• Stephen M Ansell, John Radford, Joseph M Connors, Monika Długosz-Danecka, Won-Seog Kim, Andrea Gallamini, Radhakrishnan Ramchandren, Jonathan W Friedberg, Ranjana Advani, Martin Hutchings, Andrew M Evens, Piotr Smolewski, Kerry J Savage, Nancy L Bartlett, Hyeon-Seok Eom, Jeremy S Abramson, Cassie Dong, Frank Campana, Keenan Fenton, Markus Puhlmann, David J Straus, and ECHELON-1 Study Group.
• From the Division of Hematology, Mayo Clinic, Rochester, MN (S.M.A.); the University of Manchester and the Christie NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom (J.R.); BC Cancer Centre for Lymphoid Cancer, Vancouver (J.M.C., K.J.S.); Maria Sklodowska-Curie National Research Institute of Oncology, Krakow (M.D.-D.), and the Department of Experimental Hematology, Medical University of Lodz, Lodz (P.S.) - both in Poland; the Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (W.-S.K.), and the Department of Hematology-Oncology, Center for Hematologic Malignancy, National Cancer Center, Goyang (H.-S.E.) - both in South Korea; Research and Innovation Department, Antoine-Lacassagne Cancer Center, Nice, France (A.G.); the University of Tennessee Graduate School of Medicine, Knoxville (R.R.); Wilmot Cancer Institute, University of Rochester, Rochester (J.W.F.), and the Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York (D.J.S.) - both in New York; the Department of Medicine, Division of Oncology, Stanford University, Stanford, CA (R.A.); the Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen (M.H.); the Division of Blood Disorders, Rutgers Cancer Institute of New Jersey, New Brunswick (A.M.E.); Washington University School of Medicine Siteman Cancer Center, St. Louis (N.L.B.); Massachusetts General Hospital, Boston (J.S.A.), and Takeda Development Center Americas, Lexington (C.D., F.C.) - both in Massachusetts; and Seagen, Bothell, WA (K.F., M.P.).
• N. Engl. J. Med. 2022 Jul 28; 387 (4): 310-320.

BackgroundFive-year follow-up in a trial involving patients with previously untreated stage III or IV classic Hodgkin's lymphoma showed long-term progression-free survival benefits with first-line therapy with brentuximab vedotin, a CD30-directed antibody-drug conjugate, plus doxorubicin, vinblastine, and dacarbazine (A+AVD), as compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). A planned interim analysis indicated a potential benefit with regard to overall survival; data from a median of 6 years of follow-up are now available.MethodsWe randomly assigned patients in a 1:1 ratio to receive up to six cycles of A+AVD or ABVD. The primary end point, modified progression-free survival, has been reported previously. The key secondary end point was overall survival in the intention-to-treat population. Safety was also assessed.ResultsA total of 664 patients were assigned to receive A+AVD and 670 to receive ABVD. At a median follow-up of 73.0 months, 39 patients in the A+AVD group and 64 in the ABVD group had died (hazard ratio, 0.59; 95% confidence interval [CI], 0.40 to 0.88; P = 0.009). The 6-year overall survival estimates were 93.9% (95% CI, 91.6 to 95.5) in the A+AVD group and 89.4% (95% CI, 86.6 to 91.7) in the ABVD group. Progression-free survival was longer with A+AVD than with ABVD (hazard ratio for disease progression or death, 0.68; 95% CI, 0.53 to 0.86). Fewer patients in the A+AVD group than in the ABVD group received subsequent therapy, including transplantation, and fewer second cancers were reported with A+AVD (in 23 vs. 32 patients). Primary prophylaxis with granulocyte colony-stimulating factor was recommended after an increased incidence of febrile neutropenia was observed with A+AVD. More patients had peripheral neuropathy with A+AVD than with ABVD, but most patients in the two groups had resolution or amelioration of the event by the last follow-up.ConclusionsPatients who received A+AVD for the treatment of stage III or IV Hodgkin's lymphoma had a survival advantage over those who received ABVD. (Funded by Takeda Development Center Americas and Seagen; ECHELON-1 ClinicalTrials.gov number, NCT01712490; EudraCT number, 2011-005450-60.).Copyright © 2022 Massachusetts Medical Society.

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