Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America

N Engl J Med. 2007 Nov 22;357(21):2133-42. doi: 10.1056/NEJMoa070596.

Abstract

Background: Lenalidomide, an oral immunomodulatory drug that is similar to thalidomide but has a different safety profile, has clinical activity in relapsed or refractory multiple myeloma.

Methods: Patients in the United States and Canada who had received at least one previous therapy for multiple myeloma but who required additional treatment were randomly assigned to receive either 25 mg of lenalidomide or placebo on days 1 to 21 of a 28-day cycle. Both groups also received 40 mg of oral dexamethasone on days 1 to 4, 9 to 12, and 17 to 20 for the first four cycles. After the fourth cycle, 40 mg of dexamethasone was administered only on days 1 to 4. Safety, clinical response, time to progression, and overall survival were assessed.

Results: We assigned 177 patients to the lenalidomide group and 176 to the placebo group. Complete, near-complete, or partial responses occurred in 108 patients (61.0%) in the lenalidomide group and in 35 patients (19.9%) in the placebo group (P<0.001); complete responses occurred in 14.1% and 0.6%, respectively (P<0.001). The median time to progression was 11.1 months in the lenalidomide group and 4.7 months in the placebo group (P<0.001). Median overall survival times in the two groups were 29.6 months and 20.2 months, respectively (P<0.001). Grade 3 or 4 adverse events were reported in 85.3% of the lenalidomide group and in 73.1% of the placebo group; these events resulted in study discontinuation in 19.8% and 10.2%, respectively. Grade 3 or 4 neutropenia and venous thromboembolism were more common in the lenalidomide group than in the placebo group (41.2% vs. 4.6% and 14.7% vs. 3.4%, respectively; P<0.001 for both comparisons).

Conclusions: Lenalidomide plus dexamethasone is superior to placebo plus dexamethasone in patients with relapsed or refractory multiple myeloma. (ClinicalTrials.gov number, NCT00056160 [ClinicalTrials.gov].).

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Dexamethasone / therapeutic use*
  • Disease Progression
  • Double-Blind Method
  • Female
  • Glucocorticoids / therapeutic use*
  • Humans
  • Immunologic Factors / therapeutic use*
  • Lenalidomide
  • Male
  • Middle Aged
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / mortality
  • Recurrence
  • Survival Analysis
  • Thalidomide / adverse effects
  • Thalidomide / analogs & derivatives*
  • Thalidomide / therapeutic use

Substances

  • Glucocorticoids
  • Immunologic Factors
  • Thalidomide
  • Dexamethasone
  • Lenalidomide

Associated data

  • ClinicalTrials.gov/NCT00056160