The Food and Drug Administration (FDA) has approved Breyanzi (lisocabtagene maraleucel; Bristol Myers Squibb) for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after 2 or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B.
Breyanzi is a CD19-directed genetically modified autologous T cell immunotherapy administered as a defined composition of chimeric antigen receptor (CAR)-positive viable T cells (consisting of CD8 and CD4 components). It is a customized treatment created using a patient’s own T cells that have been genetically modified to include a new gene to target and destroy lymphoma cells.
The approval was based on data from a pivotal phase 1 study (TRANSCEND NHL 001) that assessed the efficacy and safety of Breyanzi in 268 patients with relapsed or refractory large B-cell non-Hodgkin lymphoma (NHL) after at least 2 lines of therapy. The primary outcome measures included treatment-related adverse events, dose-limiting toxicities and objective response rate (ORR). Key secondary end points included complete response rate, duration of response (DOR), and progression-free survival (PFS).
Among 192 patients in the main efficacy population, the ORR was 73% (95% CI, 67-80), of which 54% of patients (95% CI, 47-61) had complete response (CR) and 19% (95% CI, 14-26) had partial response (PR). The median DOR was 16.7 months (95% CI, 5.3-NR) among all responders; the median DOR was not reached (95% CI, 16.7-NR) among responders who achieved a CR; and the median DOR was 1.4 months (95% CI, 1.1-2.2) among responders who achieved a best response of PR. Of the 104 patients who achieved CR, 65% had remission lasting at least 6 months and 62% had remission lasting at least 9 months.
“In TRANSCEND NHL 001, Breyanzi produced sustained responses in a significant proportion of patients with relapsed or refractory large B-cell lymphoma,” said Jeremy Abramson, MD, MMSc, director of the lymphoma program at Massachusetts General Hospital and principal investigator for TRANSCEND NHL 001. “TRANSCEND also demonstrated feasibility of outpatient administration, which is meaningful for patients, physicians and the healthcare system.”
As for safety, the most common nonlaboratory adverse reactions (incidence greater than or equal to 20%) with Breyanzi were fatigue, cytokine release syndrome, musculoskeletal pain, nausea, headache, encephalopathy, infections (pathogen unspecified), decreased appetite, diarrhea, hypotension, tachycardia, dizziness, cough, constipation, abdominal pain, vomiting, and edema.
Breyanzi carries a Boxed Warning regarding the risk for cytokine release syndrome and neurologic toxicities including fatal or life-threatening reactions. It is available only through a restricted program called the Breyanzi REMS.
Additionally, BMS is supporting the patient and physician treatment experience by providing a digital service platform called Cell Therapy 360, which optimizes access to relevant information, manufacturing updates, patient and caregiver support, and outpatient management resources.
Breyanzi is supplied in vials as separate frozen suspensions of each CD8 and CD4 component; each component is packed in a carton containing up to 4 vials, depending upon the concentration of the cryopreserved drug product CAR-positive vial T cells.
For more information visit breyanzi.com.
- FDA approves new treatment for adults with relapsed or refractory large-b-cell lymphoma. [press release]. Silver Spring, MD: US Food and Drug Administration; February 5, 2021.
- U.S. Food and Drug Administration approves Bristol Myers Squibb’s Breyanzi (lisocabtagene maraleucel), a new CAR T Cell therapy for adults with relapsed or refractory large b-cell lymphoma. [press release]. Princeton, NJ: Bristol Myers Squibb; February 5, 2021
- Breyanzi [package insert]. Princeton, NJ: Bristol Myers Squibb; 2021.