Bristol Myers Squibb’s Breyanzi has received U.S. Food and Drug Administration approval for the treatment of marginal zone lymphoma (MZL), making it the first CAR-T therapy authorized for this specific indication. The clearance also marks Breyanzi as the first CAR-T therapy to obtain approval across five distinct blood cancer types.
The FDA has authorized the one-time infused, CD19-directed cell therapy for adults with relapsed or refractory MZL who have undergone at least two prior lines of treatment. Breyanzi initially entered the market in 2021 with approval for large B-cell lymphoma and later gained additional authorizations for mantle cell lymphoma, follicular lymphoma, chronic lymphocytic lymphoma, and small lymphocytic lymphoma. This new approval places the therapy ahead of Gilead’s CD19-targeted Yescarta and Tecartus, which together hold approvals in four blood cancer indications.
MZL represents approximately 7% of non-Hodgkin’s lymphoma cases. This slow-moving disease emerges when white blood cells gather in lymph nodes or organs. While initial therapy often leads to remission, relapse is frequent and can take place multiple times over several years. In some patients, the condition can progress into large B-cell lymphoma, which is more aggressive.
The FDA highlighted the significance of the authorization, with Vinay Prasad, M.D., director of the FDA’s Center for Biologics Evaluation and Research, stating, “Today’s approval represents a major advancement in precision medicine, essentially turning the patient’s immune system into a more effective tool to treat MZL,” in the agency’s announcement.
The regulatory decision was supported by findings from the phase 2 Transcend FL study. The trial enrolled 66 patients with MZL and recorded an overall response rate of 95%, with 62% of participants reaching a complete response. Among those who responded, 90% retained their response at the 24-month mark.
Study investigator M. Lia Palomba, M.D., of Memorial Sloan Kettering Cancer Center, noted a substantial need for therapeutic options that offer lasting benefit for patients with MZL. She described the FDA’s decision as a significant step in adjusting the treatment landscape and providing patients with an option that has shown strong response rates alongside an established safety profile.
In the MZL portion of the study, any-grade cytokine release syndrome appeared in 76% of participants. Reported nervous system-related events included headache and tremor in 21% of patients, encephalopathy in 21%, dizziness in 16%, and aphasia in 10%, according to Bristol Myers Squibb.
In the broader CAR-T market, BMS continues to expand Breyanzi’s commercial presence while competing with Gilead. Yescarta, first approved in 2017, reached blockbuster status in 2022 with $1.6 billion in annual revenue, supplemented by $403 million from Tecartus. However, in the most recent quarter, Gilead reported declines of 10% for Yescarta and 15% for Tecartus, with combined quarterly sales of $432 million.
During the same period, BMS reported that Breyanzi revenue rose 58% to $359 million. With cumulative sales of $907 million this year, Breyanzi is on track to achieve blockbuster status for the first time. Bristol Myers Squibb originally obtained Breyanzi through its $74 billion acquisition of Celgene in 2019, shortly after Celgene secured the therapy through its $9 billion purchase of Juno Therapeutics.
Despite the enthusiasm surrounding this new indication, experts emphasize that real-world adoption will take time. CAR-T therapies like Breyanzi require highly specialized infrastructure and trained clinical teams to administer and monitor patients, particularly given the potential for serious side effects such as cytokine release syndrome and neurologic events. As a result, many treatment centers are continuing to build capacity and refine best practices to ensure patient safety while maximizing therapeutic benefit.
The broader impact of the FDA’s decision is expected to extend beyond marginal zone lymphoma. With approval across five different blood cancer types, Breyanzi now sets a new benchmark for CAR-T therapies targeting CD19, highlighting how advanced cell therapies are reshaping the landscape of hematologic oncology. This trend reflects ongoing progress in precision medicine, where the patient’s own immune system is harnessed to deliver highly targeted cancer treatment.
