Dr Nowakowski on the FDA Approval of Brentuximab Vedotin for R/R LBCL

"This treatment is important because it provides a new way of treating large [B-cell] lymphoma in the relapsed/refractory setting...The targeting of a different antigen with this different mode of action really provides a new opportunity for our patients." 

Grzegorz S. Nowakowsi, MD, a consultant in the Division of Hematology in the Department of Internal Medicine and the Enterprise Deputy Director of Clinical Research at the Mayo Clinic Comprehensive Cancer Center, discusses the significance of the FDA approval of brentuximab vedotin (Adcetris) in combination with lenalidomide (Revlimid) and rituximab (Rituxan)​ for patients with ​relapsed/refractory large B-cell lymphoma (LBCL).

On February 12, 2025, the FDA approved brentuximab vedotin plus lenalidomide and rituximab for the treatment of adult patients with relapsed/refractory LBCL—including diffuse LBCL (DLBCL) not otherwise specified, DLBCL arising from indolent lymphoma, or high-grade B-cell lymphoma—who have received at least 2 lines of systemic therapy and who are not eligible for autologous hematopoietic stem cell transplantation or CAR T-cell therapy. 

This regulatory decision was based on findings from the phase 3 ECHELON-3 trial (NCT04404283). In this study, patients who received the investigative combination (n = 112) had a median overall survival of 13.8 months (95% CI, 10.3-18.8) vs 8.5 months (95% CI, 5.4-11.7) with placebo plus lenalidomide and rituximab (n = 118; HR, 0.63; 95% CI, 0.45-0.89; P = .0085). Furthermore, the median progression-free survival was 4.2 months (95% CI, 2.9-7.1) in the brentuximab vedotin arm vs 2.6 months (95% CI, 1.4-3.1) in the placebo arm (HR, 0.53; 95% CI, 0.38-0.73; P < .0001). The overall response rate was 64.3% (95% CI, 54.7%-73.1%) with the experimental combination vs 41.5% (95% CI, 32.5%-51.0%) with control.

The relapsed/refractory DLBCL treatment paradigm has grown significantly over the past few years, Nowakowski says. Brentuximab vedotin is an important addition to the LBCL armamentarium because it uniquely targets CD30, whereas many other approved agents target CD19 or CD20, he explains.