Standard chemotherapy compared with high-dose chemoradiotherapy for multiple myeloma: final results of phase III US Intergroup Trial S9321

J Clin Oncol. 2006 Feb 20;24(6):929-36. doi: 10.1200/JCO.2005.04.5807. Epub 2006 Jan 23.

Abstract

Purpose: Results of a prospective randomized trial conducted by the Intergroupe Francais du Myélome (IFM 90) indicated that autologous hematopoietic cell-supported high-dose therapy (HDT) effected higher complete response rates and extended progression-free survival (PFS) and overall survival (OS) compared with standard-dose therapies (SDT) for patients with multiple myeloma (MM).

Patients and methods: In 1993, three North American cooperative groups launched a prospective randomized trial (S9321) comparing HDT (melphalan [MEL] 140 mg/m2 plus total-body irradiation 12 Gy) with SDT using the vincristine, carmustine, MEL, cyclophosphamide, and prednisone regimen. Responders on both arms (> or = 75%) were randomly assigned to interferon (IFN) or no maintenance treatment.

Results: With a median follow-up time of 76 months, no differences were observed in response rates between the two study arms (HDT, n = 261 patients; SDT, n = 255 patients). Similarly, PFS and OS durations did not differ between the HDT and SDT arms, with 7-year estimates of PFS of 17% and 16%, respectively, and OS of 37% and 42%, respectively. Of 242 patients achieving at least 75% tumor reduction, no difference was observed in PFS or OS among the 121 patients randomly assigned to IFN and the 121 patients randomly assigned to no maintenance therapy. Among 157 patients relapsing on SDT, 87 received a salvage autotransplantation; their median survival time of 30 months was only slightly better than the survival time of the remaining patients who were managed with further SDT (23 months; P = .13).

Conclusion: The HDT and SDT regimens used in S9321 yielded comparable response rates and PFS and OS durations. IFN maintenance therapy did not benefit patients who achieved > or = 75% tumor reduction on either arm.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bone Marrow Transplantation
  • Carmustine / administration & dosage
  • Chemotherapy, Adjuvant
  • Clinical Protocols
  • Cyclophosphamide / administration & dosage
  • Disease-Free Survival
  • Drug Administration Schedule
  • Female
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Interferons / administration & dosage
  • Male
  • Melphalan / administration & dosage
  • Middle Aged
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / radiotherapy*
  • Multiple Myeloma / surgery
  • Prednisone / administration & dosage
  • Prospective Studies
  • Radiotherapy, Adjuvant
  • Salvage Therapy / methods
  • Survival Analysis
  • Transplantation, Autologous
  • Transplantation, Homologous
  • Treatment Failure
  • Treatment Outcome
  • United States
  • Vincristine / administration & dosage
  • Whole-Body Irradiation

Substances

  • Vincristine
  • Cyclophosphamide
  • Interferons
  • Melphalan
  • Carmustine
  • Prednisone

Supplementary concepts

  • M-2 protocol

Grants and funding