CD19 chimeric antigen receptor (CAR) T-cell (CAR-T) therapy tisagenlecleucel (Kymriah®) appeared safe and showed clinical activity in patients with secondary central nervous system (CNS) lymphoma, according to a retrospective cohort analysis of a small group of patients who were treated at a single institution. The findings were published online July 18, 2019 in Blood.

Currently, Kymriah is indicated for patients with relapsed or refractory large B-cell lymphoma, and the drug label explicitly excludes patients with primary CNS lymphoma from the indication. Patients with secondary CNS lymphoma, however, are not explicitly excluded.

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The cohort consisted of 8 patients who had high-grade B-cell lymphoma with secondary CNS involvement and were treated with tisagenlecleucel at Massachusetts General Hospital, Boston, between August 2018 and March 2019. Patients were heavily pretreated, having had a median of 5 prior therapies (range, 3-6).


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Neurotoxicity higher than grade 1 was not observed in any of the patients; in addition, neither tocilizumab nor steroids were needed to manage toxicity related to CAR-T in any of the patients.

At 28 days after CAR-T infusion, 1 patient had a complete response (CR) with an ongoing response at 90 days. A second patient initially had a CR at 28 days, followed by a systemic relapse at 90 days. One patient initially had a partial response (PR) at 28 days and then achieved a CR at 180 days. A different patient achieved a PR at 28 days and maintained that response at 90 days.

“Our findings suggest that the use of commercial tisagenlecleucel CAR-T for isolated secondary CNS lymphoma may be a viable treatment option for this otherwise challenging patient population,” the study authors wrote. “Due to these promising results we plan to proceed with a pilot study of tisagenlecleucel in primary CNS lymphoma this coming year.”

Reference

Frigault MJ, Dietrich J, Martinez-Lage M, et al. Tisagenlecleucel CAR-T cell therapy in secondary CNS lymphoma [published online July 18, 2019]. Blood. doi: 10.1182/blood.2019001694