Safety and Efficacy of Tisagenlecleucel in Primary CNS Lymphoma: A phase I/II clinical trial
Mené sur 12 patients atteints d'un lymphome primitif du système nerveux central récidivant, cet essai de phase I/II évalue l'efficacité, du point de vue du taux de réponse, du tisagenlecleucel (une immunothérapie à base de lymphocytes CAR-T ciblant CD19) et sa toxicité
CD19 directed CAR-T products have gained FDA approval for systemic large B-cell lymphoma. Due to concerns about potential immune cell associated neurotoxicity syndrome (ICANS), patients with primary CNS lymphoma (PCNSL) were excluded from all pivotal CAR-T studies. We conducted a phase I/II clinical trial of tisagenlecleucel in a highly refractory PCNSL patient population with significant unmet medical need (Clinicaltrials.gov; NCT02445248). Here we present results of twelve relapsed PCNSL patients who were treated with tisagenlecleucel and followed for a median time of 12.2 months (range, 3.64 to 23.5 months). Grade 1 CRS was observed in 7/12 patients (58.3%), low grade ICANS in 5/12 (41.6%) patients and only one patient experienced grade 3 ICANS. 7/12 patients (58.3%) demonstrated response, including a complete response (CR) in 6/12 patients (50%). There were no treatment-related deaths. Three patients had ongoing complete remission at data cut off. Tisagenlecleucel expanded in the peripheral blood and trafficked to the CNS. Exploratory analysis identified T-cell, CAR T-cell and macrophage gene signatures in cerebrospinal fluid (CSF) following infusion when compared to 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. Registered as Clinical Trial # NCT04134117
Blood 2022