Nivolumab-AVD Versus Brentuximab Vedotin–AVD in Older Patients With Advanced-Stage Classic Hodgkin Lymphoma Enrolled on S1826
Sarah C. Rutherford, Hongli Li, Alex F. Herrera, Michael LeBlanc, Sairah Ahmed, Kelly Davison, Susan K. Parsons, Joseph M. Unger, Anamarija M. Perry, Carla Casulo, Nancy L. Bartlett, Joseph M. Tuscano, Brian Hess, Pallawi Torka, Pankaj Kumar, Ryan Jacobs, Joo Y. Song, Sharon M. Castellino, Brad S. Kahl, John P. Leonard, Sonali M. Smith, Jonathan W. Friedberg, Andrew M. Evens
Abstract
Older patients with classic Hodgkin lymphoma (cHL) have inferior survival compared with younger patients. We report a subset analysis of older patients (60 years and older) enrolled in the phase three S1826 trial conducted by SWOG that randomly assigned patients with newly diagnosed advanced-stage (III-IV) cHL to six cycles of nivolumab (N)–AVD or brentuximab vedotin (BV)–AVD. Of 103 enrolled patients 60 years and older, 99 were eligible. At a median follow-up of 2.1 years, the 2-year progression-free survival was 89% after N-AVD (n = 50) and 64% after BV-AVD (n = 49, HR 0.24, 95%CI 0.09-0.63, 1-sided stratified log-rank P = .001). The 2-year OS was 96% with N-AVD versus 85% with BV-AVD (HR 0.16, 95%CI 0.03-0.75 stratified 1-sided log-rank P = .005). Six cycles were delivered without dose reduction in 69% on N-AVD and 26% on BV-AVD; 55% discontinued BV, and 14% discontinued nivolumab. The nonrelapse mortality was 16% with BV-AVD and 6% with N-AVD. Despite more neutropenia with N-AVD, febrile neutropenia, sepsis, and infections were higher with BV-AVD, as was peripheral neuropathy. Patient-reported outcomes of key adverse events confirmed the improved toxicity profile of N-AVD over BV-AVD. N-AVD was better tolerated and more effective than BV-AVD and is therefore a new standard of care for older patients with advanced-stage cHL fit for anthracycline-based combination therapy.