Updated results from a phase 3 clinical trial indicate that incorporating nivolumab into the first-line treatment of advanced-stage classic Hodgkin lymphoma (cHL) in adolescents and adults could significantly improve outcomes. The study, published in The New England Journal of Medicine, reveals that patients treated with nivolumab in combination with AVD (doxorubicin, vinblastine, and dacarbazine) experienced fewer side effects and a 50% lower risk of disease progression compared to those receiving the standard treatment of brentuximab vedotin plus AVD.
The SWOG S1826 trial, the largest classic Hodgkin lymphoma clinical trial within the National Clinical Trials Network (NCTN), enrolled 970 patients across 736 centers in the U.S. and Canada, including 237 adolescents aged 12-17. The inclusion of younger patients was facilitated by the advocacy of Kara Kelly, MD, of Roswell Park Comprehensive Cancer Center, and Sharon Castellino, MD, of Children’s Healthcare of Atlanta and Emory University School of Medicine.
Key Findings
The trial's primary endpoint was progression-free survival (PFS). After a median follow-up of 2.1 years, the two-year PFS rate was 92% in the nivolumab-AVD arm compared to 83% in the brentuximab vedotin-AVD arm (HR, 0.45; 95% CI, 0.30-0.65). This improvement was consistent across various patient subgroups, including age and disease stage.
Secondary endpoints also favored the nivolumab-AVD regimen. The two-year event-free survival (EFS) rate was 90% in the nivolumab arm versus 81% in the brentuximab vedotin arm (HR, 0.50; 95% CI, 0.36-0.71). Overall survival (OS) rates at two years were 99% and 98% in the nivolumab and brentuximab vedotin arms, respectively (HR, 0.39; 95% CI, 0.15-1.03).
Safety and Tolerability
Notably, the nivolumab-AVD regimen demonstrated a better safety profile. Fewer patients in the nivolumab arm discontinued treatment early (7.6% vs 12.0%) or experienced death during treatment (0.6% vs 1.7%). While neutropenia was more common in the nivolumab arm (56% vs 34%), most other adverse events were less frequent compared to the brentuximab vedotin arm.
Alex Herrera, MD, chief of the Division of Lymphoma at City of Hope, stated that nivolumab with AVD chemotherapy is a well-tolerated and highly effective new standard of care for patients with stage III or IV Hodgkin lymphoma.
Impact on Clinical Practice
The study findings suggest a potential paradigm shift in the treatment of advanced-stage cHL. The improved efficacy and safety profile of nivolumab-AVD may lead to a reduction in the use of radiation therapy, particularly in pediatric patients, thus minimizing long-term side effects such as secondary cancers and infertility.
Kara Kelly, MD, emphasized the importance of this trial for pediatric patients, stating, "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."
Study Details
The trial was sponsored by the SWOG Cancer Research Network and funded by the National Cancer Institute, National Institutes of Health, with additional support from Bristol-Myers Squibb (BMS) and Seagen. Patients received intravenous nivolumab at 240 mg (adults) or 3 mg/kg (adolescents) or brentuximab vedotin at 1.2 mg/kg, combined with doxorubicin at 25 mg/m2, vinblastine at 6 mg/m2, and dacarbazine at 375 mg/m2.
Jonathan W. Friedberg, MD, of Wilmot Cancer Institute and the University of Rochester, served as the corresponding author, and Alex F. Herrera, MD, of City of Hope Comprehensive Cancer Center, was the first author.
