Tisagenlecleucel demonstrated high sustained remission with a tolerable safety profile among patients with primary central nervous system (PCNSL) lymphoma, according to the results of a phase 1/2 trial published in the journal Blood.

The role of tisagenlecleucel in this population is unknown because patients with PCNSL were excluded from pivotal clinical trials for CD19-targeted chimeric antigen receptor T-cell therapies due to concerns about neurotoxicity. Several retrospective studies, however, suggested that tisagenlecleucel may benefit patients with PCNSL.

This phase 1/2 trial treated 12 patients with relapsed or refractory PCNSL with tisagenlecleucel and followed for a median of 12.2 months.

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At baseline, the median age was 63 and 41.7% of patients had an ECOG performance status of 2 or higher due to progressive neurologic disease. The majority of patients had disease located within the parenchyma, and most was of nongerminal center B-cell origin. The median number of prior lines of therapy was 4 (range, 2-9).

All patients received bridging therapy for symptom control, including disease-related cerebral edema, after leukapheresis and before lymphodepleting chemotherapy. A total of 58.3% of patients responded to treatment, including 50% who achieved a complete response. There were 7 patients alive at data cutoff, including 3 patients with ongoing complete remission.

Cerebrospinal fluid (CSF) of all responders was negative by cytology, flow cytometry, immunoglobulin H sequencing, and MYD88 polymerase chain reaction. CAR T-cells were observed in the CSF, with higher levels of CAR transgene RNA in the CSF of patients who responded to treatment.

Mild or low-grade cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) developed among 58.3% and 41.6% of patients, respectively. There was 1 case of grade 3 ICANS and no treatment-related deaths.

The authors concluded that “the high response rate and acceptable safety profile demonstrated in this study suggests that tisagenlecleucel may offer a valuable option to patients with relapsed or refractory PCNSL.”

Disclosures: This study was funded by Novartis. Please see the original reference for a full list of disclosures.


Frigault MJ, Dietrich J, Gallagher K, et al. Safety and efficacy of tisagenlecleucel in primary CNS lymphoma: a phase 1/2 clinical trial. Blood. 2022;139:2306-2315. doi:10.1182/blood.2021014738