Bristol Myers Squibb Breyanzi gets USFDA nod for Relapsed or Refractory Mantle Cell 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,” said Bryan Campbell, senior vice president, Head of Commercial, Cell Therapy, Bristol Myers Squibb. “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.”

MCL is a rare but aggressive form of non-Hodgkin lymphoma, and many patients relapse or become resistant to frontline therapies. Currently, MCL is considered an incurable disease, and response rates and duration of response tend to decrease with each additional relapse.

“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,” said Michael Wang, M.D., lead investigator and Puddin Clarke Endowed Professor, Department of Lymphoma and Myeloma, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas. “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.”

The approval of Breyanzi is based on results from the MCL cohort of TRANSCEND NHL 001, which enrolled adults with relapsed or refractory MCL who had previously received at least two or more prior lines of therapy, including a BTK inhibitor. Based on the U.S. Prescribing Information (USPI), in patients treated with Breyanzi and evaluated for efficacy (n=68), 85.3% (95% CI: 74.6-92.7) responded to treatment, with 67.6% (95% CI: 55.2-78.5) achieving a complete response (CR). Responses were assessed per the 2014 Lugano classification and required bone marrow biopsy to confirm CR. Responses were rapid and durable with a median time to response of one month (range: 0.7-3) and median duration of response 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 responders remained in response at 12 months, and 38.8% (95% CI: 25-52.4) of responders remained in response at 18 months. Results from the primary analysis published in the Journal of Clinical Oncology (JCO) (n=83; DL1 + DL2) showed an overall response rate of 83.1% (95% CI: 73.3-90.5) and a CR rate of 72.3% (95% CI: 61.4 to 81.6). Median duration of response was 15.7 months (95% CI: 6.2 to 24.0) and progression-free survival was 15.3 months (95% CI: 6.6 to 24.9).

Breyanzi has exhibited a consistent safety profile across clinical trials (n=702) with any grade cytokine release syndrome (CRS) occurring in 54% of patients, including Grade >3 CRS in 3.2% of patients. The median time to onset was 5 days (range: 1 to 63 days). Any grade neurologic events (NEs) were reported in 31% of patients, including Grade >3 in 10% of patients. The median time to onset of NEs was 8 days (range: 1 to 63 days). NEs resolved in 88% of patients with a median duration of 7 days (range: 1 to 119 days). The safety profile of Breyanzi allows for the option of outpatient treatment and management of patients. Breyanzi was administered in the inpatient and outpatient setting in the MCL cohort of TRANSCEND NHL 001.

“The approval of Breyanzi brings a new CAR T cell therapy option to patients battling relapsed or refractory MCL,” said Meghan Gutierrez, chief executive officer, Lymphoma Research Foundation. “Each advance in treatment represents important progress in improving outcomes for patients, and this news builds upon this progress with a new potentially transformative treatment where there are currently limited options. We are thankful for the families and the researchers involved in making this approval a reality for those living with this disease.”

"To support this additional indication for Breyanzi, Bristol Myers Squibb has made continuous investments to increase manufacturing capacity and is prepared to meet demand for Breyanzi," the Company stated.

Breyanzi is broadly covered by commercial and government insurance programs in the U.S.

Breyanzi is a CD19-directed CAR T cell therapy with a 4-1BB costimulatory domain, which enhances the expansion and persistence of the CAR T cells. Breyanzi is made from a patient’s own T cells, which are collected and genetically reengineered to become CAR T cells that are then delivered via infusion as a one-time treatment.

Breyanzi is approved in the U.S. for the treatment of relapsed or refractory large B-cell lymphoma (LBCL) after at least one prior line of therapy, and has received accelerated approval for the treatment of relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma after at least two prior lines of therapy, and relapsed or refractory follicular lymphoma in the third-line plus setting. Breyanzi is also approved in Japan, the European Union (EU), and Switzerland for the second-line treatment of relapsed or refractory LBCL, and in Japan, the EU, Switzerland, the UK and Canada for relapsed and refractory LBCL after two or more lines of systemic therapy.

Bristol Myers Squibb’s clinical development program for Breyanzi includes clinical studies in other types of lymphoma.