FDA Clears Breyanzi as the First CAR T‑Cell Therapy for Relapsed or Refractory Marginal Zone Lymphoma in the US | iPharmaCenter

FDA Greenlights Breyanzi: Pioneering CAR T-Cell Therapy for Marginal Zone Lymphoma

The U.S. Food and Drug Administration has approved Breyanzi (lisocabtagene maraleucel) for adults battling relapsed or refractory marginal zone lymphoma (MZL) after at least two prior lines of systemic therapy. This groundbreaking decision positions Breyanzi as the first CAR T-cell therapy approved in the U.S. for this challenging rare B-cell malignancy, offering new hope to patients with limited treatment options.

Understanding Breyanzi's Innovative Mechanism

Breyanzi represents a CD19-directed CAR T-cell therapy, where a patient's own T cells are collected via leukapheresis, genetically modified to express chimeric antigen receptors, and infused back as a one-time personalized treatment. Its 4-1BB costimulatory domain plays a key role in promoting the expansion and long-term persistence of these engineered cells, enabling them to effectively target and eliminate cancer cells. Following preparatory lymphodepleting chemotherapy, this approach provides a tailored immunotherapy solution for heavily pretreated individuals.

Promising Results from the TRANSCEND FL Trial

The approval draws from the MZL cohort of the open-label, multicenter, single-arm TRANSCEND FL trial, which enrolled 77 adults with relapsed or refractory MZL after two or more prior therapies or post-stem cell transplant.

Of those, 66 patients received a single Breyanzi infusion, achieving an impressive overall response rate of 95.5%, with 62.1% attaining a complete response confirmed by imaging. These responses demonstrated durability over a median follow-up of 21.6 months, highlighting Breyanzi's potential for sustained disease control.

Side Effects and Safety Considerations

Patients in the trial most commonly experienced cytokine release syndrome (CRS), diarrhea, fatigue, musculoskeletal pain, and headache—adverse events typical of CAR T-cell therapies that are generally manageable with supportive care.

The FDA's Priority Review and Orphan Drug designations underscore the therapy's importance in addressing an unmet need for MZL, a subtype comprising about 7% of non-Hodgkin lymphoma cases.

Expanding Horizons in B-Cell Malignancy Treatment

Developed by Bristol Myers Squibb, Breyanzi now holds approvals across five indications in B-cell cancers, solidifying its place in the evolving landscape of CAR T therapies for hematologic malignancies. This milestone not only broadens treatment possibilities for MZL patients but also signals continued progress in personalized oncology care.