Safety and efficacy of tisagenlecleucel in primary CNS lymphoma: a phase 1/2 clinical trial

Blood. 2022 Apr 14;139(15):2306-2315. doi: 10.1182/blood.2021014738.


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 as #NCT02445248.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II

MeSH terms

  • Antigens, CD19 / therapeutic use
  • Central Nervous System Neoplasms* / therapy
  • Humans
  • Immunotherapy, Adoptive* / adverse effects
  • Lymphoma* / therapy
  • Receptors, Antigen, T-Cell* / therapeutic use
  • Receptors, Chimeric Antigen / therapeutic use


  • Antigens, CD19
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen
  • tisagenlecleucel

Associated data