FDA Approves Breyanzi for Relapsed or Refractory Mantle Cell Lymphoma

The FDA has approved Bristol Myers Squibb’s (BMS) Breyanzi (lisocabtagene maraleucel) to treat adults with relapsed or refractory (R/R) mantle cell lymphoma (MCL) who were previously administered at least two lines of systemic therapy that included a Bruton tyrosine kinase (BTK) inhibitor.¹ The regulatory action marks the fourth indication for Breyanzi to treat a distinct subtype of non-Hodgkin lymphoma.

“With Breyanzi, we are delivering on the promise of cell therapy by offering a definitive treatment option for some of the most difficult-to-treat lymphomas,” Bryan Campbell, senior vice president, head of Commercial, Cell Therapy, BMS, said in a press release. “We are proud of the advances we are making to bring our differentiated CAR T cell therapy to the most patients across indications and lines of therapy to ensure treatment options that provide improved outcomes are available when most needed.”¹

Breyanzi is a CD19-directed chimeric antigen receptor (CAR) T-cell therapy that is made from a patient’s own T cells. The cells are taken from a patient and genetically reengineered to become CAR T cells, which are subsequently infused back into the patient via a one-time infusion.

This is the third approval for Breyanzi in the past few months for a hematologic malignancy. On May 15, the FDA granted the CAR T-cell therapy accelerated approval for the treatment of adult patients with R/R follicular lymphoma who previously received two or more lines of systemic therapy.² This followed an accelerated approval granted in March for Breyanzi to treat adult patients with R/R chronic lymphocytic leukemia or small lymphocytic lymphoma who were previously administered at least two lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.³

The latest approval was based on findings from the MCL cohort of the open-label, multicenter, pivotal TRANSCEND NHL 001 (NCT02631044) trial. Investigators enrolled adult patients with R/R MCL who were previously administered at least two or more prior lines of therapy, including a BTK inhibitor.

Among patients administered Breyanzi who were evaluated for efficacy (n=68), 85.3% (95% CI: 74.6-92.7) responded to treatment and 67.6% (95% CI: 55.2-78.5) achieved a complete response (CR). The responses in patients administered Breyanzi were found to be rapid and durable, with a median time to response of one month (range: 0.7-3) and median duration of response (DOR) of 13.3 months (95% CI: 6.0-23.3), with a median follow-up of 22.2 months (95% CI: 16.7-22.8).

More than half (51.4%; 95% CI: 37.5-63.7) of patients who responded to treatment remained in response at 12 months, with 38.8% (95% CI: 25-52.4) remaining in response at 18 months. A primary analysis published in the Journal of Clinical Oncology (n=83; DL1 + DL2) demonstrated an overall response rate of 83.1% (95% CI: 73.3-90.5), a CR rate of 72.3% (95% CI: 61.4 to 81.6), median DOR of 15.7 months (95% CI: 6.2 to 24.0), and progression-free survival of 15.3 months (95% CI: 6.6 to 24.9).

In terms of safety, the profile of Breyanzi was consistent across clinical trials (n=702). Any grade cytokine release syndrome (CRS) was reported in 54% of patients, which included Grade >3 CRS in 3.2% of patients.

“There have been few advances in the treatment of relapsed or refractory MCL, and prognosis worsens for patients after each subsequent relapse, often leaving them with high disease burden and difficulty achieving deep and durable responses,” lead trial investigator Michael Wang, MD, Puddin Clarke Endowed Professor, Department of Lymphoma and Myeloma, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, said in a press release. “The approval of Breyanzi offers an important new CAR T treatment option with high rates of lasting responses and a consistent safety profile, which is critically important for these patients who currently have limited options to treat this aggressive disease.”¹

References

1. 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. News release. Bristol Myers Squibb. May 30, 2024. Accessed May 30, 2024. https://news.bms.com/news/details/2024/U.S.-Food-and-Drug-Administration-Approves-Bristol-Myers-Squibbs-Breyanzi-as-a-New-CAR-T-Cell-Therapy-for-Relapsed-or-Refractory-Mantle-Cell-Lymphoma/default.aspx

2. Bristol Myers Squibb’s CAR T Cell Therapy Breyanzi Approved by the U.S. Food and Drug Administration for Relapsed or Refractory Follicular Lymphoma. News release. Bristol Myers Squibb. May 15, 2024. Accessed May 30, 2024. https://news.bms.com/news/details/2024/Bristol-Myers-Squibbs-CAR-T-Cell-Therapy-Breyanzi-Approved-by-the-U.S.-Food-and-Drug-Administration-for-Relapsed-or-Refractory-Follicular-Lymphoma/default.aspx

3. US FDA approves Bristol Myers Squibb’s Breyanzi ® as the first and only CAR T cell therapy for adults with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). News release. Bristol Myers Squibb. March 14, 2024. Accessed May 30, 2024. https://news.bms.com/news/details/2024/U.S.-FDA-Approves-Bristol-Myers-Squibbs-Breyanzi--as-the-First-and-Only-CAR-T-Cell-Therapy-for-Adults-with-Relapsed-or-Refractory-Chronic-Lymphocytic-Leukemia-CLL-or-Small-Lymphocytic-Lymphoma-SLL/default.aspx