• Sharon M Castellino, Qinglin Pei, Susan K Parsons, David Hodgson, Kathleen McCarten, Terzah Horton, Steve Cho, Yue Wu, Angela Punnett, Hema Dave, Tara O Henderson, Bradford S Hoppe, Anne-Marie Charpentier, Frank G Keller, and Kara M Kelly.
• From the Department of Pediatrics, Emory University School of Medicine (S.M.C., F.G.K.), and Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta (S.M.C., F.G.K.) - both in Atlanta; the Department of Biostatistics, Children's Oncology Group, Statistics and Data Center, University of Florida, Gainesville (Q.P., Y.W.), and the Department of Radiation Oncology, Mayo Clinic Florida, Jacksonville (B.S.H.); the Institute for Clinical Research and Health Policy Studies and Tufts Cancer Center, Tufts Medical Center, Boston (S.K.P.); the Department of Radiation Oncology, Princess Margaret Cancer Centre and University of Toronto (D.H.), and the Division of Hematology-Oncology, Hospital for Sick Children and University of Toronto (A.P.), Toronto, and the Department of Radiation Oncology, Centre Hospitalier de l'Université de Montréal, Montreal (A.-M.C.) - all in Canada; Imaging and Radiation Oncology Core Rhode Island, Lincoln (K.M.); the Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston (T.H.); the Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison (S.C.); the Department of Pediatrics, Children's National Hospital, and George Washington School of Medicine and Health Sciences, Washington, DC (H.D.); the Department of Pediatrics, University of Chicago Pritzker School of Medicine, Comer Children's Hospital, Chicago (T.O.H.); and the Department of Pediatrics, Roswell Park Comprehensive Cancer Center, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY (K.M.K.).
• N. Engl. J. Med. 2022 Nov 3; 387 (18): 164916601649-1660.

BackgroundIn adults with advanced-stage Hodgkin's lymphoma, the CD30-directed antibody-drug conjugate brentuximab vedotin combined with multiagent chemotherapy has been shown to have greater efficacy, but also more toxic effects, than chemotherapy alone. The efficacy of this targeted therapy approach in children and adolescents with Hodgkin's lymphoma is unclear.MethodsWe conducted an open-label, multicenter, randomized, phase 3 trial involving patients 2 to 21 years of age with previously untreated Hodgkin's lymphoma of stage IIB with bulk tumor or stage IIIB, IVA, or IVB. Patients were assigned to receive five 21-day cycles of brentuximab vedotin with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide (brentuximab vedotin group) or the standard pediatric regimen of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (standard-care group). Slow-responding lesions, defined by a score of 4 or 5 (on a 5-point scale, with scores of 1 to 3 indicating rapid-responding lesions), were identified on centrally reviewed positron-emission tomography-computed tomography after two cycles. Involved-site radiation therapy was administered after the fifth cycle of therapy to slow-responding lesions and to large mediastinal adenopathy that was present at diagnosis. The primary end point was event-free survival, defined as the time until disease progression occurred, relapse occurred, a second malignant neoplasm developed, or the patient died. Safety and overall survival were assessed.ResultsOf 600 patients who were enrolled across 153 institutions, 587 were eligible. At a median follow-up of 42.1 months (range, 0.1 to 80.9), the 3-year event-free survival was 92.1% (95% confidence interval [CI], 88.4 to 94.7) in the brentuximab vedotin group, as compared with 82.5% (95% CI, 77.4 to 86.5) in the standard-care group (hazard ratio for event or death, 0.41; 95% CI, 0.25 to 0.67; P<0.001). The percentage of patients who received involved-site radiation therapy did not differ substantially between the brentuximab vedotin group and the standard-care group (53.4% and 56.8%, respectively). Toxic effects were similar in the two groups. Overall survival at 3 years was 99.3% (95% CI, 97.3 to 99.8) in the brentuximab vedotin group and 98.5% (95% CI, 96.0 to 99.4) in the standard-care group.ConclusionsThe addition of brentuximab vedotin to standard chemotherapy resulted in superior efficacy, with a 59% lower risk of an event or death, and no increase in the incidence of toxic effects at 3 years. (Funded by the National Institutes of Health and others; AHOD1331 ClinicalTrials.gov number, NCT02166463.).Copyright © 2022 Massachusetts Medical Society.

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