A Phase 2 Study of Bortezomib in Relapsed, Refractory Myeloma

N Engl J Med. 2003 Jun 26;348(26):2609-17. doi: 10.1056/NEJMoa030288.

Abstract

Background: Bortezomib, a boronic acid dipeptide, is a novel proteasome inhibitor that has been shown in preclinical and phase 1 studies to have antimyeloma activity.

Methods: In this multicenter, open-label, nonrandomized, phase 2 trial, we enrolled 202 patients with relapsed myeloma that was refractory to the therapy they had received most recently. Patients received 1.3 mg of bortezomib per square meter of body-surface area twice weekly for 2 weeks, followed by 1 week without treatment, for up to eight cycles (24 weeks). In patients with a suboptimal response, oral dexamethasone (20 mg daily, on the day of and the day after bortezomib administration) was added to the regimen. The response was evaluated according to the criteria of the European Group for Blood and Marrow Transplantation and confirmed by an independent review committee.

Results: Of 193 patients who could be evaluated, 92 percent had been treated with three or more of the major classes of agents for myeloma, and in 91 percent, the myeloma was refractory to the therapy received most recently. The rate of response to bortezomib was 35 percent, and those with a response included 7 patients in whom myeloma protein became undetectable and 12 in whom myeloma protein was detectable only by immunofixation. The median overall survival was 16 months, with a median duration of response of 12 months. Grade 3 adverse events included thrombocytopenia (in 28 percent of patients), fatigue (in 12 percent), peripheral neuropathy (in 12 percent), and neutropenia (in 11 percent). Grade 4 events occurred in 14 percent of patients.

Conclusions: Bortezomib, a member of a new class of anticancer drugs, is active in patients with relapsed multiple myeloma that is refractory to conventional chemotherapy.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Boronic Acids / adverse effects
  • Boronic Acids / therapeutic use*
  • Bortezomib
  • Cysteine Endopeptidases
  • Dexamethasone / therapeutic use
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Hemoglobins / analysis
  • Humans
  • Male
  • Middle Aged
  • Multienzyme Complexes / antagonists & inhibitors*
  • Multiple Myeloma / drug therapy*
  • Peripheral Nervous System Diseases / chemically induced
  • Prognosis
  • Protease Inhibitors / adverse effects
  • Protease Inhibitors / therapeutic use*
  • Proteasome Endopeptidase Complex
  • Pyrazines / adverse effects
  • Pyrazines / therapeutic use*
  • Recurrence

Substances

  • Antineoplastic Agents
  • Boronic Acids
  • Hemoglobins
  • Multienzyme Complexes
  • Protease Inhibitors
  • Pyrazines
  • Bortezomib
  • Dexamethasone
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex