FDA Approves Brentuximab Vedotin Combo for Relapsed/Refractory Large B-Cell Lymphoma

Based on improved OS and PFS in the ECHELON-3 trial, the FDA approved the triplet combo for relapsed and refractory LBCL.

The FDA approved brentuximab vedotin (Adcetris) plus lenalidomide (Revlimid) and a rituximab (Rituxan) product to treat adults with relapsed or refractory large B-cell lymphoma (LBCL) after 2 or more lines of systemic therapy who are not eligible for autologous hematopoietic stem cell transplantation (auto-HSCT) or CAR T-cell therapy, according to an alert from the agency.¹

This approval includes the treatment of diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high-grade B-cell lymphoma (HGBL), and DLBCL arising from indolent lymphoma.

Findings from the ECHELON-3 (NCT04404283) trial supported this approval, according to the alert. This randomized, double-blind, placebo-controlled trial included 230 adults with relapsed or refractory LBCL who were ineligible for CAR T-cell therapy or auto-HSCT. Patients enrolled in the trial were randomized 1:1 to receive brentuximab vedotin plus lenalidomide and rituximab or placebo plus lenalidomide and rituximab. Treatment continued until disease progression or unacceptable toxicity.

The major efficacy outcome measure of this trial was overall survival (OS), with other outcomes of interest including objective response rate (ORR) per 2014 Lugano Criteria and progression-free survival (PFS).

The improvement regarding OS was statistically significant, with a median of 13.8 months (95% CI, 10.3-18.8) in the brentuximab vedotin arm compared with 8.5 months (95% CI, 5.4-11.7) in the placebo arm (HR = 0.63; 95% CI, 0.45-0.89; P = .0085). There were also statistically significant improvements in PFS and ORR. The median PFS was 4.2 months (95% CI, 2.9-7.1) with brentuximab vedotin compared with 2.6 months (95% CI, 1.4-3.1) with placebo (HR = 0.53; 95% CI, 0.38-0.73; P < .0001). Additionally, the ORR was 64.3% (95% CI, 54.7%-73.1%) in the brentuximab vedotin arm and 41.5% (95% CI, 32.5%-51.0%) in the placebo arm.

The most common adverse reactions, occurring in at least 20% of patients, excluding laboratory abnormalities in the brentuximab vedotin arm, were diarrhea, fatigue, rash, peripheral neuropathy, COVID-19 infection, and pneumonia, according to the agency. Grade 3 to 4 laboratory abnormalities, which were observed in more than 10% of patients, included decreased lymphocytes, decreased neutrophils, decreased hemoglobin, and decreased platelets.

Of note, peripheral neuropathy either developed or worsened in 27% of patients, which was predominantly sensory. This led to a dose reduction of brentuximab vedotin in 6% of patients and discontinuation in 4.5% of patients.

According to the FDA, the recommended dose of brentuximab vedotin is 1.2 mg/kg up to a maximum of 120 mg plus lenalidomide and rituximab, to be administered every 3 weeks until disease progression or unacceptable toxicity.

Additional Findings from ECHELON-3

Results from the ECHELON-3 trial were presented at the 2024 ASCO Annual Meeting.²

The median DOR in the overall population increased from 3.0 months (95% CI, 2.8-5.4) with the lenalidomide and rituximab regimen to 8.3 months (95% CI, 4.2-15.3) with the addition of brentuximab vedotin. Among those who achieved a complete response, the median duration of response was 18.9 months (95% CI, 11.1 months-not reached [NR]) in the brentuximab vedotin triplet arm and NR (95 % CI, 2.8-NR) in the lenalidomide and rituximab arm. The median time to complete response onset was 1.58 months (range, 1.2-7.3) and 1.61 months (range, 0.7-4.6) in these respective groups.

“ECHELON-3 [is] the first randomized, placebo-controlled phase 3 study to demonstrate an OS benefit in patients with relapsed/refractory DLBCL who have received more than 2 prior lines of systemic therapy,” lead study author Jeong A Kim, MD, of St Vincent’s Hospital, the Catholic University of Korea School of Medicine in Suwon, stated in an oral presentation of the data. “This triplet combination has the potential to address a high unmet need in patients with relapsed/refractory DLBCL, particularly those who are not able to receive CAR T-cell therapy or a bispecific antibody or who have a relapsed/refractory disease following this treatment.”

References

1. FDA approves brentuximab vedotin with lenalidomide and rituximab for relapsed or refractory large B-cell lymphoma. FDA. February 11, 2025. Accessed February 12, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-brentuximab-vedotin-lenalidomide-and-rituximab-relapsed-or-refractory-large-b-cell
2. Kim J, Hahn U, Kim WS, et al. Brentuximab vedotin in combination with lenalidomide and rituximab in patients with relapsed/refractory diffuse large B-cell lymphoma: Results from the phase 3 ECHELON-3 study. J Clin Oncol. 2024, 42(suppl 16):LBA7005.doi:10.1200/JCO.2024.42.16_suppl.LBA7005