CD19-Directed CAR-T Has 'Encouraging Efficacy' in CNS Lymphoma

CD19-directed chimeric antigen receptor (CAR) T-cell therapy led to a complete remission in approximately half of patients with relapsed/refractory central nervous system (CNS) lymphoma, according to a recent analysis.

Michael Roderick Cook, MD, of Georgetown University Medical Center, and colleagues performed the research because patients with primary or secondary CNS lymphoma who received anti-CD19 CAR T-cells had responses in early studies of the therapy, but the sample sizes were small.

Dr. Cook and colleagues conducted the systematic review and meta-analysis using all published data describing CAR-T treatment in patients with primary or secondary CNS lymphoma. They identified 30 patients with primary CNS lymphoma and 98 patients with secondary CNS lymphoma. Their primary objectives were to evaluate toxicity specific to CAR-T therapy and patient response rates.

A complete remission occurred in 56% of patients with primary CNS lymphoma, with 37% remaining in remission at six months, while 47% of patients with secondary CNS lymphoma had a complete remission and 37% remained in remission at six months.

Cytokine release syndrome of any grade occurred in 70% of patients with primary CNS lymphoma, and in 72% of patients with secondary CNS lymphoma. Grade 3 to grade 4 cytokine release syndrome occurred in 13% of patients with primary CNS lymphoma and in 11% with secondary CNS lymphoma.

Immune effector cell-associated neurotoxicity syndrome of any grade occurred in 53% of patients with primary CNS lymphoma and in 48% with secondary CNS lymphoma, with grade 3 to grade 4 immune effector cell-associated neurotoxicity syndrome occurring in 18% and 26% of patients, respectively.

“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 [large B-cell lymphoma], with no increased signal of neurotoxicity observed,” Dr. Cook and colleagues concluded. “Encouraging efficacy was demonstrated in patients with CNS lymphoma, with no discernible differences between [primary CNS lymphoma] and [secondary CNS lymphoma].”

Reference

Cook MR, Dorris CS, Makambi KH, et al. Toxicity and efficacy of CAR T-cell therapy in PCNSL and SCNSL: a meta-analysis of 128 patients. Blood Adv. 2022. doi:10.1182/bloodadvances.2022008525