Brentuximab vedotin plus adriamycin and dacarbazine in nonbulky limited-stage Hodgkin lymphoma: results of a phase 2 trial

ABVD with or without radiation has been standard treatment for limited stage HL but carries risks of bleomycin-lung injury and radiation toxicity. Brentuximab vedotin (BV) is approved with AVD as frontline therapy for stage III-IV HL, but carries increased risks of peripheral neuropathy (PN) and neutropenic fever, likely due to overlapping toxicity between BV and vinblastine. We therefore evaluated BV in combination with AD for 4 or 6 cycles based on interim PET response. Thirty-four patients with non-bulky stage I-II HL were enrolled with a median age of 36. Risk was early favorable in 53%, unfavorable in 47%. The overall and complete response rates were 100% and 97%, respectively, with a 5-year PFS of 91%. No differences in outcome were observed based on stage (I vs II) or risk status (early favorable vs unfavorable). The most common adverse events were nausea (85%), peripheral sensory neuropathy (59%) and fatigue (56%). There were no cases of grade 4 neutropenia or neutropenic fever, and no patients received G-CSF. Most cases of peripheral neuropathy were grade 1 and no patients experienced grade ≥3 peripheral neuropathy. BV-AD produced a high CR rate and durable PFS with most patients requiring only 4 cycles of therapy. Compared to BV-AVD, the toxicity profile appeared improved with the omission of vinblastine, with predominantly grade 1 reversible peripheral neuropathy, and no cases of grade 4 neutropenia or neutropenic fever. This promising regimen warrants further study in Hodgkin lymphoma and may serve as a backbone for the addition of novel agents. This trial is registered on clinicaltrials.gov (NCT02505269).