A meta-analysis of anti-CD19-chimeric antigen receptor (CAR) T-cell therapy published in Blood Advances showed promising complete response (CR) rates among patients with central nervous system lymphoma (CNSL). Neurotoxicity rates also appeared to be similar to those seen in registrational trials of systemic large B-cell lymphoma (LBCL).

In recent years, CAR-T therapy has shown promise in the LBCL setting, and several drugs have received regulatory approval in the United States.

Primary and secondary CNSL (PCNSL and SCNSL, respectively) remain, however, areas of unmet clinical need. This is especially true given that previous research suggests that patients with CNSL are at an increased risk of immune effector cell-associated neurotoxicity syndrome (ICANS) — a potentially serious adverse event linked with this novel set of treatments.

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Furthermore, there are few available data of CR and ICANS rates among patients with PCNSL and SCNSL treated with CAR-T therapy. For this study, researchers conducted a meta-analysis of published research to determine safety and efficacy outcomes in this patient population.

Overall, data from 15 trials encompassing 128 patients with CNSL were included. In the overall cohort, 30 patients had PCNSL and 98 patients had SCNSL; among these, the median ages were 56 and 50 years, respectively, the average numbers of prior therapy lines were 3.75 and 4, and 86.67% and 63.35% of patients had received fludarabine-cyclophosphamide conditioning therapy.

Analysis showed that 53% of patients with PCNSL and 48% of patients with SCNSL had any-grade ICANS (18% and 26% had grade 3 or 4 ICANS, respectively). Similarly, 70% and 72% of patients with PCNSL and SCNSL had any-grade cytokine release syndrome, respectively.

CRs were noted in 56% of patients with PCNSL and 47% of patients with SCNSL (37% in both groups had a CR lasting at least 6 months).

“Our report and other recent studies support the expeditious upfront investigation of anti-CD19 CAR T-cell based approaches in PCNSL and SCNSL, where survival outcomes remain significantly inferior to systemic LBCL,” the authors wrote in their report.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ disclosures. 


Cook MR, Dorris CS, Makambi KH, et al. Toxicity and efficacy of CAR T-cell therapy in primary and secondary CNS lymphoma: a meta-analysis of 128 patients. Blood Adv. 2023;7(1):32-39. doi:10.1182/bloodadvances.2022008525