Nivolumab+AVD in Advanced-Stage Classic Hodgkin’s Lymphoma
This is not only safer (less toxicity with nivo) but reduced disease progression or death by 52%.
AbstractOlder 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. 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.
This is not only safer (less toxicity with nivo) but reduced disease progression or death by 52%.
Pembro + ICE seems to be a compelling option in the 2L setting for transplant eligible cHL patients, however this is not yet in guidelines.
Pembro + AVD for 1L treatment of cHL was associated with excellent responses, PFS and clearance of ctDNA. IO+chemo seems to be a growing trend in HL in various settings and theses response rates in non-Bleo regimens are very encouraging. The ongoing trial NCT05675410 comparing BV+AVD vs. Nivo+AVD should be a pivotal trial when complete.