On June 24, 2022, the U.S. Food and Drug Administration (FDA) approved lisocabtagene maraleucel (Breyanzi®) for adult patients with large B-cell lymphoma (LBCL) whose disease is refractory to first-line chemoimmunotherapy, have relapsed within a year of first-line chemoimmunotherapy, or are not eligible for hematopoietic stem cell transplantation (HSCT) after relapse. It is not for patients with primary central nervous system lymphoma.
Efficiency was evaluated with a randomized, open-label, multicenter trial in adult patients with primary refractory LBCL or relapse within 12 months of complete response (CR) to first-line therapy. Patients had not yet received treatment and were potential candidates for autologous HSCT. A total of 184 patients were randomized 1:1 to receive either a single infusion of lisocabtagene maraleucel following fludarabine and cyclophosphamide lymphodepleting chemotherapy or second-line standard therapy (i.e., three cycles of chemoimmunotherapy followed by high-dose therapy and autologous HSCT).
The primary efficacy measure was event-free survival (EFS) as determined by an independent review committee (IRC). EFS was significantly longer in the lisocabtagene maraleucel arm with a hazard ratio (HR) of 0.34 (95% CI = 0.22, 0.52; p < 0.0001). The estimated one-year EFS was 45% (95% CI = 29, 59) in the lisocabtagene maraleucel arm and 24% (95% CI = 14, 35) in the standard therapy arm. The estimated median EFS was 10.1 months (95% CI = 6.1, not evaluable) and 2.3 months (95% CI = 2.2, 4.3), respectively. Of patients randomized to receive standard therapy, 47% received autologous HSCT as planned; lack of response to chemotherapy was the most common reason for not receiving HSCT. The IRC-assessed progression-free survival was also significantly longer in the lisocabtagene maraleucel arm with a HR of 0.41 (95% CI = 0.25, 0.66; p < 0.0001).
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 patients who were ineligible for high-dose therapy and HSCT because organ function or age and 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 patients who underwent leukapheresis (median age = 73 years), 61 (82%) received lisocabtagene maraleucel; 54% of the patients (95% CI = 41, 67) achieved CR. The median DOR was not reached (95% CI = 11.2 months, not reached) in patients who achieved CR and 2.1 months (95% CI = 1.4, 2.3) in patients with a best response of PR. Among all leukapheresed patients, the CR rate was 46% (95% CI = 34, 58).
FDA approved lisocabtagene maraleucel with a Risk Evaluation and Mitigation Strategy because of the risk of fatal or life-threatening cytokine release syndrome (CRS) and neurologic toxicities. In studies of lisocabtagene maraleucel as second-line therapy for LBCL, CRS occurred in 45% of patients (1.3% were grade 3 or higher), and neurologic toxicities occurred in 27% of patients (7% were grade 3). Serious adverse reactions occurred in 33%–38% of patients.
The recommended lisocabtagene maraleucel dose for second-line therapy is 90 to 110 × 106 CAR-positive T cells with a 1:1 ratio of CD4 and CD8 components.
View the full prescribing information for lisocabtagene maraleucel.
This application was granted priority review, regenerative medicine advanced therapy designation, and breakthrough designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics. The application also received orphan drug designation.
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