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

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.