A recent phase 3 randomized controlled trial has demonstrated that the combination of nivolumab, doxorubicin, bleomycin, and dacarbazine (N+AVD) provides superior progression-free survival compared to brentuximab vedotin, doxorubicin, bleomycin, and dacarbazine (BV+AVD) in patients with newly diagnosed stage III or IV Hodgkin lymphoma. This finding suggests a potential shift in the standard first-line treatment for this patient population.
The study, which involved 994 adolescent and adult patients, compared the efficacy and safety of N+AVD versus BV+AVD. The primary endpoint was progression-free survival, and secondary endpoints included overall survival, event-free survival, and the incidence of adverse events. Patients were eligible if they were over 12 years old, had untreated stage III or IV Hodgkin lymphoma, and had a Zubrod performance score of 0 to 2 or a Lansky performance score of 50 to 100.
Key Findings on Efficacy
The results indicated a significant improvement in progression-free survival with N+AVD. At the second planned interim analysis, N+AVD was deemed to have significantly improved progression-free survival in comparison to the BV+AVD treatment (hazard ratio for disease progression or death, 0.48; 99% confidence interval [CI], 0.27 to 0.87; two-sided p=0.001). At the two-year mark, the progression-free survival for N+AVD-treated patients was 92% (95% CI, 89–94), compared to 83% for BV+AVD-treated patients (95% CI, 79–86) (hazard ratio for disease progression or death, 0.45; 95% CI, 0.30-0.65).
Event-free survival at two years was also higher in the N+AVD group (90%) compared to the BV+AVD group (81%) (stratified hazard ratio for death, 0.50; 95% CI, 0.36–0.71). Overall survival at two years was similar between the two groups, with 99% in the N+AVD group and 98% in the BV+AVD group (hazard ratio for death, 0.39; 95% CI, 0.15–1.03).
Safety Profile
Regarding safety, patients treated with BV+AVD experienced more frequent high-grade adverse events overall, except for neutropenia. Specifically, 22% more patients in the N+AVD group experienced grade 3 or higher neutropenia. However, no significant differences were found between the groups in terms of febrile neutropenia, sepsis, or infections.
Implications for Treatment
These findings suggest that N+AVD may offer a more favorable balance of efficacy and safety compared to BV+AVD for patients with advanced-stage Hodgkin lymphoma. The improved progression-free survival and manageable safety profile position N+AVD as a potential new standard of care in this setting.
Ongoing Research
Further studies are warranted to evaluate the long-term outcomes and potential benefits of N+AVD in diverse patient populations and to explore strategies for mitigating the risk of neutropenia associated with this regimen.
