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

David Straus, John Radford, Joseph Connors, Won Seog Kim, Andrea Gallamini, Radhakrishnan Ramchandren, Jonathan Friedberg, Ranjana Advani, Martin Hutchings, Andrew Evens, Piotr Smolewski, Kerry Savage, Nancy Bartlett, Hyeon Seok Eom, Jeremy Abramson, Cassie Dong, Frank Campana, Keenan Fenton, Markus Puhlmann, Stephen Ansell

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)S350
JournalClinical Lymphoma, Myeloma and Leukemia
Volume22
DOIs
StatePublished - Oct 2022

Keywords

  • brentuximab vedotin
  • chemotherapy
  • classical Hodgkin lymphoma
  • ECHELON-1
  • HL
  • overall survival
  • Phase III

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