Abstract
Tisagenlecleucel has an acceptable safety profile and showed preliminary evidence of CNS efficacy.
Major Finding: Tisagenlecleucel has an acceptable safety profile and showed preliminary evidence of CNS efficacy.
Concept: Patients with CNS involvement have been largely excluded from previous CAR T-cell clinical trials in lymphoma.
Impact: A trial in primary CNS lymphoma is planned; further trials in secondary CNS lymphoma are warranted.
Although clinical trials support the use of chimeric antigen receptor T-cell (CAR-T) therapies targeting CD19 for relapsed or treatment-refractory B-cell non-Hodgkins lymphoma, patients with central nervous system (CNS) involvement have typically been excluded due to concerns about neurotoxicity. In a retrospective study, Frigault and colleagues analyzed the effects of the CAR-T therapy tisagenlecleucel—selected for its lower reported rates of neurotoxicity and cytokine release syndrome—following lymphodepleting chemotherapy with cyclophosphamide and fludarabine in 8 patients with secondary CNS lymphoma. Patients had been heavily pretreated, with a median of 5 prior therapies; one patient had previously received an allogenic stem cell transplant. The safety profile was acceptable, with no patients exhibiting cytokine-release syndrome or neurotoxicity that required tocilizumab or high-dose steroid treatment. Two patients died within 30 days of CAR-T infusion; autopsies revealed that these patients died of progressive disease and not as a direct result of the treatment. The other patients experienced partial or complete responses, indicating the treatment's potential in this patient population; however, the short follow-up period (up to 180 days) was a limitation of the study. These findings indicate that additional studies of tisagenlecleucel in secondary CNS lymphoma are justified. Further expanding on this work, Frigault and colleagues are arranging a pilot study of tisagenlecleucel in primary CNS lymphoma.
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