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 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 enrol 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 paediatric 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 enroled 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 paediatric 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 paediatric 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.

Source: Roswell Park Comprehensive Cancer Center