The US Food and Drug Administration (FDA) has approved lisocabtagene maraleucel (Breyanzi), a chimeric antigen receptor (CAR) T-cell product for the treatment of adults with certain types of relapsed or refractory large B-cell lymphoma who relapse or fail to respond to at least two systemic treatments.
The new approval comes with a risk evaluation and mitigation strategy (REMS) because of the risk for serious adverse events, including cytokine release syndrome (CRS).
The product, from Juno Therapeutics, a Bristol Myers Squibb company, is the third gene therapy to receive FDA approval for non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL). DLBCL is the most common type of non-Hodgkin lymphoma in adults, accounting for about a third of the approximately 77,000 cases diagnosed each year in the United States.
The FDA previously granted Breyanzi orphan drug, regenerative medicine advanced therapy (RMAT), and breakthrough therapy designations. The product is the first therapy with an RMAT designation to be licensed by the agency.
The new approval is based on efficacy and safety demonstrated in a pivotal phase 1 trial of more than 250 adults with relapsed or refractory large B-cell lymphoma. The complete remission rate after treatment with Breyanzi was 54%.
“Treatment with Breyanzi has the potential to cause severe side effects. The labeling carries a boxed warning for cytokine release syndrome (CRS), which is a systemic response to the activation and proliferation of CAR T cells, causing high fever and flu-like symptoms and neurologic toxicities,” the FDA explains. “Both CRS and neurological events can be life-threatening.”
Other side effects, which typically present within 1-2 weeks after treatment, include hypersensitivity reactions, serious infections, low blood cell counts, and a weakened immune system, but some side effects may occur later.
The REMS requires special certification for facilities that dispense the product and “specifies that patients be informed of the signs and symptoms of CRS and neurological toxicities following infusion — and of the importance of promptly returning to the treatment site if they develop fever or other adverse reactions after receiving treatment with Breyanzi,” the FDA notes.
Breyanzi is not indicated for patients with primary central nervous system lymphoma, the FDA notes.
Facility certification involves training to recognize and manage the risks of CRS and neurologic toxicities.
A postmarketing study to further evaluate the long-term safety will also be required.
Sharon Worcester is a reporter for MDedge News, part of the Medscape Professional Network.