Continuous lenalidomide treatment for newly diagnosed multiple myeloma

N Engl J Med. 2012 May 10;366(19):1759-69. doi: 10.1056/NEJMoa1112704.

Abstract

Background: Lenalidomide has tumoricidal and immunomodulatory activity against multiple myeloma. This double-blind, multicenter, randomized study compared melphalan-prednisone-lenalidomide induction followed by lenalidomide maintenance (MPR-R) with melphalan-prednisone-lenalidomide (MPR) or melphalan-prednisone (MP) followed by placebo in patients 65 years of age or older with newly diagnosed multiple myeloma.

Methods: We randomly assigned patients who were ineligible for transplantation to receive MPR-R (nine 4-week cycles of MPR followed by lenalidomide maintenance therapy until a relapse or disease progression occurred [152 patients]) or to receive MPR (153 patients) or MP (154 patients) without maintenance therapy. The primary end point was progression-free survival.

Results: The median follow-up period was 30 months. The median progression-free survival was significantly longer with MPR-R (31 months) than with MPR (14 months; hazard ratio, 0.49; P<0.001) or MP (13 months; hazard ratio, 0.40; P<0.001). Response rates were superior with MPR-R and MPR (77% and 68%, respectively, vs. 50% with MP; P<0.001 and P=0.002, respectively, for the comparison with MP). The progression-free survival benefit associated with MPR-R was noted in patients 65 to 75 years of age but not in those older than 75 years of age (P=0.001 for treatment-by-age interaction). After induction therapy, a landmark analysis showed a 66% reduction in the rate of progression with MPR-R (hazard ratio for the comparison with MPR, 0.34; P<0.001) that was age-independent. During induction therapy, the most frequent adverse events were hematologic; grade 4 neutropenia was reported in 35%, 32%, and 8% of the patients in the MPR-R, MPR, and MP groups, respectively. The 3-year rate of second primary tumors was 7% with MPR-R, 7% with MPR, and 3% with MP.

Conclusions: MPR-R significantly prolonged progression-free survival in patients with newly diagnosed multiple myeloma who were ineligible for transplantation, with the greatest benefit observed in patients 65 to 75 years of age. (Funded by Celgene; MM-015 ClinicalTrials.gov number, NCT00405756.).

Publication types

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

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Disease-Free Survival
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Induction Chemotherapy
  • Kaplan-Meier Estimate
  • Lenalidomide
  • Maintenance Chemotherapy
  • Male
  • Melphalan / administration & dosage*
  • Melphalan / adverse effects
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / mortality
  • Neoplasms, Second Primary / epidemiology
  • Neutropenia / chemically induced
  • Prednisone / administration & dosage*
  • Prednisone / adverse effects
  • Thalidomide / administration & dosage
  • Thalidomide / adverse effects
  • Thalidomide / analogs & derivatives*

Substances

  • Thalidomide
  • Lenalidomide
  • Melphalan
  • Prednisone

Associated data

  • ClinicalTrials.gov/NCT00405756