Breakthrough Clinical Trial Reveals Better Treatment for Advanced Classic Hodgkin Lymphoma

ATLANTA and Buffalo, N.Y. (Oct. 17, 2024)— Updated results from a phase 3 clinical trial led at the Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta by Sharon Castellino, MD, MSc, Director of the Leukemia and Lymphoma Program, in collaboration with Kara Kelly, MD, of Roswell Park Comprehensive Cancer Center and a nationwide team of lymphoma experts, are expected to change the way advanced stage classic Hodgkin lymphoma is treated in newly diagnosed adolescents and adults. Results were published yesterday in The New England Journal of Medicine.

Data from the trial show that patients who received nivolumab (brand name Opdivo) experienced fewer side effects and had a 50% lower risk that the disease would progress after treatment, compared with patients who received the standard treatment, brentuximab vedotin (BV— brand name Adcetris). Patients in both groups also received AVD, a chemotherapy cocktail.

Nivolumab is a type of immunotherapy called an immune checkpoint inhibitor, which works by releasing the immune system's brakes so it can destroy classic Hodgkin lymphoma cells. Brentuximab vedotin is an antibody drug conjugate, which combines an antibody and a chemotherapy drug that work together to zero in on cancer cells and selectively destroy them.

The largest classic Hodgkin lymphoma clinical trial ever conducted in the National Clinical Trials Network (NCTN), the study enrolled 970 patients — including 237 between ages 12-17 — at 736 centers in the U.S. and Canada. Younger patients were able to participate in the clinical trial thanks to the leadership and advocacy of Dr. Castellino, pediatric study chair for the trial, and Dr. Kelly, the Waldemar J. Kaminski Endowed Chair of Pediatrics at Roswell Park Comprehensive Cancer Center.

The clinical trial is especially important because classic Hodgkin lymphoma is one of the most common cancers in people ages 12-39.

“We anticipate that by working with the adult groups in this practice-changing clinical trial, we have paved the way for pediatric patients with advanced stage Hodgkin lymphoma to gain earlier access to checkpoint inhibitors”, says Dr. Kelly. “If we had had to wait to perform a trial for pediatric patients after the adult trial was complete, it could have taken six years or more.” Dr. Kelly is also Chair of the Roswell Park Oishei Children's Cancer and Blood Disorders Program, Division Chief of Department of Pediatrics for the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo and Division Chief of Pediatric Hematology/Oncology at UBMD Pediatrics.

“The high rate of progression-free survival with Nivolumab–AVD represents another paradigm shift incorporating immunotherapy into the frontline treatment of advanced stage classic Hodgkin Lymphoma for adolescents 12 and older with a dramatic reduction and near elimination of the need for radiation therapy,” said Dr. Castellino, who is also a professor of pediatrics at Emory University School of Medicine, and a research member of Winship Cancer Institute of Emory University. “This has significant implications toward reducing the risk of radiation associated late effects in the growing child and adolescent.”

The study launched in 2019, and Dr. Kelly presented positive preliminary results last year at the annual meeting of the American Society of Hematology. Investigators have continued to track the progress of the participants since then, with most of the recent follow-ups occurring at 2.1 years.

Jonathan W. Friedberg, MD, MMSc, of Wilmot Cancer Institute and the University of Rochester, is corresponding author on the new publication and Alex F. Herrera, MD, of City of Hope Comprehensive Cancer Center is first author.

Sponsored by the SWOG Cancer Research Network, the study was funded by the National Cancer Institute, National Institutes of Health, through grants U10CA180888, U10CA180819, U10CA180821, U10CA180820, U10CA180863 and UG1CA189955, with additional support from Bristol-Myers Squibb (BMS) and Seagen.