Lisocabtagene maraleucel, sold under the brand name Breyanzi, is a cell-based gene therapy used to treat large B-cell lymphoma.Side effects include hypersensitivity reactions, serious infections, low blood cell counts, and a weakened immune system. The most common side effects include decreases in neutrophils (a type of white blood cell that fights infections), in red blood cells or in blood platelets (components that help the blood to clot), as well as cytokine release syndrome (a potentially life-threatening condition that can cause fever, vomiting, shortness of breath, pain and low blood pressure) and tiredness.Lisocabtagene maraleucel, a chimeric antigen receptor (CAR) T cell (CAR-T) therapy, is the third gene therapy approved by the U.S. Food and Drug Administration (FDA) for certain types of non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL). Lisocabtagene maraleucel was approved for medical use in the United States in February 2021.
The FDA granted approval of Breyanzi to Juno Therapeutics Inc., a Bristol-Myers Squibb Company.Efficacy was evaluated in TRANSFORM (NCT03575351), a randomized, open-label, multicenter trial in adults with primary refractory LBCL or relapse within twelve months of achieving complete response (CR) to first-line therapy. Participants had not yet received treatment for relapsed or refractory lymphoma and were potential candidates for autologous HSCT. A total of 184 participants were randomized 1:1 to receive a single infusion of lisocabtagene maraleucel following fludarabine and cyclophosphamide lymphodepleting chemotherapy or to receive second-line standard therapy, consisting of three cycles of chemoimmunotherapy followed by high-dose therapy and autologous HSCT in participants who attained CR or partial response (PR).Efficacy was also evaluated in PILOT (NCT03483103), a single-arm, open-label, multicenter trial in transplant-ineligible patients with relapsed or refractory LBCL after one line of chemoimmunotherapy. The study enrolled participants who were ineligible for high-dose therapy and HSCT due to organ function or age, but who had adequate organ function for CAR-T cell therapy. Efficacy was based on CR rate and duration of response (DOR) as determined by an IRC. Of 74 participants who underwent leukapheresis (median age, 73 years), 61 (82%) received lisocabtagene maraleucel of whom 54% (95% CI: 41, 67) achieved CR. The median DOR was not reached (95% CI: 11.2 months, not reached) in participants who achieved CR and 2.1 months (95% CI: 1.4, 2.3) in participants with a best response of PR. Among all leukapheresed participants, the CR rate was 46% (95% CI: 34, 58).