Roswell Park and Children’s Healthcare of Atlanta Analysis Confirms Benefit of Nivolumab Combo in Teens With Advanced Hodgkin Lymphoma

ATLANTA, Ga., and BUFFALO, N.Y. — Teens with advanced-stage Hodgkin lymphoma survive longer without their disease getting worse when they receive the immunotherapy nivolumab (Opdivo) instead of the immunotherapy brentuximab vedotin (brand name Adcetris) along with chemotherapy, according to the updated results of a subset analysis of a landmark phase 3 clinical trial. Kara Kelly, MD, of Roswell Park Comprehensive Cancer Center, is senior author of the analysis, published Jan. 9 in the Journal of Clinical Oncology, and Sharon Castellino, MD, MSc, of the Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta and Emory University School of Medicine, is first author.

The authors conclude the evidence supports lowering to 12 the minimum age for receiving nivolumab, a checkpoint inhibitor, which “releases the brakes” on the immune system. As a result, the National Comprehensive Cancer Center (NCCN) guidelines, used worldwide as the gold standard for treatment recommendations, have been updated to reflect this newly discovered best practice of combining nivolumab with a chemotherapy combination called AVD for adolescents newly diagnosed with stage 3-4 classic Hodgkin lymphoma (cHL).  

“This was the first Hodgkin lymphoma clinical trial to enroll adolescents along with adults,” says Dr. Kelly, who is the Waldemar J. Kaminski Endowed Chair of Pediatrics at Roswell Park, Chair of the Roswell Park Oishei Children’s Cancer and Blood Disorders Program and Division Chief for Pediatrics in the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo. “They represented the largest cohort in which the use of a checkpoint inhibitor was evaluated as a first-line treatment in a pediatric population.”

The research team’s subset analysis focused on outcomes for a cohort of 240 adolescents, ages 12-17, who were part of a larger study that enrolled 994 patients, including adults. Half the patients were randomly assigned to receive the antibody drug conjugate brentuximab vedotin plus AVD, a chemotherapy regimen combining doxorubicin, vinblastine and dacarbazine. The other half received AVD plus nivolumab, which binds to PD-1, a protein that prevents the immune system from destroying cHL.

Results from the one-year follow-up, reported in 2023, documented progression-free survival of 94% in the nivolumab-AVD group of adolescents compared with 88% in the brentuximab vedotin-AVD group. The current study indicates stability of the benefit of nivolumab in the three-year follow-up, with a 93% progression-free survival rate in the nivolumab-AVD group vs. 82% in the brentuximab vedotin-AVD group. 

Dr. Kelly adds that the treatment regimen evaluated in the study revealed an important benefit: It was associated with a significant reduction in the need for radiation therapy, also called radiotherapy. “Historically, 50-70% of pediatric patients with advanced-stage Hodgkin lymphoma require radiation, but this regimen slashed that to less than 1%,” she says, noting that only one patient in the nivolumab-AVD group and two in the brentuximab vedotin-AVD group required radiotherapy. “We believe this will limit long-term side effects such as breast cancer and heart disease in these young patients.”

Patients in the nivolumab-AVD arm also experienced fewer of most adverse side effects compared to those who received brentuximab -AVD.

”The study indicates the ability for pediatric and adult oncologists to collaborate to safely accelerate the time to access  novel therapies for teens with lymphoma by including them in trials with adult patients,” says Dr. Castellino, who is Director of Leukemia and Lymphoma at the Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta, the Mark R. Hudgens Chair of Clinical Research and Professor of Pediatrics at Emory University School of Medicine as well as a research member at Winship Cancer Institute of Emory University. 

Sponsored by the SWOG (formerly Southwest Oncology Group) Cancer Research Network, the clinical trial was the largest trial for people with Hodgkin lymphoma to be conducted collaboratively by institutions in the National Clinical Trials Network, an umbrella network that includes SWOG.

The research team also included collaborators from the SWOG Statistics and Data Management Center at Fred Hutchinson Cancer Center, City of Hope with lead study chair Alex Herrera, MD, Tufts Medical Center, Boston, The Hospital for Sick Children, Princess Margaret Hospital and the University of Toronto, Rutgers Cancer Institute New Jersey, Seattle Children’s, Memorial Sloan-Kettering Cancer Center, Children’s Hospital Los Angeles, Weill Cornell Medicine, the National Cancer Institute, Mayo Clinic-Jacksonville, the University of Chicago and Wilmot Cancer Center and the University of Rochester with SWOG chair Jonathan Friedberg, MD.

Additional support was provided by grants from the National Cancer Institute of the National Institutes of Health (project numbers U10CA180888, U10CA180819, U10CA180821, U10CA180820, U10CA180863, UG1CA189955 and R50CA285492), and by Bristol Myers Squibb, the Leukemia and Lymphoma Society, the Lymphoma Research Foundation, and the V Foundation. Bristol Myers Squibb and SeaGen provided drugs used in the trial.

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About Roswell Park Comprehensive Cancer Center
From the world’s first chemotherapy research to the PSA prostate cancer biomarker, Roswell Park Comprehensive Cancer Center generates innovations that shape how cancer is detected, treated and prevented worldwide. The Roswell Park team of 4,000+ makes compassionate, patient-centered cancer care and services accessible across New York State and beyond. Rated “Exceptional” by the National Cancer Institute, Roswell Park, founded in 1898, was one of the first NCI-designated comprehensive cancer centers in the country and remains the only one in Upstate New York. To learn more about Roswell Park Comprehensive Cancer Center and the Roswell Park Care Network, visit www.roswellpark.org, call 1-800-ROSWELL (1-800-767-9355) or email ASKRoswell@RoswellPark.org.

About Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta

The Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta is a national leader among childhood cancer, hematology, and blood and marrow transplant programs, serving children and young adults. Recognized as one of the top childhood cancer centers in the country by U.S. News & World Report, the Aflac Cancer and Blood Disorders Center cares for more than 9,500 patients yearly, of which nearly 500 are newly diagnosed cancer patients and treats more than 2,000 unique sickle cell disease patients each year. Our program offers patients access to more than 330 clinical trials, including 34 innovative Aflac Cancer and Blood Disorders Center investigator-initiated trials. Visit www.choa.org/cancer for more information.

About Children's Healthcare of Atlanta

As the only freestanding pediatric healthcare system in Georgia, Children’s Healthcare of Atlanta is the trusted leader in caring for kids. The not-for-profit organization’s mission is to make kids better today and healthier tomorrow through more than 60 pediatric specialties and programs, top healthcare professionals, and leading research and technology. Children’s is one of the largest pediatric clinical care providers in the country, managing more than one million patient visits annually at three hospitals (Arthur M. Blank, Hughes Spalding and Scottish Rite), Marcus Autism Center, the Center for Advanced Pediatrics, the Zalik Behavioral and Mental Health Center, urgent care centers and neighborhood locations. Consistently ranked among the top children’s hospitals by U.S. News & World Report, Children’s Healthcare of Atlanta has impacted the lives of kids in Georgia, across the United States and around the world for more than 100 years thanks to generous support from the community.