Brentuximab vedotin regimen extends OS in heavily pretreated DLBCL
Key takeaways:
- The addition of brentuximab vedotin to lenalidomide and rituximab improved survival for certain patients with DLBCL.
- A similar percentage of patients in each arm experienced treatment-emergent adverse events.
The addition of brentuximab vedotin to lenalidomide and rituximab extended survival among heavily pretreated patients with relapsed or refractory diffuse large B-cell lymphoma.
The combination also exhibited a manageable safety profile, according to investigators.
“ECHELON-3 is the first randomized controlled study to demonstrate survival benefit in patients with relapsed or refractory diffuse large B-cell lymphoma in the third-line or later setting. Efficacy was observed across high-risk subgroups,” Nancy L. Bartlett, MD, Koman professor of medical oncology at Washington University School of Medicine in St. Louis, and colleagues wrote. “ECHELON-3 could potentially affect the treatment landscape for relapsed or refractory diffuse large B-cell lymphoma by supporting the use of brentuximab vedotin plus lenalidomide plus rituximab in this patient population.”
Brentuximab vedotin (Adcetris, Pfizer) as monotherapy or in combination with either lenalidomide or rituximab (Rituxan; Genentech, Biogen) has shown encouraging efficacy with a favorable safety profile for patients with relapsed or refractory DLBCL, according to study background.
Bartlett and colleagues conducted the randomized phase 3 ECHELON-3 trial to compare lenalidomide and rituximab plus brentuximab vedotin or placebo.
The trial included 230 patients who received at least two previous lines of systemic therapy, were considered ineligible for hematopoietic stem cell transplantation or chimeric antigen receptor T-cell therapy, and had an ECOG performance status of 2 or lower.
Researchers randomly assigned 112 patients (median age, 74 years; 54% men) to 1.2 mg/kg brentuximab vedotin via IV once every 3 weeks, 20 mg oral lenalidomide daily and 375 mg/m2 rituximab once every 3 weeks. The other 118 patients (median age, 70 years; 59% men) received placebo plus lenalidomide and rituximab. After the first cycle patients could receive subcutaneous rituximab dosed at 1,400 mg.
OS served as the primary endpoint. Investigator-assessed PFS and objective response rate served as secondary endpoints.
After median follow-up of 16.4 months, patients assigned brentuximab vedotin achieved longer median OS (13.8 months vs. 8.5 months; HR = 0.63; 95% CI, 0.45-0.89) and PFS (4.2 months vs. 2.6 months; HR = 0.53; 95% CI, 0.38-0.73).
Researchers also observed a higher ORR (64% vs 42%) and complete response rate (40% vs. 19%) in the brentuximab vedotin cohort.
Treatment-emergent adverse events occurred among 97% of patients in both arms. At least 20% of patients in each treatment arm developed neutropenia, thrombocytopenia, diarrhea or anemia.
Researchers acknowledged study limitations, including the fact an independent data monitoring committee evaluated OS but not the secondary endpoints, a short follow-up period, and a lack of detailed data regarding efficacy data as it pertained to previous number of lines of therapy.
In an accompanying editorial, Jennifer L. Crombie, MD, medical oncologist at Dana-Farber Cancer Institute, and Ann S. LaCasce, MD, MMSc, associate professor of medicine at Harvard Medical School and director of the Dana-Farber/Mass General Brigham fellowship in hematology/oncology, lauded the researchers for conducting the ECHELON-3 trial.
However, they raised questions about where the combination of lenalidomide, rituximab and brentuximab vedotin regimen fits into the treatment landscape for relapsed or refractory DLBCL given the availability of other therapeutic options.
“A number of factors aside from the efficacy of the regimen contribute to the outcome,” Crombie and LaCasce wrote. “First, the comparator arm — lenalidomide and rituximab — sets a low bar for comparison. Lenalidomide and rituximab is not an approved option for patients with relapsed or refractory DLBCL, and previous studies of the combination in relapsed or refractory DLBCL have demonstrated poor outcomes. Thus, the median PFS of placebo plus lenalidomide plus rituximab of only 2.6 months is not surprising. Second, the median follow-up of the experimental arm was 3 months shorter than the control arm and might have contributed to the observed difference in PFS.”
The “true value” of the three-agent combination may only become clear after longer follow-up of ECHELON-3 and availability of real-world data, they added.
“In addition, cost-effectiveness studies should be performed given the price of brentuximab vedotin and lenalidomide, which may be associated with high out-of-pocket expense,” they wrote. “Overall, where [this regimen] will fit within the evolving treatment landscape of relapsed or refractory DLBCL remains to be seen.”
References:
- Bartlett NL, et al. J Clin Oncol. 2025;doi:10.1200/JCO-24-02242.
- Crombie JL, et al. J Clin Oncol. 2025;doi:10.1200/JCO-24-02483.
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