantly associated with PFS ( p = 0.009) and OS ( p = 0.013), with patients receiving tisa‐cel exhibiting poorer outcomes than axi‐cel and patients receiving liso‐cel or POC CAR‐T product demonstrating better outcomes than axi‐cel. Toxicity profiles were consistent with pivotal trials in R/R DLBCL. Grade ≥3 cytokine release syndrome occurred in 11% of patients, while grade ≥3 immune‐effector cell‐associated neurotoxicity syndrome was observed in 28%. Our study supports the feasibility and safety of anti‐CD19 CAR‐T therapy in CNSL. The specific CAR‐T product infused emerged as a factor influencing outcomes.