Second-Line Lisocabtagene Maraleucel vs Standard of Care for Relapsed/Refractory LBCL: TRANSFORM Trial

Lisocabtagene maraleucel (liso-cel) demonstrated significantly higher median event-free survival (EFS) than standard of care as a second-line therapy in patients with primary refractory or early (within 12 months after response to initial therapy) relapsed large B-cell lymphoma (LBCL), according to recent results from the TRANSFORM study.

The findings of this study, published in The Lancet, support liso-cel as a new second-line treatment recommendation in patients with early relapsed or refractory LBCL. These findings are from an interim analysis; the trial is ongoing.

“Patients with [LBCL] primary refractory to or relapsed within 12 months of first-line therapy are at high risk for poor outcomes with current standard of care, platinum-based salvage immunochemotherapy and autologous [hematopoietic] stem cell transplantation [autoHSCT],” wrote Manali Kamdar, MD, University of Colorado Cancer Center, Aurora, CO, and colleagues. “[Liso-cel], an autologous, CD19-directed chimeric antigen receptor (CAR) T-cell therapy, has previously demonstrated efficacy and manageable safety in third-line or later LBCL.”

This global, phase 3 study was conducted in 47 sites across the US, Europe, and Japan and enrolled adults of ages ranging from 18 to 75 years with an Eastern Cooperative Oncology Group performance status score of 1 or less, adequate organ function, PET-positive disease per Lugano 2014 criteria. These candidates for autoHSCT were randomly assigned in a 1:1 ratio using interactive response technology to either liso-cel (100 × 10⁶ CAR⁺ T cells intravenously) or standard of care treatment.

The primary end point was EFS, with response assessments by an independent review committee, per the Lugano 2014 criteria. Efficacy was assessed per intention-to-treat (ie, all randomly assigned patients) and safety in patients who received any treatment. Between October 23, 2018, and Dec 8, 2020, 232 patients were screened and 184 were assigned to the liso-cel (n = 92) or standard of care (n = 92) groups.

At the data cutoff for this interim analysis, March 8, 2021, the median follow-up was 6.2 months (interquartile range [IQR], 4.4 to 11.5). Median EFS was significantly improved in the liso-cel group (10.1 months [95% confidence interval [CI], 6.1 to not reached]) compared to the standard of care group (2.3 months [2.2 to 4.3]; stratified hazard ratio [HR], 0.35; 95% CI, 0.23 to 0.53; stratified Cox proportional hazards model one-sided P <.0001).

The most common grade 3 or worse adverse events were neutropenia (74 [80%] of 92 patients in the liso-cel group vs 46 [51%] of 91 patients in the standard of care group), anemia (45 [49%] vs 45 [49%]), thrombocytopenia (45 [49%] vs 58 [64%]), and prolonged cytopenia (40 [43%] vs three [3%]). Grade 3 cytokine release syndrome and neurological events, which are associated with CAR T-cell therapy, occurred in 1 (1%) and 4 (4%) of 92 patients in the liso-cel group, respectively. There were no grade 4 or 5 events.

“Serious treatment-emergent adverse events were reported in 44 (48%) patients in the liso-cel group and 44 (48%) in the standard-of-care group,” Kamdar and colleagues explained. “No new liso-cel safety concerns were identified in the second-line setting. There were no treatment-related deaths in the liso-cel group and one treatment-related death due to sepsis in the standard-of-care group.”

“These results support liso-cel as a new second-line treatment recommendation in patients with early relapsed or refractory LBCL,” the study authors concluded.

Source:

Kamdar M, Solomon SR, Arnason J, et al. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022;399(10343):2294-2308. doi:10.1016/S0140-6736(22)00662-6