Nivolumab-AVD Improves Progression-Free Survival, Reduces Toxicity in Advanced Hodgkin Lymphoma

A recent phase 3 trial demonstrated that combining nivolumab with doxorubicin, vinblastine, and dacarbazine (N-AVD) chemotherapy improves 2-year progression-free survival (PFS) to 92%—compared to 83% with a brentuximab vedotin AVD (BV-AVD)—while also offering a superior safety profile in patients with advanced stage classic Hodgkin lymphoma (cHL).

This international, open-label study enrolled 994 patients aged 12 and older with newly diagnosed stage III or IV cHL at 256 centers across the United States and Canada. Of these, 970 patients were deemed eligible and were randomized in a 1:1 ratio to receive six cycles of either N-AVD or BV-AVD.

The primary endpoint was PFS. At an initial interim analysis with a median follow-up of 12.1 months, the study met its efficacy threshold with N-AVD demonstrating a 52% reduction in the risk of progression or death compared with BV-AVD (hazard ratio [HR]  = 0.48, P < .001). With extended follow-up to a median of 2.1 years, the 2-year PFS was 92% for N-AVD versus 83% for BV-AVD (HR = 0.45). These results were consistent across pre-specified subgroups including adolescents, adults, and older patients with cHL.

Patients receiving N-AVD had fewer treatment discontinuations and lower rates of severe adverse events, particularly a marked reduction in peripheral sensory neuropathy compared to the BV-AVD arm. Although neutropenia was more common with N-AVD, rates of febrile neutropenia, sepsis, and infections were similar between groups, aided by more frequent use of growth factor support in the BV-AVD arm.

“Based on the clinically meaningful improvement in progression-free survival and excellent tolerability of N-AVD, the ability to avoid potentially toxic consolidative radiation therapy, and decreased drug acquisition and supportive care costs, N-AVD should be a strong candidate for primary treatment for adolescent and adult patients with stage III-IV cHL,” the study authors concluded.

Reference
Herrera AF, LeBlanc M, Castellino SM, et al. Nivolumab+AVD in Advanced-Stage Classic Hodgkin's Lymphoma. N Engl J Med. 2024;391(15):1379-1389. doi:10.1056/NEJMoa240588