Bortezomib, melphalan, and prednisone in elderly patients with relapsed/refractory multiple myeloma: a multicenter, open label phase 1/2 study

Cancer. 2013 Mar 1;119(5):971-7. doi: 10.1002/cncr.27820. Epub 2012 Oct 23.

Abstract

Background: In elderly patients with newly diagnosed multiple myeloma (MM), the addition of bortezomib to standard, combined oral melphalan and prednisone (MP) significantly increases the response rate and event-free survival compared with MP alone.

Methods: In this phase 1/2 trial, the authors assessed the dosing, efficacy, and safety of a lower dose-intensity MP schedule plus weekly bortezomib as salvage treatment for elderly patients with MM. To assess the maximum tolerated dose, 19 patients who had relapsed/refractory MM after 1 or 2 lines of treatment entered the first phase of the study. They received melphalan at a dose of 24 mg for 28 days; bortezomib 1.3 mg/m(2) on days 1, 8, 15, and 22; and prednisone at a dose of 50 mg every other day of a 28-day cycle for a total of 9 cycles. At the end of the first phase, based on the good efficacy and acceptable toxicity of this combination, an additional 23 patients were enrolled.

Results: After a median follow-up of 21 months, of 42 patients who relapsed, 24 (57%) obtained at least a partial response, 4 had stable disease, and 11 had progressive disease. The median time to progression was 18 months, and the median overall survival was 30 months. Grade 3 and 4 toxicity was observed in 16 of 42 patients (38%) and was more frequent during the early cycles.

Conclusions: A weekly infusion of bortezomib associated with lower dose-intensity MP induced a high proportion of responses and was well tolerated in elderly patients with relapsed/refractory MM.

Publication types

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

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Boronic Acids / administration & dosage
  • Bortezomib
  • Disease-Free Survival
  • Female
  • Humans
  • Male
  • Maximum Tolerated Dose
  • Melphalan / administration & dosage
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / mortality
  • Prednisone / administration & dosage
  • Pyrazines / administration & dosage
  • Recurrence

Substances

  • Boronic Acids
  • Pyrazines
  • Bortezomib
  • Melphalan
  • Prednisone