Kara Kelly, MD
Roswell Park’s Chair of Pediatrics reports clinical trial results to American Society of Hematology
BUFFALO, N.Y. — Replacing brentuximab vedotin with nivolumab in first-line treatment combined with the chemotherapy regimen AVD improved progression-free survival in pediatric patients with newly diagnosed, advanced-stage classic Hodgkin lymphoma (cHL), report the authors of a phase 3 clinical trial sponsored by SWOG Cancer Research Network and were presented by senior author Kara Kelly, MD, Chair of Pediatric Oncology at Roswell Park Comprehensive Cancer Center, during the 2023 annual meeting of the American Society of Hematology in San Diego, California.
The largest Hodgkin lymphoma clinical trial in the history of the National Clinical Trials Network (NCTN), an umbrella network that includes SWOG, the study (ASH 2023 abstract 610) enrolled a total of 976 patients, both adult and pediatric, including 237 eligible patients between the ages of 12-17.
The 1:1 randomized clinical trial assigned participants to two groups. One received brentuximab vedotin (brand name Adcetris) — an antibody drug conjugate — along with AVD, a chemotherapy regimen combining doxorubicin, vinblastine and dacarbazine. The second group received nivolumab (brand name Opdivo) — an immune checkpoint inhibitor that binds to PD-1, a protein that prevents the immune system from destroying cHL — plus AVD. At the end of treatment, patients with residual metabolically active lesions received radiation therapy.
Progression-free survival at one year was higher in the nivolumab-AVD (N-AVD) group (94%) vs. the brentuximab vedotin-AVD (BV-AVD) group (88%). Both nivolumab and brentuximab vedotin were well tolerated, although, as expected, patients in the BV-AVD group experienced more overall sensory neuropathy, and thyroid disease was more prevalent among those in the N-AVD group.
Given the delayed toxic effects of radiation therapy, the study results revealed a significant benefit for pediatric patients in the fact that radiation therapy was required in less than 1% of participants in both arms — much lower than the 50-65% seen in historical trials for pediatric cHL.
The research team notes that longer follow-up is required to better understand the potential roles of the two treatment regimens for advanced-stage cHL.
“This successful collaboration between pediatric and adult lymphoma investigators led to the trial meeting its accrual goals a year earlier than anticipated, and facilitated earlier access to PD-1 inhibitors in frontline treatment for adolescents with advanced stage classic Hodgkin lymphoma,” says Dr. Kelly, who also leads the Roswell Park Oishei Children’s Cancer and Blood Disorders Program, serves as Chief of Pediatric Hematology/Oncology at the University at Buffalo Jacobs School of Medicine and Biomedical Sciences and was recently named Chair of the National Comprehensive Cancer Network (NCCN) Guidelines Panel on Pediatric Hodgkin Lymphoma.
Building on that collaboration, a similar strategy is being evaluated in children and adults with early-stage cHL through a recently activated phase 3 clinical trial led by the NCTN’s Children’s Oncology Group and co-chaired by Dr. Kelly. It will be discussed in an ASH poster presentation of which Dr. Kelly is senior author: “A Randomized Phase 3 Response-Adapted Trial Comparing Standard Therapy with Immuno-Oncology Therapy for Children and Adults with Newly Diagnosed Stage I and II Classic Hodgkin Lymphoma,”