FDA Approves Breyanzi: Novel CAR-T Therapy for Mantle Cell Lymphoma

Key Takeaways

• The FDA granted approval to Breyanzi on May 30, 2024, based on data from the pivotal TRANSCEND NHL 001 trial.
• In the trial, Breyanzi achieved an overall response rate of 85.3% and a complete response rate of 67.6% in patients with relapsed or refractory mantle cell lymphoma.
• The approval includes a Risk Evaluation and Mitigation Strategy due to risks of cytokine release syndrome and neurologic toxicities.
• Mantle cell lymphoma accounts for approximately 3-6% of all non-Hodgkin lymphoma cases, representing an area of high unmet medical need.

What Is Breyanzi?

Breyanzi (lisocabtagene maraleucel) is a CD19-directed genetically modified autologous T-cell immunotherapy developed by Bristol Myers Squibb. It is also being studied for other hematologic malignancies. It was first approved by the FDA in 2021 for large B-cell lymphoma and subsequently expanded to other indications. The therapy involves collecting a patient's own T cells, genetically engineering them to express a chimeric antigen receptor targeting CD19, and infusing them back into the patient. According to the FDA-approved prescribing information, Breyanzi is administered as a single intravenous infusion following lymphodepleting chemotherapy.

Clinical Evidence: TRANSCEND NHL 001 Trial

The FDA approval for mantle cell lymphoma was based on results from the TRANSCEND NHL 001 trial (NCT03483103), a multicenter, single-arm Phase 1/2 study evaluating lisocabtagene maraleucel in patients with relapsed or refractory non-Hodgkin lymphoma. The pivotal efficacy population included adult patients with MCL who had received at least two prior lines of systemic therapy, including a Bruton tyrosine kinase inhibitor.

The study demonstrated durable responses with a median follow-up of 22.2 months. The primary endpoint of overall response rate was 85.3% (95% CI: 74.6-92.7), with a complete response rate of 67.6% (95% CI: 55.2-78.5). The median duration of response was 13.3 months (95% CI: 6.0-23.3).

TRANSCEND NHL 001 Efficacy Results in Mantle Cell Lymphoma

Endpoint	Result	95% Confidence Interval
Overall Response Rate	85.3%	74.6-92.7
Complete Response Rate	67.6%	55.2-78.5
Median Duration of Response	13.3 months	6.0-23.3
Median Follow-up	22.2 months	16.7-22.8

What Are the Safety Considerations?

The FDA approval comes with a Risk Evaluation and Mitigation Strategy due to the potential for severe or life-threatening adverse reactions. The most common adverse reactions occurring in at least 20% of patients include:

• Cytokine release syndrome (CRS)
• Fatigue and musculoskeletal pain
• Encephalopathy and headache
• Edema and decreased appetite
• Infections and cytopenias
• Hypogammaglobulinemia

Management of CRS and neurologic toxicities involves supportive care and immunomodulatory agents such as tocilizumab and corticosteroids, as outlined in the prescribing information. Patients require monitoring in a certified healthcare facility for at least 7 days following infusion.

Regulatory Pathway and Market Context

The FDA granted Breakthrough Therapy designation and Priority Review for Breyanzi in mantle cell lymphoma, based on data suggesting the therapy could offer substantial improvement over available therapies. Approval was granted under the FDA's accelerated approval pathway, with continued approval contingent upon verification of clinical benefit in confirmatory trials.

Mantle cell lymphoma represents approximately 3-6% of all non-Hodgkin lymphoma cases. Historically, patients with relapsed or refractory disease have had limited treatment options and poor prognosis. Breyanzi joins other approved CAR-T therapies in this indication, though it differentiates through its specific manufacturing process and safety profile. The approval was announced in a Bristol Myers Squibb press release on May 30, 2024.

What Are the Next Steps for Patients?

Eligible patients must have relapsed or refractory mantle cell lymphoma following at least two prior lines of systemic therapy, including exposure to a Bruton tyrosine kinase inhibitor. Treatment requires leukapheresis for cell collection, followed by manufacturing of the CAR-T product. Patients receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide before infusion. Treatment is available only at certified healthcare facilities equipped to manage the potential risks of CAR-T therapy.

Frequently Asked Questions

Primary Sources

1. U.S. Food and Drug Administration. FDA Approves Lisocabtagene Maraleucel for Relapsed or Refractory Mantle Cell Lymphoma. May 30, 2024.
2. Breyanzi (lisocabtagene maraleucel) Prescribing Information. Bristol Myers Squibb. Revised May 2024.
3. ClinicalTrials.gov. TRANSCEND NHL 001: Study Evaluating the Safety and Pharmacokinetics of JCAR017 in B-cell Non-Hodgkin Lymphoma. NCT03483103.
4. Bristol Myers Squibb Press Release. U.S. Food and Drug Administration Approves Bristol Myers Squibb's Breyanzi as a New CAR-T Cell Therapy for Relapsed or Refractory Mantle Cell Lymphoma. May 30, 2024.