Bortezomib or High-Dose Dexamethasone for Relapsed Multiple Myeloma

N Engl J Med. 2005 Jun 16;352(24):2487-98. doi: 10.1056/NEJMoa043445.

Abstract

Background: This study compared bortezomib with high-dose dexamethasone in patients with relapsed multiple myeloma who had received one to three previous therapies.

Methods: We randomly assigned 669 patients with relapsed myeloma to receive either an intravenous bolus of bortezomib (1.3 mg per square meter of body-surface area) on days 1, 4, 8, and 11 for eight three-week cycles, followed by treatment on days 1, 8, 15, and 22 for three five-week cycles, or high-dose dexamethasone (40 mg orally) on days 1 through 4, 9 through 12, and 17 through 20 for four five-week cycles, followed by treatment on days 1 through 4 for five four-week cycles. Patients who were assigned to receive dexamethasone were permitted to cross over to receive bortezomib in a companion study after disease progression.

Results: Patients treated with bortezomib had higher response rates, a longer time to progression (the primary end point), and a longer survival than patients treated with dexamethasone. The combined complete and partial response rates were 38 percent for bortezomib and 18 percent for dexamethasone (P<0.001), and the complete response rates were 6 percent and less than 1 percent, respectively (P<0.001). Median times to progression in the bortezomib and dexamethasone groups were 6.22 months (189 days) and 3.49 months (106 days), respectively (hazard ratio, 0.55; P<0.001). The one-year survival rate was 80 percent among patients taking bortezomib and 66 percent among patients taking dexamethasone (P=0.003), and the hazard ratio for overall survival with bortezomib was 0.57 (P=0.001). Grade 3 or 4 adverse events were reported in 75 percent of patients treated with bortezomib and in 60 percent of those treated with dexamethasone.

Conclusions: Bortezomib is superior to high-dose dexamethasone for the treatment of patients with multiple myeloma who have had a relapse after one to three previous therapies.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Boronic Acids / adverse effects
  • Boronic Acids / therapeutic use*
  • Bortezomib
  • Dexamethasone / administration & dosage
  • Dexamethasone / adverse effects
  • Dexamethasone / therapeutic use*
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Hematologic Diseases / chemically induced
  • Humans
  • Male
  • Middle Aged
  • Multiple Myeloma / blood
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / mortality
  • Platelet Count
  • Protease Inhibitors / adverse effects
  • Protease Inhibitors / therapeutic use*
  • Pyrazines / adverse effects
  • Pyrazines / therapeutic use*
  • Recurrence
  • Survival Rate

Substances

  • Antineoplastic Agents
  • Boronic Acids
  • Protease Inhibitors
  • Pyrazines
  • Bortezomib
  • Dexamethasone