ECHELON-3 trial: Brentuximab vedotin plus lenalidomide and rituximab for patients with R/R DLBCL

The phase III ECHELON-3 trial (NCT04404283) is evaluating the efficacy and safety of brentuximab vedotin (BV) plus lenalidomide (Len) and rituximab (R) vs placebo (Pbo)+Len+R in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who have received ≥2 prior lines of systemic therapy.¹ A prespecified interim analysis has been published in the Journal of Clinical Oncology, by Bartlett et al.¹ Here, we present a visual abstract summarizing these results.  

Key findings from the ECHELON-3 trial¹

• The median duration of follow-up for overall survival was 15.5 months (95% confidence interval [CI], 12.2–18.1) in the BV+Len+R arm and 18.9 months (95% CI, 12.2–23.2) in the Pbo+Len+R arm. The risk of death was reduced by 37% with BV+Len+R vs Pbo+Len+R (stratified hazard ratio [HR], 0.63; 95% CI, 0.45–0.89; two-sided p = 0.009); the median overall survival was 13.8 months (95% CI, 10.3–18.8) and 8.5 months (95% CI, 5.4–11.7), respectively.
• BV+Len+R significantly reduced the risk of disease progression or death by 47% compared with Pbo+Len+R (HR, 0.53; 95% CI, 0.38–0.73; two-sided p < 0.001), leading to a median progression-free survival of 4.2 months (95% CI, 2.9–7.1) and 2.6 months (95% CI, 1.4–3.1), respectively.
• ORR was higher in the BV+Len+R arm vs Pbo+Len+R arm (64% [95% CI, 55–73] vs 42% [95% CI, 33–51]; two-sided p < 0.001).
• The regimen was effective across various subgroups, including those aged ≥65 years, those with an International Prognostic Index score ≥3, and those who had previously undergone CAR T-cell therapy.
• BV+Len+R resulted in a survival benefit regardless of CD30 expression.
• The median duration of response was 8.3 months (95% CI, 4.2–15.3) with BV+Len+R and 3 months (95% CI, 2.8–5.4) with Pbo+Len+R.
• Treatment-emergent adverse events occurred in 97% of patients in both arms, with the most common being neutropenia, thrombocytopenia, diarrhea, and anemia.
• The safety profile was manageable and consistent with the known profiles of the individual agents.

Overall, the results from the ECHELON-3 trial showed that treatment with BV+Len+R led to a statistically significant survival benefit with a manageable safety profile in heavily pretreated patients with R/R DLBCL.¹ The survival benefit was observed across most subgroups, including high-risk subgroups. The results suggest that BV+Len+R could be a viable therapeutic option for the treatment of patients DLBCL in the third-line or later, particularly those who cannot receive CAR T-cell therapy or bispecific antibodies or have R/R disease after these treatments.¹

This educational resource is independently supported by Pfizer. All content was developed by SES in collaboration with an expert steering committee; funders were allowed no influence on the content of this resource.