Gemcitabine and bendamustine is a safe and effective salvage regimen for patients with recurrent/refractory Hodgkin lymphoma: Results of a phase 1/2 study

Cancer. 2020 Mar 15;126(6):1235-1242. doi: 10.1002/cncr.32640. Epub 2019 Dec 10.

Abstract

Background: Both gemcitabine and bendamustine have been evaluated in patients with recurrent/refractory Hodgkin lymphoma but to the authors' knowledge not as a doublet. The authors completed a phase 1/2 trial to identify the optimal dose and frequency of administration and to assess the efficacy of this combination in patients with recurrent/refractory Hodgkin lymphoma.

Methods: Patients were treated up to a maximum dose of gemcitabine (1000 mg/m2 on day 1) and bendamustine (120 mg/m2 on days 1 and 2), which was determined to be the recommended phase 2 dose, administered every 21 days for up to 6 cycles. Patients could discontinue study therapy after 2 cycles to proceed with autologous or allogeneic stem cell transplantation.

Results: No dose-limiting toxicities were identified, but 4 patients experienced grade 3 to 5 pulmonary adverse events (toxicity was graded according to Common Terminology Criteria for Adverse Events [version 4]). A total of 26 patients were enrolled having completed a median of 4 prior lines of therapy (range, 1-7 lines), including 13 patients at the recommended phase 2 dose, in whom the overall response rate was 69% and the complete response rate was 46%. The median progression-free survival for the phase 2 patients was 11 months (95% CI, 3 months to not reached), and the median overall survival for this group had not been reached at the time of last follow-up (95% CI, 4 months to not reached).

Conclusions: This doublet was found to be tolerable and effective, but patients must be monitored closely for pulmonary toxicity. The authors currently are evaluating this doublet in combination with nivolumab.

Keywords: Hodgkin lymphoma; bendamustine; chemotherapy; clinical trial; gemcitabine.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bendamustine Hydrochloride / administration & dosage*
  • Bendamustine Hydrochloride / adverse effects
  • Bleomycin / administration & dosage
  • Bleomycin / adverse effects
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Drug Administration Schedule
  • Drug Resistance, Neoplasm
  • Female
  • Gemcitabine
  • Hodgkin Disease / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Progression-Free Survival
  • Recurrence
  • Salvage Therapy / methods*
  • Young Adult

Substances

  • Antibiotics, Antineoplastic
  • Deoxycytidine
  • Bleomycin
  • Bendamustine Hydrochloride
  • Gemcitabine