Approximately one-third of patients diagnosed with Hodgkin lymphoma presenting with Stage IV disease do not survive past 5 years. We present updated efficacy and safety analyses in high-risk patient subgroups, defined by Stage IV disease or International Prognostic Score (IPS) of 4-7, enrolled in the ECHELON-1 study that compared brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A + AVD) versus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as first-line therapy after a median follow-up of 37.1 months. Among patients treated with A + AVD (n = 664) or ABVD (n = 670), 64% had Stage IV disease and 26% had an IPS of 4-7. Patients with Stage IV disease treated with A + AVD showed consistent improvements in PFS at 3 years as assessed by investigator (hazard ratio [HR], 0.723; 95% confidence interval [CI], 0.537-0.973; p = 0.032). Similar improvements were seen in the subgroup of patients with IPS of 4-7 (HR, 0.588; 95% CI, 0.386-0.894; p = 0.012). The most common adverse events (AEs) in A + AVD-treated versus ABVD-treated patients with Stage IV disease were peripheral neuropathy (67% vs. 40%) and neutropenia (71% vs. 55%); in patients with IPS of 4-7, the most common AEs were peripheral neuropathy (69% vs. 45%), neutropenia (66% vs. 55%), and febrile neutropenia (23% vs. 9%), respectively. Patients in high-risk subgroups did not experience greater AE incidence or severity than patients in the total population. This updated analysis of ECHELON-1 shows a favorable benefit-risk balance in high-risk patients.

1st Faculty of Medicine General University Hospital Prague Czech Republic

Centre for Lymphoid Cancer BC Cancer Vancouver British Columbia Canada

CHU de Grenoble Grenoble France

Clinical Hematology Department Institut Català d'Oncologia Hospitalet and Institut d'Investigacions Biomèdiques de Bellvitge Universitat de Barcelona Barcelona Spain

Cross Cancer Institute University of Alberta Edmonton Alberta Canada

Dana Farber Cancer Institute Boston Massachusetts USA

Department of Haematology and Phase 1 Unit Rigshospitalet Copenhagen Denmark

Department of Hematology and Oncology Osaka University Osaka Japan

Department of Hematology Faculty of Medicine University of Debrecen Debrecen Hungary

Manchester Academic Health Science Centre University of Manchester and the Christie NHS Foundation Trust Manchester UK

Massachusetts General Hospital Cancer Center Boston Massachusetts USA

Mayo Clinic Rochester Minnesota USA

Millennium Pharmaceuticals Inc Cambridge Massachusetts USA

Research and Innovation Department Centre Antoine Lacassagne Nice France

Seattle Genetics Bothell Washington USA

University Hospital and Faculty of Medicine Hradec Králové Czech Republic

Wilmot Cancer Institute University of Rochester Medical Center Rochester New York USA

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