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.

FDA Approves Lisocabtagene Maraleucel for Second-Line Treatment of Large B-Cell 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.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.

For assistance with single-patient investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.