The Food and Drug Administration (FDA) has approved Breyanzi® (lisocabtagene maraleucel) for the treatment of adult patients with large B-cell lymphoma (LBCL), 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, who have:
- Refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy; or
- Refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age.
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 expanded approval was based on data from the randomized, open-label phase 3 TRANSFORM study (ClinicalTrials.gov Identifier: NCT03575351), which evaluated the efficacy and safety of Breyanzi in 184 adults with relapsed or refractory LBCL within 12 months of first-line chemoimmunotherapy. Patients were randomly assigned 1:1 to receive either a single infusion of Breyanzi or standard therapy consisting of 3 cycles of chemoimmunotherapy followed by high-dose therapy and autologous HSCT.
The primary endpoint was event-free survival (EFS) as determined by an independent review committee. Key secondary endpoints included complete response (CR) rate and progression-free survival (PFS).
Results showed that patients in the Breyanzi treatment arm achieved the following improvements vs those in the standard therapy arm, respectively:
- EFS: 10.1 months vs 2.3 months (hazard ratio [HR], 0.34; 95% CI, 0.22-0.52; P <.0001).
- CR rate: 66% (95% CI, 56-76) vs 39% (95% CI, 29-50) (P <.0001); median duration of CR was not reached (NR) in the Breyanzi arm (95% CI, 7.9-NR).
- Median PFS: 14.8 months vs 5.7 months (HR, 0.41; 95% CI, 0.25-0.66; P =.0001).
The efficacy of Breyanzi in the second-line setting was also supported by data from the single-arm, open-label, phase 2 PILOT trial (ClinicalTrials.gov Identifier: NCT03483103), which included 61 transplant-ineligible patients with relapsed or refractory LBCL after 1 line of chemoimmunotherapy. Findings showed an overall response rate of 80% (primary endpoint); 54% of patients achieved CR while 26% had a partial response. The median time to CR was 1 month (range, 0.8-6.9 months) and the median duration of response was 11.2 months (95% CI, 5.1-NR).
The most common nonlaboratory adverse reactions reported with Breyanzi were fatigue, cytokine release syndrome, musculoskeletal pain, and nausea. The most common grade 3 to 4 laboratory abnormalities included decreased lymphocyte count, decreased neutrophil count, decreased platelet count, and decreased hemoglobin.
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.
“Breyanzi represents a remarkable advance over a nearly 30-year standard of care, providing significantly improved efficacy with a well-established safety profile,” said Manali Kamdar, MD, lead investigator of the TRANSFORM study and Associate Professor, Clinical Director of Lymphoma Services, Division of Hematology, Hematologic Malignancies and Stem Cell Transplantation, University of Colorado Cancer Center. “This important milestone reinforces the benefit of offering a CAR T cell therapy option to patients earlier in their treatment journey and it’s critical that we begin the work to implement this therapy into standard practice as a second-line treatment in order to help improve outcomes for more patients.”
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.
- US FDA approves Bristol Myers Squibb’s CAR T cell therapy Breyanzi® for relapsed or refractory large B-cell lymphoma after one prior therapy. News release. Bristol Myers Squibb. June 24, 2022. Accessed June 27, 2022. https://www.businesswire.com/news/home/20220427005982/en/U.S.-FDA-Approves-Bristol-Myers-Squibb%E2%80%99s-CAR-T-Cell-Therapy-Breyanzi%C2%AE-for-Relapsed-or-Refractory-Large-B-cell-Lymphoma-After-One-Prior-Therapy
- Breyanzi. Package insert. Bristol Myers Squibb; 2022. Accessed June 27, 2022. https://packageinserts.bms.com/pi/pi_breyanzi.pdf
This article originally appeared on MPR