A combination of nivolumab with AVD chemotherapy (doxorubicin, vinblastine, and dacarbazine) demonstrated a significant reduction in the risk of disease progression or death compared with brentuximab vedotin plus AVD in adolescent patients with newly diagnosed advanced classical Hodgkin lymphoma, according to 3-year findings from the adolescent cohort of the phase III S1826 trial that was published in the Journal of Clinical Oncology.
“This was the first Hodgkin lymphoma clinical trial to enroll adolescents along with adults,” said senior author Kara M. Kelly, MD, 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 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,” stated lead author Sharon M. Castellino, MD, MSc, 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, and a research member at Winship Cancer Institute of Emory University.
Study Methods
The randomized phase III trial enrolled a total of 994 patients with newly diagnosed advanced-stage (stages III and IV) classical Hodgkin lymphoma. Twenty-four percent of the overall population were adolescents between the ages of 12 and 17 years. All patients were randomly assigned to receive either nivolumab plus AVD or brentuximab vedotin plus AVD.
Key Findings
At 3 years, the progression-free survival rate in the cohort was 93% (95% confidence interval [CI] = 87%–96%) with nivolumab plus AVD as compared with 83% (95% CI = 73%–88%) with brentuximab vedotin and AVD (hazard ratio [HR] = 0.37; 95% CI = 0.17–0.80).
One patient in the nivolumab arm and two in the brentuximab vedotin arm received protocol-specified residual site radiotherapy.
“Historically, 50% to 70% of pediatric patients with advanced-stage Hodgkin lymphoma require radiation, but this regimen slashed that to less than 1%,” Dr. Kelly said, noting that only one patient in the nivolumab plus AVD group and two in the brentuximab vedotin plus AVD group required radiotherapy. “We believe this will limit long-term side effects such as breast cancer and heart disease in these young patients.”
The rates of both febrile neutropenia and sepsis were low in both arms. Severe immune-related adverse events were infrequent, but thyroid dysfunction was reported in 7% of patients in the nivolumab plus AVD arm. Sensory neuropathy of grade 2 or higher was observed more frequently in patients with brentuximab vedotin and AVD (14% vs 7%). Patient-reported outcomes also indicated that there was less toxicity with nivolumab over brentuximab vedotin.
No progression-free survival events were noted in the nivolumab arm, but there were 12 incidences of premature discontinuation of therapy in the nivolumab arm and 4 incidences in the brentuximab vedotin arm.
As a result of findings from the study, the NCCN Clinical Practice Guidelines in Oncology® for Hodgkin lymphoma have been updated to include the combination of nivolumab and AVD for the treatment of adolescent patients with newly diagnosed stage III to IV classical Hodgkin lymphoma. Additionally, the U.S. Food and Drug Administration recently granted a Priority Review Designation to nivolumab in combination with AVD for the treatment of adult and pediatric patients 12 years and older with previously untreated stage III or IV classical Hodgkin lymphoma.
DISCLOSURE: The study was sponsored by the SWOG (formerly Southwest Oncology Group) Cancer Research Network. Additional support was provided by grants from the National Cancer Institute of the National Institutes of Health and by Bristol Myers Squibb, the Leukemia and Lymphoma Society, the Lymphoma Research Foundation, and the V Foundation. For full disclosures of the study authors, visit ascopubs.org.
