FDA Approves Breyanzi CAR-T Cell Therapy for Relapsed/Refractory Marginal Zone Lymphoma
核心洞察
The FDA has approved lisocabtagene maraleucel (Breyanzi) for adult patients with relapsed or refractory marginal zone lymphoma (搜索) following at least two prior lines of therapy.
The approval is based on the TRANSCEND FL-MZL trial, which demonstrated an overall response rate of 84.4% and complete response rate of 55.8% in the intent-to-treat population.
The CD19 (搜索)-directed CAR-T cell therapy showed a median duration of response that was not reached, indicating potentially durable responses in this patient population.
The U.S. Food and Drug Administration has approved lisocabtagene maraleucel (Breyanzi) for the treatment of adult patients with relapsed or refractory marginal zone lymphoma (搜索) (MZL) following at least two prior lines of therapy. This approval represents a significant advancement for patients with this rare form of B-cell lymphoma who have exhausted multiple treatment options.
Clinical Trial Results Drive Approval
The approval is supported by data from the TRANSCEND FL-MZL trial, an open-label, multicenter, single-arm phase 2 study that evaluated Breyanzi in patients with relapsed/refractory MZL. The trial included patients who had received two or more lines of prior therapy following hematopoietic stem cell transplant, with participants having an ECOG performance status of 1 or less.
In the intent-to-treat population, the overall response rate (ORR) reached 84.4% (95% CI, 74.4%-91.7%), while the complete response rate (CRR) was 55.8% (95% CI, 44.1%-67.2%). Notably, the median duration of response was not reached (95% CI, 25.59-NR), suggesting potentially durable responses in this patient population.
The efficacy analyses were performed in 77 leukapheresed patients and in 66 patients who had confirmed measurable disease by CT scan at baseline, received conforming product in the intended dose range, and had at least nine months of follow-up from the date of first response.
Treatment Protocol and Administration
Breyanzi is recommended at a dose of 90 to 110 x 10⁶ CAR-positive T cells with a 1:1 ratio of CD4 and CD8 components. Patients receive a single dose of Breyanzi two to seven days after the completion of lymphodepleting chemotherapy.
As a CAR-T cell therapy, Breyanzi is manufactured using a patient's own T cells. A gene for a chimeric antigen receptor (CAR) is added to the T cells in the laboratory, and these modified CAR-T cells are grown in large numbers before being infused back into the patient. The therapy binds to CD19 (搜索), a protein found on most B-cell lymphoma cells, helping the body's immune system target and kill cancer cells.
Safety Profile and Risk Management
According to Bristol Myers Squibb (搜索), the developer of Breyanzi, the therapy demonstrated a safety profile consistent with prior findings in the TRANSCEND FL-MZL trial. The prescribing information includes warnings and precautions for several adverse events, including cytokine release syndrome (搜索) (CRS), neurologic toxicities, hypersensitivity reactions, serious infections, prolonged cytopenias, hypogammaglobulinemia, secondary malignancies, and immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome.
Beth Faiman, PhD, MSN, APN-BC, BMTCN, AOCN, FAAN, FAPO, noted that T-cell engagers often can induce cytokine release syndrome (搜索) across disease states. "What we're doing is taking the marker target on the cell—for example, CD20 (搜索)—and then CD3 (搜索), like a helping hand, will bring it together and cause cell death when you're directing these T cells. That causes a cytokine storm and a whole host of problems. [...] That cytokine release syndrome and the neurotoxicity syndrome are constants, regardless of the disease state."
The FDA previously had a Risk Evaluation and Mitigation Strategy (REMS) protocol in place for monitoring and mitigating certain safety events in patients receiving Breyanzi. These guidelines were removed in June, with the FDA reducing driving restrictions for patients from eight weeks to two weeks after treatment.
Expanding Treatment Landscape
This approval adds to Breyanzi's growing list of indications. The therapy was previously approved in May 2024 for use in previously treated relapsed/refractory follicular lymphoma (搜索) and mantle cell lymphoma (搜索), both based on findings from the TRANSCEND FL-MZL trial. Breyanzi also received approval in June 2022 for second-line treatment of patients with relapsed or refractory large B-cell lymphoma (搜索).
Rosanna Ricafort, vice president and Senior Global Program Lead for Hematology and Cell Therapy at Bristol Myers Squibb (搜索), emphasized the clinical need addressed by this approval: "While initial therapy for marginal zone lymphoma (搜索) can be effective, multiple relapses over the course of several years are common, leaving patients in need of a new treatment option that can provide high, lasting response rates."