In an interim analysis of a phase III trial (ECHELON-3) reported in the Journal of Clinical Oncology, Bartlett et al found that the addition of brentuximab vedotin (BV) to lenalidomide and rituximab improved overall survival in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
Study Details
In the double-blind trial, 230 patients from sites in 14 countries were randomly assigned between April 2021 and November 2023 to receive BV plus lenalidomide/rituximab (n = 112) or placebo plus lenalidomide/rituximab (n = 118). Patients received BV at 1.2 mg/kg or placebo intravenously every 3 weeks, lenalidomide at 20 mg once daily, and rituximab at 375 mg/m2 every 3 weeks. The median number of prior systemic treatments was three (range = 2–8) in the BV group and three (range = 2–7) in the control group. The primary endpoint was overall survival. A prespecified interim analysis was performed after 134 overall survival events, with P = .0232 as the efficacy boundary.
Key Findings
Median follow-up for overall survival was 15.5 months (95% confidence interval [CI] = 12.2–18.1 months) in the BV group and 18.9 months (95% CI = 12.2–23.2 months) in the control group. Median overall survival was 13.8 months (95% CI = 10.3–18.8 months) in the BV group vs 8.5 months (95% CI = 5.4–11.7 months) in the control group (hazard ratio [HR] = 0.63, 95% CI = 0.45–0.89, P = .009).
Median progression-free survival was 4.2 months vs 2.6 months (HR = 0.53, 95% CI = 0.38–0.73, P < .001). Objective response rate was 64% vs 42% (P < .001), with a complete response rate of 40% vs 19%.
Grade ≥ 3 adverse events occurred in 88% of the BV group vs 77% of the control group. The most common were neutropenia (43%), thrombocytopenia (25%), anemia (22%), pneumonia (11%), and febrile neutropenia (9%) in the BV group and neutropenia (28%), anemia (21%), thrombocytopenia (19%), and febrile neutropenia (9%) in the control group. Adverse events led to death in 12% vs 8% of patients, most commonly COVID-19–related events (4% vs 3%).
The investigators concluded: “BV [plus lenalidomide plus rituximab] demonstrated a statistically significant survival benefit with a manageable safety profile in heavily pretreated patients with [relapsed/refractory] DLBCL.”
Nancy L. Bartlett, MD, of Washington University School of Medicine, Siteman Cancer Center, St Louis, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by Seagen Inc, which was acquired by Pfizer in December 2023. For full disclosures of the study authors, visit ascopubs.org.
