tisagenlecleucel 在原发性 CNS 淋巴瘤中的安全性和有效性：一项 1/2 期临床试验

CD19-directed chimerical antigen receptor T-cell (CAR-T) products have gained US Food and Drug Administration approval for systemic large B-cell lymphoma. Because of concerns about potential immune cell-associated neurotoxicity syndrome (ICANS), patients with primary central nervous system (CNS) lymphoma (PCNSL) were excluded from all pivotal CAR-T studies.

We conducted a phase 1/2 clinical trial of tisagenlecleucel in a highly refractory patients with PCNSL and significant unmet medical need.

Here, we present results of 12 relapsed patients with PCNSL who were treated with tisagenlecleucel and followed for a median time of 12. 2 months (range, 3. 64-23. 5). Grade 1 cytokine release syndrome was observed in 7/12 patients (58. 3%), low-grade ICANS in 5/12 (41. 6%) patients, and only 1 patient experienced grade 3 ICANS. Seven of 12 patients (58.

3%) demonstrated response, including a complete response in 6/12 patients (50%). There were no treatment-related deaths. Three patients had ongoing complete remission at data cutoff. Tisagenlecleucel expanded in the peripheral blood and trafficked to the CNS. Exploratory analysis identified T-cell, CAR T, and macrophage gene signatures in cerebrospinal fluid following infusion when compared with baseline.

Overall, tisagenlecleucel was well tolerated and resulted in a sustained remission in 3/7 (42. 9%) of initial responders. These data suggest that tisagenlecleucel is safe and effective in this highly refractory patient population. This trial was registered at www. clinicaltrials. gov as #NCT02445248.