High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma

N Engl J Med. 2003 May 8;348(19):1875-83. doi: 10.1056/NEJMoa022340.

Abstract

Background: High-dose therapy with supporting autologous stem-cell transplantation remains a controversial treatment for cancer. In multiple myeloma, first-line regimens incorporating high-dose therapy yield higher remission rates than do conventional-dose treatments, but evidence that this translates into improved survival is limited.

Methods: In this multicenter study, the Medical Research Council Myeloma VII Trial, we randomly assigned 407 patients with previously untreated multiple myeloma who were younger than 65 years of age to receive either standard conventional-dose combination chemotherapy or high-dose therapy and an autologous stem-cell transplant.

Results: Among the 401 patients who could be evaluated, the rates of complete response were higher in the intensive-therapy group than in the standard-therapy group (44 percent vs. 8 percent, P<0.001). The rates of partial response were similar (42 percent and 40 percent, respectively; P=0.72), and the rates of minimal response were lower in the intensive-therapy group than in the standard-therapy group (3 percent vs. 18 percent, P<0.001). Intention-to-treat analysis showed a higher rate of overall survival (P=0.04 by the log-rank test) and progression-free survival (P<0.001) in the intensive-therapy group than in the standard-therapy group. As compared with standard therapy, intensive treatment increased median survival by almost 1 year (54.1 months [95 percent confidence interval, 44.9 to 65.2] vs. 42.3 months [95 percent confidence interval, 33.1 to 51.6]). There was a trend toward a greater survival benefit in the group of patients with a poor prognosis, as defined by a high beta2-microglobulin level (more than 8 mg per liter).

Conclusions: High-dose therapy with autologous stem-cell rescue is an effective first-line treatment for patients with multiple myeloma who are younger than 65 years of age.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Alkylating / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Carmustine / administration & dosage
  • Cause of Death
  • Combined Modality Therapy
  • Cyclophosphamide / administration & dosage
  • Doxorubicin / administration & dosage
  • Female
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Male
  • Melphalan / administration & dosage*
  • Middle Aged
  • Multiple Myeloma / drug therapy
  • Multiple Myeloma / mortality
  • Multiple Myeloma / therapy*
  • Prognosis
  • Survival Analysis

Substances

  • Antineoplastic Agents, Alkylating
  • Doxorubicin
  • Cyclophosphamide
  • Melphalan
  • Carmustine