Toxicity and Efficacy of CAR T-cell Therapy in PCNSL and SCNSL: A Meta-Analysis of 128 Patients.

Relapsed/refractory primary and secondary central nervous system lymphomas (PCNSL, SCNSL) are associated with short survival and represent an unmet need, requiring novel effective strategies. Anti-CD19 CAR T-cells, effective in systemic large B-cell lymphoma (LBCL), have shown responses in PCNSL and SCNSL in early reports, but with limited sample size. We therefore performed a comprehensive systematic review and meta-analysis of all published data describing CAR T-cell use in PCNSL and SCNSL. This identified 128 patients with PCNSL (30) and SCNSL (98). Our primary objectives were to evaluate CAR T-cell specific toxicity (ICANS and CRS) as well as response rates in these two populations. 70% of patients with PCNSL had CRS of any grade (13% grade 3-4) and 53% had ICANS of any grade (18% grade 3-4). Comparatively, 72% of the SCNSL cohort experienced CRS of any grade (11% grade 3-4) and 48% had ICANS of any grade (26% grade 3-4). Of the PCNSL patients, 56% achieved a CR with 37% remaining in remission at 6 months. Similarly, 47% of SCNSL patients had a CR, with 37% in remission at 6 months. In a large meta-analysis of CNS lymphomas, toxicity of anti-CD19 CAR T-cell therapy was similar to that of registrational studies in systemic LBCL with no increased signal of neurotoxicity observed. Encouraging efficacy was demonstrated in patients with CNS lymphoma with no discernible differences between PCNSL and SCNSL.