HL-507 First-Line Brentuximab Vedotin Plus Chemotherapy Improves Overall Survival in Patients With Stage III/IV Classical Hodgkin Lymphoma: An Updated Analysis of ECHELON-1

Context: Overall survival (OS) benefit from upfront treatment with new over existing approaches has never been shown in first-line (1L) classical Hodgkin lymphoma (cHL). With newer therapies for relapsed/refractory disease, demonstrating improved OS with 1L therapy has been challenging. In ECHELON-1 (NCT01712490), 5-year follow-up analyses supported a long-term progression-free survival (PFS) benefit with 1L brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) vs doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in patients with stage Ill/IV cHL. A+AVD had a manageable long-term safety profile, with fewer second malignancies and more pregnancies reported vs ABVD (Connors et al, NEJM 2018; Straus et al, Lancet Haematol 2021). We report a prespecified OS analysis after approximately 6 years' follow-up. Interventions: Patients were randomized 1:1 to receive up to 6 cycles of A+AVD (n=664) or ABVD (n=670) on day 1 and 15, every 28 days. Main Outcomes Measures: OS was the key prespecified secondary endpoint. Results: At a median follow-up of 73 months, 39 and 64 deaths occurred in A+AVD and ABVD arms, respectively; OS significantly favored A+AVD (hazard ratio [HR] 0.590; 95% confidence interval [Cl] 0.396–0.879; p = 0.009). Estimated 6-year OS rates (95% Cl) were 93.9% (91.6–95.5) vs 89.4% (86.6–91.7) with A+AVD vs ABVD, respectively, with a consistently higher OS across prespecified subgroups. The 6-year PFS estimate was 82.3% (79.1–85.0) vs 74.5% (70.8–77.7) with A+AVD vs ABVD, respectively (HR 0.678 [95% Cl 0.532–0.863]). Overall, A+AVD and ABVD had comparable long-term safety profiles. By the last follow-up, 86% (379/443) of treatment-related peripheral neuropathy cases in the A+AVD arm and 87% (249/286) in the ABVD arm either completely resolved (72% vs 79%, respectively) or were improving (14% vs 8%, respectively). Fewer second malignancies (23 vs 32) and more pregnancies (49 vs 28) were reported in the A+AVD vs ABVD arm, respectively. No new safety signals were identified. Conclusions: In this updated analysis, A+AVD treatment resulted in a 41% reduction in risk of death vs ABVD, with a manageable safety profile. These outcomes are important in advancing treatment of patients with previously untreated stage Ill/IV cHL.