City of Hope® doctor-led research published in the New England Journal of Medicine
Adolescent and adult patients with advanced classic Hodgkin lymphoma who received initial treatment with nivolumab plus AVD chemotherapy had roughly one-half the risk of progression or death of those patients treated with a standard combination of brentuximab vedotin plus AVD
Trial data expected to change standard of care therapy for Hodgkin lymphoma
Contact:
Letisia Marquez
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626-476-7593
LOS ANGELES – City of Hope®, one of the largest and most advanced cancer research and treatment organizations in the U.S. and ranked among the nation’s top 5 cancer centers by U.S. News & World Report, announced today that the SWOG S1826 Phase 3 clinical trial has demonstrated that patients with Stage 3 or 4 classic Hodgkin lymphoma who underwent initial treatment with nivolumab, a PD-1 checkpoint inhibitor, combined with chemotherapy, had significantly better outcomes than patients treated with standard chemotherapy plus brentuximab vedotin (BV), an antibody-drug conjugate, two years after starting treatment, according to a New England Journal of Medicine study published today.
In mid-2023, the trial reported highly positive primary results earlier than expected, after the trial’s second planned interim analysis found the preset threshold for efficacy had already been reached.
Now, a follow-up analysis with additional data — a median follow-up of 2.1 years — confirms the durability of those initial findings: among the 970 newly diagnosed adolescents and adults randomized to the trial, those who received a combination of nivolumab plus AVD chemotherapy (N-AVD) had a significantly lower risk of cancer progression or death than those treated with a standard combination of BV-AVD.
“Nivolumab with AVD chemotherapy is a well-tolerated and highly effective new standard of care for patients with Stage 3 or 4 Hodgkin lymphoma,” said Alex Herrera, M.D., the study’s first author, the trial’s lead investigator and City of Hope chief of the Division of Lymphoma. “It’s critical to be able to offer these patients a safe and effective therapy that can put their cancer into long-term remission.
“With these promising results, we expect nivolumab with AVD chemotherapy will become a new standard of care and the first treatment we provide patients who are diagnosed with advanced stage Hodgkin lymphoma,” Herrera added.
“This new analysis with more patient follow-up is critical to understanding the clinically meaningful benefit obtained from N-AVD compared to BV-AVD,” said Michael LeBlanc, Ph.D., lead biostatistician on the S1826 study. LeBlanc is group statistician of the SWOG Cancer Research Network, director of the SWOG Statistics and Data Management Center, and professor of biostatistics at the Fred Hutchinson Cancer Center.
Two-year progression-free survival was 92% on the N-AVD arm compared to 83% on the BV-AVD arm. This benefit was consistent across pre-specified patient subgroups, including by patient age, disease stage and International Prognostic Score.
Overall, the N-AVD treatment was also better tolerated than BV-AVD (AVD chemotherapy is a combination of doxorubicin/Adriamycin, vinblastine and dacarbazine). Fewer patients discontinued nivolumab treatment early in the N-AVD arm (9.4%) compared to brentuximab vedotin discontinuation in the BV arm (22.2%) and fewer deaths occurred during treatment (0.6 percent of patients versus 1.7%). The rates of most side effects were also lower on the N-AVD arm.
The differences in toxicity between the two treatments were particularly pronounced in patients older than 60 years of age. On the BV-AVD arm, this group of patients had a higher mortality rate than younger patients, and roughly one-third had to discontinue treatment early because of toxicity, whereas patients older than 60 on the N-AVD arm did not experience significantly higher morbidity or mortality rates than their younger counterparts. Notably, less than 1% of patients received radiation therapy.
The S1826 trial is supported by the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), and led by the SWOG Cancer Research Network, in collaboration with the Children’s Oncology Group and with participation from other NCI-funded National Clinical Trials Network (NCTN) groups. It is the largest classic Hodgkin lymphoma study ever conducted in the NCTN and reflects a successful collaboration between pediatric and adult lymphoma investigators, enabling earlier evaluation of promising novel therapies in adolescents with Hodgkin lymphoma in frontline treatment.
S1826 was funded by the NIH/NCI through grants U10CA180888, U10CA180819, U10CA180821, U10CA180820, U10CA180863 and UG1CA189955, with additional support provided by Bristol-Myers Squibb (BMS) through a Cooperative Research and Development Agreement between the NCI and BMS. Brentuximab vedotin was provided by Seagen.
In addition to LeBlanc, authors on the publication include corresponding author Jonathan W. Friedberg, M.D., M.M.Sc., Wilmot Cancer Institute, University of Rochester; Sharon M. Castellino, M.D., M.Sc., Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University Hospital/Winship Cancer Institute; Hongli Li, M.S., SWOG Statistics and Data Management Center; Sarah C. Rutherford, M.D., Weill Cornell Medicine; Andrew M. Evens, D.O., M.B.A., M.Sc., Rutgers Cancer Institute of New Jersey; Kelly Davison, M.D., Ph.D., McGill University Health Centre; Angela Punnett, M.D., SickKids Hospital; Susan K. Parsons, M.D., M.R.P., Reid R. Sacco AYA Cancer Program, Tufts Medical Center; Sairah Ahmed, M.D., MD Anderson Cancer Center; Carla Casulo, M.D., Wilmot Cancer Institute, University of Rochester; Nancy L. Bartlett, M.D., Siteman Cancer Center, Washington University; Joseph M. Tuscano, M.D., UC Davis Comprehensive Cancer Center; Matthew G. Mei, M.D., City of Hope; Brian T. Hess, M.D., Medical University of South Carolina; Ryan Jacobs, M.D., Carolinas Medical Center/Levine Cancer Institute; Hayder Saeed, M.D., Moffitt Cancer Center; Pallawi Torka, M.D., Memorial Sloan Kettering Cancer Center; Boyu Hu, M.D., Huntsman Cancer Institute, University of Utah; Craig Moskowitz, M.D., Sylvester Comprehensive Cancer Center, University of Miami; Supreet Kaur, M.D., University of Texas HSC at San Antonio; Gaurav Goyal, M.D., University of Alabama at Birmingham; Christopher Forlenza, M.D., Children’s Hospital Los Angeles; Andrew Doan, M.D., Children’s Hospital Los Angeles; Adam Lamble, M.D., Seattle Children’s Hospital; Pankaj Kumar, M.D., Illinois CancerCare; Saeeda Chowdury, M.D., Prisma Health Cancer Institute – Eastside; Brett Brinker, M.D., M.S., Cancer & Hematology Center - W Michigan; Namita Sharma, M.D., Geisinger Community Medical Center - Hematology and Oncology; Avina Singh, M.D., Fairview Ridges Hospital, Minnesota Oncology; Kristie A. Blum, M.D., Emory University Hospital/Winship Cancer Institute; Anamarija M. Perry, M.D., University of Michigan; Alexandra Kovach, M.D., Children’s Hospital Los Angeles; David Hodgson, M.D., M.P.H., Princess Margaret Cancer Centre; Louis S. Constine, M.D., Wilmot Cancer Institute, University of Rochester; Lale Kostakoglu Shields, M.D., NYU Langone; Anca Prica, M.D., Princess Margaret Cancer Centre; Hildy Dillon, M.P.H., SWOG Cancer Research Network; Richard F. Little, M.D., National Cancer Institute, Cancer Therapy Evaluation Program; Margaret A. Shipp, M.D., Dana-Farber Cancer Institute; Michael Crump, M.D., Princess Margaret Cancer Centre; Brad Kahl, M.D., Siteman Cancer Center, Washington University; John P. Leonard, M.D., Weill Cornell Medicine; Sonali M. Smith, M.D., University of Chicago; Joo Y. Song, M.D., City of Hope; Kara M. Kelly, M.D., Roswell Park Comprehensive Cancer Center; and Jonathan W. Friedberg, M.D., M.M.Sc., Wilmot Cancer Institute, University of Rochester.
About City of Hope
City of Hope's mission is to make hope a reality for all touched by cancer and diabetes. Founded in 1913, City of Hope has grown into one of the largest and most advanced cancer research and treatment organizations in the U.S., and one of the leading research centers for diabetes and other life-threatening illnesses. City of Hope research has been the basis for numerous breakthrough cancer medicines, as well as human synthetic insulin and monoclonal antibodies. With an independent, National Cancer Institute-designated comprehensive cancer center that is ranked top 5 in the nation for cancer care by U.S. News & World Report at its core, City of Hope’s uniquely integrated model spans cancer care, research and development, academics and training, and a broad philanthropy program that powers its work. City of Hope’s growing national system includes its Los Angeles campus, a network of clinical care locations across Southern California, a new cancer center in Orange County, California, and cancer treatment centers and outpatient facilities in the Atlanta, Chicago and Phoenix areas. City of Hope’s affiliated group of organizations includes Translational Genomics Research Institute and AccessHopeTM. For more information about City of Hope, follow us on Facebook, X, YouTube, Instagram and LinkedIn.