New CAR-T for Aggressive B-Cell Lymphoma Wins FDA Nod

WASHINGTON -- The FDA approved lisocabtagene maraleucel (Breyanzi), a chimeric antigen receptor (CAR) T-cell therapy, on Friday for treating relapsed or refractory non-Hodgkin lymphoma.

The agent is indicated for patients with large B-cell lymphoma -- including diffuse large B-cell lymphoma (DLBCL) -- who have failed a minimum of two prior systemic treatments.

"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," Peter Marks, MD, PhD, director of FDA's Center for Biologics Evaluation and Research, said in a statement. "Gene and cell therapies have evolved from promising concepts to practical cancer treatment regimens."

Support for approval came from TRANSCEND NHL 001, which evaluated lisocabtagene maraleucel in over 250 patients with relapsed or refractory large B-cell lymphoma, including DLBCL. The single-arm study demonstrated an overall response rate of 73%, with 54% of patients achieving a complete remission, according to the FDA.

Lisocabtagene maraleucel marks the fourth CAR T-cell product approved in lymphoma, following axicabtagene ciloleucel (Yescarta) and tisagenlecleucel (Kymriah) for large B-cell lymphoma, and brexucabtagene autoleucel (Tecartus) in mantle cell lymphoma.

FDA specified that lisocabtagene maraleucel is not approved for primary central nervous system lymphoma.

Like other CAR T-cell therapies, lisocabtagene maraleucel carries the risk of severe side effects, and the labeling will include a boxed warning for cytokine release syndrome (CRS), which can cause life-threatening neurological events, among other symptoms. Other adverse events (AEs) seen in TRANSCEND NHL 001 included hypersensitivity reactions, infections, low blood cell counts, and immune suppression, with most occurring early on in treatment.

Due to the risk of CRS and severe neurologic AEs, the FDA has required a risk evaluation and mitigation strategy (REMS) for lisocabtagene maraleucel, and patients must be informed to watch for signs and symptoms of these side effects. The REMS includes elements to assure safe use (ETASU).

"FDA is requiring, among other things, that healthcare facilities that dispense Breyanzi be specially certified," the agency noted. "As part of that certification, staff involved in the prescribing, dispensing or administering of Breyanzi are required to be trained to recognize and manage the risks of CRS and neurologic toxicities."

FDA will also require manufacturer Bristol Myers Squibb to conduct a post-marketing observational safety study.

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