• Alex F Herrera, Michael LeBlanc, Sharon M Castellino, Hongli Li, Sarah C Rutherford, Andrew M Evens, Kelly Davison, Angela Punnett, Susan K Parsons, Sairah Ahmed, Carla Casulo, Nancy L Bartlett, Joseph M Tuscano, Matthew G Mei, Brian T Hess, Ryan Jacobs, Hayder Saeed, Pallawi Torka, Boyu Hu, Craig Moskowitz, Supreet Kaur, Gaurav Goyal, Christopher Forlenza, Andrew Doan, Adam Lamble, Pankaj Kumar, Saeeda Chowdhury, Brett Brinker, Namita Sharma, Avina Singh, Kristie A Blum, Anamarija M Perry, Alexandra Kovach, David Hodgson, Louis S Constine, Lale Kostakoglu Shields, Anca Prica, Hildy Dillon, Richard F Little, Margaret A Shipp, Michael Crump, Brad Kahl, John P Leonard, Sonali M Smith, Joo Y Song, Kara M Kelly, and Jonathan W Friedberg.
• From City of Hope Comprehensive Cancer Center, Duarte (A.F.H., M.G.M., J.Y.S.), University of California Davis Comprehensive Cancer Center, Sacramento (J.M.T.), and Children's Hospital Los Angeles, Los Angeles (C.F., A.D., A.K.) - all in California; SWOG Statistics and Data Management Center, Fred Hutchinson Cancer Center, (M.L., H.L.) and Seattle Children's Hospital (A.L.) - both in Seattle; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta (S.M.C.), and Winship Cancer Institute and Emory University Hospital (K.A.B.), Atlanta; Weill Cornell Medicine (S.C.R., J.P.L.), Memorial Sloan Kettering Cancer Center (P.T.), and New York University Langone (L.K.S.), New York, Wilmot Cancer Institute, University of Rochester, Rochester (C.C., L.S.C., J.W.F.), and Roswell Park Comprehensive Cancer Center, University at Buffalo, Buffalo (K.M.K.) - all in New York; Rutgers Cancer Institute of New Jersey, New Brunswick (A.M.E.); McGill University Health Centre, Montreal (K.D.), and SickKids Hospital (Angela Punnett) and Princess Margaret Cancer Centre (D.H., Anca Prica, M.C.), Toronto - all in Canada; Reid R. Sacco AYA Cancer Program, Tufts Medical Center (S.K.P.), and Dana-Farber Cancer Institute (M.A.S.) - both in Boston; M.D. Anderson Cancer Center, Houston (S.A.), and University of Texas Health Science Center at San Antonio, San Antonio (S.K.) - both in Texas; Siteman Cancer Center, Washington University, St. Louis (N.L.B., B.K.); Medical University of South Carolina, Charleston (B.T.H.), and Prisma Health Cancer Institute - Eastside, Greenville (S.C.) - both in South Carolina; Carolinas Medical Center, Levine Cancer Institute, Charlotte, NC (R.J.); Moffitt Cancer Center, Tampa (H.S.), and Sylvester Comprehensive Cancer Center, University of Miami, Miami (C.M.) - both in Florida; Huntsman Cancer Institute, University of Utah, Salt Lake City (B.H.); University of Alabama at Birmingham, Birmingham (G.G.); Illinois CancerCare, Peoria (P.K.), and University of Chicago, Chicago (S.M.S.); Cancer and Hematology Centers of Western Michigan, Grand Rapids (B.B.), and University of Michigan, Ann Arbor (A.M.P.); the Department of Hematology and Oncology, Geisinger Community Medical Center, Scranton, PA (N.S.); Fairview Ridges Hospital, Minnesota Oncology, Burnsville (A.S.); SWOG Cancer Research Network, Teaneck, NJ (H.D.); and the National Cancer Institute, Cancer Therapy Evaluation Program, Bethesda, MD (R.F.L.).
• N. Engl. J. Med. 2024 Oct 17; 391 (15): 137913891379-1389.

BackgroundIncorporating brentuximab vedotin into the treatment of advanced-stage classic Hodgkin's lymphoma improves outcomes in adult and pediatric patients. However, brentuximab vedotin increases the toxic effects of treatment in adults, more than half of pediatric patients who receive the drug undergo consolidative radiation, and relapse remains a challenge. Programmed death 1 blockade is effective in Hodgkin's lymphoma, including in preliminary studies involving previously untreated patients.MethodsWe conducted a phase 3, multicenter, open-label, randomized trial involving patients at least 12 years of age with stage III or IV newly diagnosed Hodgkin's lymphoma. Patients were randomly assigned to receive brentuximab vedotin with doxorubicin, vinblastine, and dacarbazine (BV+AVD) or nivolumab with doxorubicin, vinblastine, and dacarbazine (N+AVD). Prespecified patients could receive radiation therapy directed to residual metabolically active lesions. The primary end point was progression-free survival, defined as the time from randomization to the first observation of progressive disease or death from any cause.ResultsOf 994 patients who underwent randomization, 970 were included in the intention-to-treat population for efficacy analyses. At the second planned interim analysis, with a median follow-up of 12.1 months, the threshold for efficacy was crossed, indicating that N+AVD significantly improved progression-free survival as compared with BV+AVD (hazard ratio for disease progression or death, 0.48; 99% confidence interval [CI], 0.27 to 0.87; two-sided P = 0.001). Owing to the short follow-up time, we repeated the analysis with longer follow-up; with a median follow-up of 2.1 years (range, 0 to 4.2 years), the 2-year progression-free survival was 92% (95% CI, 89 to 94) with N+AVD, as compared with 83% (95% CI, 79 to 86) with BV+AVD (hazard ratio for disease progression or death, 0.45; 95% CI, 0.30 to 0.65). Overall, 7 patients received radiation therapy. Immune-related adverse events were infrequent with nivolumab; brentuximab vedotin was associated with more treatment discontinuation.ConclusionsN+AVD resulted in longer progression-free survival than BV+AVD in adolescents and adults with stage III or IV advanced-stage classic Hodgkin's lymphoma and had a better side-effect profile. (Funded by the National Cancer Institute of the National Institutes of Health and others; S1826 ClinicalTrials.gov number, NCT03907488.).Copyright © 2024 Massachusetts Medical Society.

38 keywords...

hide…