FDA Approves New CAR T-Cell Therapy for B-Cell Lymphoma

Breyanzi Provides Sustained Response and Personalized Treatment Experience

The FDA has approved a new chimeric antigen receptor (CAR) T-cell therapy, Breyanzi (lisocabtagene maraleucel or liso-cel), for the treatment of adults with large B-cell lymphoma who have not responded to — or who have relapsed after — two previous treatments.

Bristol Myers Squibb’s Breyanzi is a customized treatment created using a patient's own T cells, a type of white blood cell, to help fight lymphoma cells. The patient's T cells are collected and genetically modified to include a new gene that targets and destroys cancer cells while leaving healthy cells alone. Once the cells are modified, they are infused back into the patient. Breyanzi engineers the T cells to seek a protein called CD19. This new therapy offers a 24-day target turnaround time and can be administered in both inpatient and outpatient settings.

“[This] approval represents another milestone in the rapidly progressing field of gene therapy by providing an additional treatment option for adults with certain types of cancer affecting the blood, bone marrow and lymph nodes,” said Dr. Peter Marks, director of the FDA's Center for Biologics Evaluation and Research, in a Feb. 5 FDA press release. “Gene and cell therapies have evolved from promising concepts to practical cancer treatment regimens.”

Clinical Trial Leads to FDA Approval

The FDA based its approval of Breyanzi on data from the TRANSCEND NHL 001 trial of 268 patients with relapsed or refractory large B-cell lymphoma. In the study, 192 patients were treated with Breyanzi. Of these patients, 73% achieved a response, including 54% who had minimal or no detectable lymphoma remaining following treatment (complete remission, or CR).

Of 104 patients treated with Breyanzi who achieved a best overall response of CR, 65% had remission lasting at least six months and 62% had remission lasting at least nine months.

“In TRANSCEND NHL 001, Breyanzi produced sustained responses in a significant proportion of patients with relapsed or refractory large B-cell lymphoma,” said Dr. Jeremy Abramson, director of the lymphoma program at Massachusetts General Hospital and principal investigator for TRANSCEND NHL 001, in a Bristol Myers Squibb press release. “TRANSCEND also demonstrated feasibility of outpatient administration, which is meaningful for patients, physicians and the healthcare system.”

Side Effects of Breyanzi Lymphoma Treatment

Treatment with Breyanzi has the potential to cause severe side effects. The labeling carries a boxed warning for cytokine release syndrome (CRS), a systemic response to the activation and proliferation of CAR-T cells, causing high fever and flu-like symptoms and neurologic toxicities. Both CRS and neurological events can be life-threatening, according to the FDA release.

Because of the risk of CRS and neurologic toxicities, Breyanzi is being approved with a risk evaluation and mitigation strategy (REMS), which includes elements to assure safe use (ETASU), such as requiring healthcare facilities that dispense Breyanzi to be specially certified. 

The REMS program specifies that patients be informed of the signs and symptoms of CRS and neurological toxicities following infusion — and of the importance of promptly returning to the treatment site if they develop a fever or other adverse reactions.

CAR T-Cell Therapies Give Patients Hope for the Future

Breyanzi is the fourth CAR T-cell therapy approved by the FDA, and the third for large B-cell lymphoma. The FDA previously approved tisagenleleucel (Kymriah, Novartis) for the treatment of certain patients with diffuse large B-cell lymphoma or B-cell acute lymphoblastic leukemia; axicabtagene ciloleucel (Yescarta, Kite Pharma/Gilead) for the treatment of adults with relapsed or refractory large B-cell lymphoma; and brexucabtagene autoleucel (Tecartus, Kite Pharma/Gilead) for the treatment of adults with relapsed or refractory mantle cell lymphoma.

“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, Lymphoma Research Foundation, in the Bristol Myers Squibb 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.”