Nivolumab+AVD or Brentuximab Vedotin+AVD in Advanced-Stage Hodgkin Lymphoma?

Survival in advanced-stage Hodgkin lymphoma is improved with brentuximab vedotin (BV) plus AVD (doxorubicin, vinblastine, dacarbazine) compared with the prior standard ABVD regimen (doxorubicin, bleomycin, vinblastine, dacarbazine; N Engl J Med 2022; 387:310). Given the high response rates to the PD-1 inhibitor nivolumab in patients with relapsed Hodgkin lymphoma and toxicities with BV, investigators compared the efficacy and safety of nivolumab combined with AVD (N+AVD) against BV+AVD in a multicenter, open-label, phase 3, randomized trial in patients aged 12 and older with newly diagnosed stage III or IV classic Hodgkin lymphoma. Radiation therapy was allowed for residual metabolically active sites of disease. Of the 970 evaluable patients, 24% were ages 12 to 17, and 10% were older than 60; 12% were Black, and 12% to 14% Hispanic.

Among the key findings:

• Progression-free survival (PFS), the primary outcome, was significantly improved with N+AVD compared with BV+AVD (hazard ratio for disease progression or death, 0.48).
• The 2-year PFS was 92% with N+AVD versus 83% with BV+AVD (HR, 0.45); only 7% of patients received radiation therapy.
• The rate of treatment discontinuation due to adverse events was lower with N+AVD than with BV+AVD (7.6% vs. 12.0%).
• Fewer patients treated with N+AVD experienced high-grade adverse events, such as peripheral neuropathy and neutropenia, compared with those receiving BV+AVD.