FDA Approves Breyanzi as First CAR T-Cell Therapy for Relapsed/Refractory Marginal Zone Lymphoma

The U.S. Food and Drug Administration (FDA) has approved a new indication for Breyanzi (lisocabtagene maraleucel), making it the first Chimeric Antigen Receptor (CAR) T-cell therapy available in the US for adults with relapsed or refractory (R/R) marginal zone lymphoma (MZL) who have failed or relapsed after two or more prior lines of systemic therapy.

Breyanzi is a CD19-directed CAR T-cell therapy that genetically modifies a patient’s own T-cells to target and destroy cancer cells. This approval marks a significant advancement for patients with MZL, a subtype of indolent non-Hodgkin lymphoma, who often experience multiple relapses and limited treatment options after initial therapies.

Clinical Trial Evidence

Breyanzi’s approval is based on results from the MZL cohort of the TRANSCEND FL trial (NCT04245839), an open-label, multicenter, phase 2 single-arm study. In the primary efficacy analysis set (n=66), Breyanzi demonstrated an overall response rate (ORR) of 95.5%, with a well-established safety profile. The treatment process involves blood collection, CAR T-cell production, lymphodepleting chemotherapy, infusion, and monitoring for side effects such as cytokine release syndrome (CRS) and neurologic toxicities.

Breyanzi (lisocabtagene maraleucel) carries a boxed warning, the FDA’s most serious alert, for cytokine release syndrome (CRS), neurologic toxicities, and secondary hematological malignancies

Cytokine Release Syndrome (CRS)

CRS occurs in patients receiving Breyanzi and can cause fatal or life-threatening reactions, including fever, low blood pressure, and organ failure. Patients must remain within 2 weeks of the infusion site for monitoring, and severe cases require prompt treatment with tocilizumab or other interventions. Do not administer Breyanzi to patients with active infections or uncontrolled conditions that heighten CRS risk.

Neurologic Toxicities

Neurologic events, including immune effector cell-associated neurotoxicity syndrome (ICANS), confusion, seizures, and cerebral edema, have been fatal in some cases following Breyanzi infusion. Patients should avoid driving or hazardous activities for at least 8 weeks post-infusion due to prolonged risks. Monitoring for at least 4 weeks after infusion is essential, with REMS programs in place to manage these effects.

Secondary Hematological Malignancies

T-cell malignancies, including CAR-positive tumors, have occurred post-treatment with CD19-directed therapies like Breyanzi, presenting as early as weeks after infusion and potentially leading to death. This risk prompted a 2024 FDA labeling update applicable to all BCMA- and CD19-directed CAR T therapies, requiring long-term patient monitoring. Physicians must inform patients of this serious outcome and report cases to FDA systems

Lynelle B. Hoch, president of Bristol Myers Squibb’s Cell Therapy Organization, highlighted Breyanzi as the first and only CAR T-cell therapy approved for relapsed or refractory marginal zone lymphoma, reflecting the company’s commitment to expanding patient access to innovative treatments. Dr. M. Lia Palomba of Memorial Sloan Kettering Cancer Center noted the FDA approval represents a significant advancement, offering patients with multiple relapses a treatment option with high response rates and an established safety profile.

Breyanzi is now the only CAR T-cell therapy approved by the FDA for five different cancer types, including large B-cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, follicular lymphoma, mantle cell lymphoma, and now marginal zone lymphoma.