Lisocabtagene maraleucel is approved by FDA for second-line treatment of large B-cell lymphoma

July 2022: Lisocabtagene maraleucel (Breyanzi, Juno Therapeutics, Inc.) has been approved by the Food and Drug Administration for adult patients with large B-cell lymphoma (LBCL) 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 Patients with primary central nervous system lymphoma cannot be treated with it.

In TRANSFORM (NCT03575351), a multicenter, randomised, open-label trial in adult patients with primary resistant LBCL or relapse within 12 months of attaining complete response (CR) to first-line therapy, efficacy was assessed. Patients who were potential candidates for autologous HSCT had not yet received treatment for relapsed or refractory lymphoma. 184 patients were divided into two groups: those receiving second-line standard treatment, which consists of three cycles of chemoimmunotherapy followed by high-dose therapy and autologous HSCT in patients who attained CR or partial response, and those receiving a single infusion of lisocabtagene maraleucel after fludarabine and cyclophosphamide lymphodepleting chemotherapy (PR).

Event-free survival (EFS) was the main efficacy metric, as decided by a separate review committee (IRC). With a hazard ratio (HR) of 0.34 (95 percent CI: 0.22, 0.52; p-value 0.0001), EFS was noticeably longer in the lisocabtagene maraleucel arm. The predicted 1-year EFS was 24 percent (95 percent CI: 14, 35) for conventional treatment and 45 percent (95 percent CI: 29, 59) for the lisocabtagene maraleucel arm. The estimated median EFS for each group was 2.3 months (95 percent CI: 2.2, 4.3) and 10.1 months (95 percent CI: 6.1, not evaluable). 47 percent of individuals who were randomly assigned to receive conventional therapy underwent autologous HSCT as scheduled; the most frequent reason for non-receipt of HSCT was chemotherapy failure. With an HR of 0.41, the lisocabtagene maraleucel arm also had significantly longer progression-free survival as determined by the IRC (95 percent CI: 0.25, 0.66; p-value 0.0001).

The effectiveness of PILOT (NCT03483103), a single-arm, open-label, multicenter trial for patients with relapsed or refractory LBCL following one line of chemoimmunotherapy, was also assessed. Patients who met the criteria for CAR-T cell therapy but were ineligible for high-dose therapy or HSCT due to age or organ function were enrolled in the trial. Effectiveness was evaluated using an IRC’s determination of the CR rate and DOR. 54 percent (95 percent confidence interval [CI]: 41, 67) of the 74 patients who underwent leukapheresis (median age, 73 years) and received lisocabtagene maraleucel were CR. The median DOR was not attained in individuals who received a CR and 2.1 months (95 percent CI: 1.4, 2.3) in patients who received a PR as their best response. The CR rate was 46% for all patients who had leukapheresis (95 percent CI: 34, 58).

Due to the possibility of fatal or seriously life-threatening cytokine release syndrome (CRS) and neurologic toxicities, the FDA approved lisocabtagene maraleucel with a Risk Evaluation and Mitigation Strategy. CRS occurred in 45% of patients (Grade 3 or above, 1.3%) in studies using lisocabtagene maraleucel as second-line therapy for LBCL, while neurologic toxicities occurred in 27% of patients (Grade 3, 7 percent ). 33 to 38 percent of patients experienced serious adverse effects.

For second-line therapy, 90 to 110 106 CAR-positive T cells with a 1:1 ratio of CD4 to CD8 components are the suggested lisocabtagene maraleucel dosage.

View full prescribing information for lisocabtagene maraleucel.