14.8 vs 7.8 months median overall survival, brentuximab vedotin combination vs placebo, in DLBCL

In the Phase 3 ECHELON-3 trial of 230 randomized participants with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), median overall survival was 14.8 months (95% confidence interval 10.3 to 21.5) with brentuximab vedotin plus lenalidomide and rituximab and 7.8 months (95% confidence interval 5.7 to 11.7) with placebo plus lenalidomide and rituximab, the study record shows. The record from Seagen, a wholly owned subsidiary of Pfizer, now holds the primary outcome and the response, progression and safety measures for a combination that the ADCETRIS label already lists.

Why it matters

The DailyMed label for ADCETRIS (brentuximab vedotin), version published Nov 17, 2025, lists the combination with lenalidomide and a rituximab product for adult patients with relapsed or refractory large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) NOS. The label limits that use to patients after two or more lines of systemic therapy who are not eligible for auto-HSCT or chimeric antigen receptor (CAR) T-cell therapy. The record's summary says the trial studies whether brentuximab vedotin plus two drugs works better to treat this type of cancer than the two drugs alone. The record also cites a 2025 J Clin Oncol article titled "Brentuximab Vedotin Combination for Relapsed Diffuse Large B-Cell Lymphoma".

Survival and response

The study record shows results first posted on October 21, 2026. The results are based on the primary completion date of the study, and the record says only the secondary outcome measures with analyses complete at that date are reported. Overall survival is the primary outcome. Response measures are as assessed by the investigator per Lugano 2014.

Median overall survival: 14.8 months (95% confidence interval 10.3 to 21.5) for brentuximab vedotin + lenalidomide + rituximab, 112 participants; 7.8 months (5.7 to 11.7) for placebo + lenalidomide + rituximab, 118 participants. Hazard ratio 0.68 (95% confidence interval 0.501 to 0.922), p =0.0127, log rank.
Progression-Free Survival (PFS), median: 4.2 months (3.0 to 7.1) and 2.6 months (1.4 to 3.1). Hazard ratio 0.607 (0.447 to 0.824), p =0.0012.
Objective response rate: 64.3 percent (54.7 to 73.1) and 41.5 percent (32.5 to 51.0), p =0.0006, Cochran-Mantel-Haenszel.
Complete response rate: 41.1 percent (31.9 to 50.8) and 18.6 percent (12.1 to 26.9).
Duration of response, median: 8.3 months (4.1 to 15.3) among 72 participants evaluable, and 4.1 months (2.8 to 8.1) among 49.

The record defines the objective response rate as the percentage of participants with a response assessment of complete response or partial response per the Lugano 2014 response criteria as assessed by the investigator. The record states that overall survival was estimated using the Kaplan-Meier method, with a time frame of maximum up to 50 months.

Study design and participants

ECHELON-3 is a randomized, double-blind, placebo-controlled, active-comparator, multicenter Phase 3 study. Participants received brentuximab vedotin 1.2 mg/kg or placebo by IV infusion on Day 1 of each cycle, and each cycle was 21 days. All participants received lenalidomide 20 mg by mouth daily and rituximab 375 milligrams per square meter by IV infusion on Cycle 1 Day 1. From Cycle 2, rituximab and hyaluronidase human 1400 mg by subcutaneous injection was permitted.

The record says 240 participants were enrolled. Of these, 10 participants were part of the Safety Run-In population before random assignment and are excluded from the Intent-to-Treat (ITT) population, so the results cover 230. Participants had relapsed or refractory DLBCL after 2 or more lines of prior systemic therapy and were ineligible for HSCT or CAR-T, according to the investigator. The mean age was 69.2 years in the brentuximab vedotin arm and 65.8 years in the placebo arm. The record lists the estimated study completion date as December 31, 2026.

Safety

The safety analysis set included 112 participants on brentuximab vedotin + lenalidomide + rituximab and 116 on placebo + lenalidomide + rituximab. The record counts participants with at least one event.

Treatment Emergent Adverse Events (TEAEs): 109 of 112 and 113 of 116.
Treatment Emergent Serious Adverse Events (TESAEs): 73 of 112 and 59 of 116.
Maximum severity grade 3: 45 and 51 participants. Grade 4: 38 and 31. Grade 5: 16 and 9.

The participant flow lists death as the reason 73 of 112 and 83 of 118 participants did not complete the study.