Based on results from the phase 3 TRANSFORM trial, the FDA has approved lisocabtagene maraleucel for the second-line treatment of relapsed/refractory large B-cell lymphoma.
The FDA has approved lisocabtagene maraleucel (liso-cel; Breyanzi) as treatment for relapsed/refractory large B-cell lymphoma (LBCL) following 1 prior line of therapy, according to Bristol Myers Squibb.1
The newly approved indication extends to patients with diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from indolent lymphoma; high-grade B-cell lymphoma; primary mediastinal LBCL; and grade 3B follicular lymphoma. Disease could be refractory to or relapsing within 12 months of frontline chemoimmunotherapy or relapsed/refractory to chemoimmunotherapy and ineligible for hematopoietic stem cell transplant.
“Breyanzi represents a remarkable advance over a nearly 30-year standard of care, providing significantly improved efficacy with a well-established safety profile,” Manali Kamdar, MD, associate professor and clinical director of Lymphoma Services, Division of Hematology, Hematologic Malignancies and Stem Cell Transplantation at the University of Colorado Cancer Center, said in a press release. “This important milestone reinforces the benefit of offering a CAR T-cell therapy option to patients earlier in their treatment journey and it’s critical that we begin the work to implement this therapy into standard practice as a second-line treatment in order to help improve outcomes for more patients.”
The approval is based on the phase 3 TRANSFORM trial (NCT03575351),2 in which patients treated with liso-cel had statistically significant improvement in event-free survival (EFS) compared with the standard of care (SOC). The median EFS in the liso-cel arm (n = 92) was 10.1 months (95% CI, 6.1–not reached [NR]) vs 2.3 months (95% CI, 2.2-4.3) in the SOC arm (n = 92; HR, 0.349; 95% CI, 0.229-0.530; P <.0001). At 6 months, the EFS rates were 63.3% (95% CI, 52.0%-74.7%) and 33.4% (95% CI, 23.0%-43.8%), and at 12-months were 44.5% (95% CI, 29.4%-59.6%) and 23.7% (95% CI, 13.4%-34.1%) in the liso-cel and SOC arms, respectively.
The objective response rate in the liso-cel arm was 86% (95% CI, 77.0%-92.3%) vs 48% (95% CI, 37.3%-58.5%) in the SOC arm. Those treated with liso-cel had a complete response rate of 66% (95% CI, 55.7%-75.8%; P <.0001) vs 39% (95% CI, 13.4%-34.1%) in the SOC arm (P <.0001).
The median progression-free survival (PFS) was 14.8 months (95% CI, 6.6-NR) in the liso-cel arm compared with 5.7 months (95% CI, 3.9-9.4) in the SOC arm (HR, 0.406; 95% CI, 0.250-0.659; P = .0001).
Grade 3 or higher treatment-emergent adverse effects (TEAEs) in the liso-cel arm included neutropenia (80%), anemia (49%), thrombocytopenia (49%), and lymphopenia (25%). In 48% of patients in both arms, serious TEAEs were identified. Any-grade cytokine release syndrome was observed in 49 patients in the liso-cel arm, with a median time to onset of 5 days and a median time to resolution of 4 days.
Of 232 patients who were screened, 184 received leukapheresis and were randomized 1:1. At the time of data reporting, 78 patients were continuing treatment in the liso-cel arm vs 32 in the SOC. Fifty patients crossed over from the SOC arm to receive liso-cel, with 46 ultimately receiving CAR T-cell therapy as their third-line treatment.
At data cut-off, the median follow-up for the liso-cel and SOC cohorts was 6.2 months. Patients included in the analysis underwent leukapheresis and then randomization, with the liso-cel arm receiving 100 x 106 CAR T cells and the SOC arm having 3 cycles of salvage therapy then high-dose chemotherapy plus autologous stem cell transplantation.