The US Food and Drug Administration has approved CD19-targeted chimeric antigen receptor T-cell (CAR-T) products for systemic large B-cell lymphoma. Patients with primary central nervous system (CNS) lymphoma (PCNSL) were excluded from all critical CAR-T studies due to concerns regarding immune cell-associated neurotoxicity syndrome (ICANS). For a study, researchers performed a phase 1/2 clinical trial of tisagenlecleucel in individuals with PCNSL who were very refractory and had severe unmet medical need.
They described the findings of 12 relapsed PCNSL patients who were treated with tisagenlecleucel and monitored for a median of 12.2 months (range, 3.64-23.5). Grade 1 cytokine release syndrome was detected in 7/12 patients (58.3%), low-grade ICANS in 5/12 (41.6%), and grade 3 ICANS in just 1 patient.
In 7 of the 12 patients (58.3%) responded, with 6 of the 12 patients demonstrating a full response (50%). No one died as a result of the therapy. At the time of the data cutoff, three patients were still completely remission. Tisagenlecleucel grew in the peripheral circulation and was transported to the brain. When T-cell, CAR T, and macrophage gene profiles were compared to baseline in cerebrospinal fluid post infusion, exploratory analysis revealed T-cell, CAR T, and macrophage gene signatures. Overall, tisagenlecleucel was well tolerated and resulted in remission in 3/7 (42.9%) of early responders. The findings indicated that tisagenlecleucel was both safe and effective in the high-risk patient population.
