FDA Approves Breyanzi for Adults with Relapsed, Refractory Large B-cell Lymphoma

The FDA has approved lisocabtagene maraleucel (Breyanzi, Bristol Myers Squibb) as a new chimeric antigen receptor (CAR) T-cell therapy for adults with relapsed or refractory large B-cell lymphoma (R/R LBCL).

Breyanzi is a CD19-directed CAR T-cell therapy indicated for adults with R/R LBCL who have received 2 or more lines of systemic therapy, including diffuse LBCL not otherwise specified, high-grade B-cell lymphoma, primary mediastinal LBCL, and follicular lymphoma grade 3B. It is not indicated for the treatment of patients with primary central nervous system lymphoma.

The treatment is administered as a defined composition to reduce variability of the CD8 and CD4 component dose and is enhanced by the 4-1BB signaling. According to a press release, it may offer a potentially definitive treatment with a single dose containing 50 to 100 x 10⁶ CAR-positive viable T cells.

“Breyanzi, a CAR T-cell therapy, will have an important role in clinical practice, offering people living with relapsed or refractory large B-cell lymphoma the chance for sustained response with an individualized treatment experience,” said Samit Hirawat, MD, chief medical officer at Bristol Myers Squibb, in a press release.

The approval is based on data from the TRANSCEND NHL 001 trial, in which 268 patients with R/R LBCL received Breyanzi. The patient population included those with a broad range of histologies and high-risk disease, and Breyanzi was administered in both inpatient and outpatient settings.

According to the study results, 192 patients were treated with Breyanzi at a dose of 50 to 110 x 10⁶ CAR-positive viable T cells and were evaluated for efficacy. Of those patients, 73% achieved a response, including 54% who had minimal or no detectable lymphoma remaining following treatment and 19% who achieved a partial response.

The median duration of response was 16.7 months in all responders, and patients who achieved a complete response did not reach a median duration of response. For patients with a best response of partial response, the median duration was 1.4 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, principal investigator and director of the lymphoma program at Massachusetts General Hospital, in the press release. “TRANSCEND also demonstrated feasibility of outpatient administration, which is meaningful for patients, physicians, and the health care system. With this approval, we now have an important new treatment option for patients with relapsed or refractory large B-cell lymphoma who have undergone at least 2 prior lines of systemic therapy.”

Furthermore, 268 patients were evaluated for safety. Any grade of cytokine release syndrome (CRS) occurred in 46% of patients, whereas grade 3 or higher CRS occurred in 4%. One patient had fatal CRS and 2 had ongoing CRS at the time of death. The most common manifestations included fever, hypotension, tachycardia, chills, and hypoxia, whereas the median duration of CRS was 5 days and the median time to onset was 5 days.

Any grade of neurologic toxicities occurred in 35% of patients receiving Breyanzi whereas grade 3 or higher toxicities occurred in 12%. Three patients had fatal neurologic toxicity and 7 had ongoing neurologic toxicity at the time of death. The most common toxicities included encephalopathy, tremor, aphasia, delirium, headache, ataxia, and dizziness. Neurologic toxicities resolved in 81 of 95 patients, with a median duration of 12 days.

Finally, serious adverse events (AEs) occurred in 46% of patients. The most common nonlaboratory, serious AEs were CRS, encephalopathy, sepsis, febrile neutropenia, aphasia, pneumonia, fever, hypotension, dizziness, and delirium. Fatal AEs occurred in 4% of patients.

The most common nonlaboratory AEs of any grade were fatigue, CRS, musculoskeletal pain, nausea, headache, encephalopathy, infections, decreased appetite, diarrhea, hypotension, tachycardia, dizziness, cough, constipation, abdominal pain, vomiting, and edema.

“People battling relapsed or refractory large B-cell lymphoma continue to face a challenging treatment journey, both physically and emotionally,” said Meghan Gutierrez, chief executive officer of the Lymphoma Research Foundation, in a press release. “Breyanzi is an innovative treatment that offers a new option for patients, and another reason for this community to maintain hope for the future.”

REFERENCE

US 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 [news release]. Bristol Myers Squibb; February 5, 2021. https://news.bms.com/news/details/2021/U.S.-Food-and-Drug-Administration-Approves-Bristol-Myers-Squibbs-Breyanzi-lisocabtagene-maraleucel-a-New-CAR-T-Cell-Therapy-for-Adults-with-Relapsed-or-Refractory-Large-B-cell-Lymphoma/default.aspx. Accessed February 8, 2021.