On February 5, 2021, the FDA approved lisocabtagene maraleucel (Breyanzi; Juno Therapeutics), a new CD19-directed chimeric antigen receptor (CAR) T-cell therapy, for the treatment of adults with relapsed or refractory large B-cell lymphoma (LBCL) after ≥2 previous lines of systemic therapy. The FDA granted lisocabtagene maraleucel priority review, as well as breakthrough therapy, orphan drug, and regenerative medicine advanced therapy designations.
“Today’s approval represents another milestone in the rapidly progressing field of gene therapy by providing an additional treatment option for adults with certain types of cancer affecting the blood, bone marrow, and lymph nodes,” said Peter Marks, MD, PhD, Director of the FDA’s Center for Biologics Evaluation and Research.
This approval was based on data from the single-arm, open-label, multicenter TRANSCEND clinical trial of 192 adults with relapsed or refractory LBCL who had received lymphodepleting chemotherapy and ≥2 lines of therapy.
The overall response rate was 73% (95% confidence interval [CI], 67-80), including 54% (N = 104) complete responses (95% CI, 47-61). The median time to first response was 1 month. Of those who had a complete response, the duration of response (DOR) was ≥6 months in 65% and ≥9 months in 62%. The median DOR was 1.4 months in the patients with a partial response and was not reached in those with complete responses (95% CI, 16.7-not reached).
The most common (46%) adverse event was cytokine release syndrome (CRS), and 35% of all patients had a neurologic adverse event (grade ≥3, 12%), including 3 fatal cases. Other grade ≥3 adverse reactions included cytopenia (31%) and infection (19%). Because lisocabtagene maraleucel is associated with a risk for life-threatening CRS and other neurologic effects, the drug is only available through a REMS program.