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Frontline brentuximab vedotin in combination with dacarbazine or bendamustine in patients aged ≥60 years with HL

Jonathan W. Friedberg, Andres Forero-Torres, Rodolfo E. Bordoni, Vivian J.M. Cline, Dipti Patel Donnelly, Patrick J. Flynn, Gregg Olsen, Robert Chen, Abraham Fong, Yinghui Wang and Christopher A. Yasenchak

Key points

  • BV+DTIC is an active and well-tolerated combination for patients aged ≥60 years with HL.

  • Though highly active at the doses evaluated, BV+bendamustine has unacceptable toxicity in patients aged ≥60 years with HL.

Abstract

Patients aged ≥60 years with treatment-naïve Hodgkin lymphoma (HL) have few treatment options and inferior survival due to treatment-related toxicities and comorbidities. This phase 2, non-randomized, open-label study evaluated tolerability, activity, and response duration with brentuximab vedotin (BV) monotherapy (results previously reported), BV+dacarbazine (DTIC), and BV+bendamustine. Patients had classical HL and were ineligible for or declined frontline chemotherapy. Twenty-two patients received 1.8 mg/kg BV+375 mg/m2 DTIC for up to 12 cycles, then 20 more received 1.8 mg/kg BV+90/70 mg/m2 bendamustine for up to 6 cycles (dose reduced due to toxicity). Subsequent BV monotherapy was allowed. Approximately 30 patients were to receive BV+bendamustine; however, serious adverse event incidence (65%) and 2 deaths on study led to discontinuation of bendamustine treatment and cessation of enrollment in this arm. Most patients had Stage III/IV disease and approximately half had ≥3 comorbidities or were impaired in ≥1 aspect that significantly interfered with quality of life. For BV+DTIC, objective response rate (ORR) was 100% and complete remission (CR) rate was 62%. To date, median progression-free survival (PFS) was 17.9 months (range, 4.2+, 29+) and median overall survival (OS) was not reached (range, 14.8+, 29+ months). For BV+bendamustine, ORR was 100% and CR rate was 88%. Neither the median PFS nor OS were reached (ranges, 2.9, 18+ months, and 2.9, 18.2+ months, respectively). For elderly patients with HL, BV+DTIC may be a frontline option based on tolerability and response duration. Despite activity, BV+bendamustine is not a tolerable regimen in these patients. The study is registered to www.clinicaltrials.gov as NCT01716806.

  • Submitted June 13, 2017.
  • Accepted October 3, 2017.