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Brentuximab Vedotin, Doxorubicin, Vinblastine and Dacarbazine for Non-bulky Limited Stage Classical Hodgkin Lymphoma

Jeremy S. Abramson, Jon E. Arnason, Ann S. LaCasce, Robert Redd, Jeffrey A. Barnes, Lubomir Sokol, Robin Joyce, David Avigan, Donna Neuberg, Ronald W. Takvorian, Ephraim P. Hochberg and Celeste M. Bello

Key Points

  • Brentuximab vedotin plus AVD without consolidative radiation is an effective therapy for non-bulky limited stage HL

  • Risk of peripheral neuropathy and neutropenic fever appear increased with brentuximab-AVD compared to expected toxicities of standard ABVD

Abstract

ABVD with or without radiation is standard therapy for limited stage HL but carries risks of bleomycin-lung injury and radiation toxicity. Brentuximab vedotin is highly active in relapsed HL and was recently approved with AVD in previously-untreated stage III-IV HL. We evaluated brentuximab-AVD for non-bulky stage I-II HL in a multicenter phase 2 study. Patients received a lead in cycle of brentuximab vedotin monotherapy on days 1 and 15, followed by an exploratory PET/CT scan. Patients then received brentuximab-AVD for 4-6 cycles based on interim PET/CT after cycle 2. Thirty-four patients were enrolled with a median age of 36 years (20-75). Risk was early favorable in 62%, unfavorable in 38%. The best CRR was 100%. At a median follow-up of 38 months, the PFS and OS were 94% and 97%. The most common adverse events were peripheral sensory neuropathy (79%), neutropenia (76%), fatigue (74%) and nausea (71%). The most common grade 3-4 toxicities were neutropenia (62%), febrile neutropenia (35%) and peripheral sensory neuropathy (24%). One elderly patient died of neutropenic sepsis in the first brentuximab-AVD cycle. Brentuximab dose reductions were required in 38% of patients, most for peripheral neuropathy. In conclusion, brentuximab-AVD without bleomycin or radiation produced a high CRR with most patients requiring only 4 total cycles of therapy. Toxicity was higher than would be expected from AVD alone, so may not be appropriate for early stage patients with a highly favorable prognosis. This trial is registered on clinical trials.gov (NCT01534078).

  • Submitted April 24, 2019.
  • Revision received June 11, 2019.
  • Accepted June 1, 2019.