Lenalidomide maintenance after stem-cell transplantation for multiple myeloma.

Abstract

BACKGROUND:

High-dose chemotherapy with autologous stem-cell transplantation is a standard treatment for young patients with multiple myeloma. Residual disease is almost always present after transplantation and is responsible for relapse. This phase 3, placebo-controlled trial investigated the efficacy of lenalidomide maintenance therapy after transplantation.

METHODS:

We randomly assigned 614 patients younger than 65 years of age who had nonprogressive disease after first-line transplantation to maintenance treatment with either lenalidomide (10 mg per day for the first 3 months, increased to 15 mg if tolerated) or placebo until relapse. The primary end point was progression-free survival.

RESULTS:

Lenalidomide maintenance therapy improved median progression-free survival (41 months, vs. 23 months with placebo; hazard ratio, 0.50; P<0.001). This benefit was observed across all patient subgroups, including those based on the β(2)-microglobulin level, cytogenetic profile, and response after transplantation. With a median follow-up period of 45 months, more than 70% of patients in both groups were alive at 4 years. The rates of grade 3 or 4 peripheral neuropathy were similar in the two groups. The incidence of second primary cancers was 3.1 per 100 patient-years in the lenalidomide group versus 1.2 per 100 patient-years in the placebo group (P=0.002). Median event-free survival (with events that included second primary cancers) was significantly improved with lenalidomide (40 months, vs. 23 months with placebo; P<0.001).

CONCLUSIONS:

Lenalidomide maintenance after transplantation significantly prolonged progression-free and event-free survival among patients with multiple myeloma. Four years after randomization, overall survival was similar in the two study groups. (Funded by the Programme Hospitalier de Recherche Clinique and others; ClinicalTrials.gov number, NCT00430365.).

• Authors: Michel Attal, Valerie Lauwers-Cances, Gerald Marit, Denis Caillot, Philippe Moreau, Thierry Facon, Anne Marie Stoppa, Cyrille Hulin, Lofti Benboubker, Laurent Garderet, Olivier Decaux, Serge Leyvraz, Marie-Christiane Vekemans, Laurent Voillat, Mauricette Michallet, Brigitte Pegourie, Charles Dumontet, Murielle Roussel, Xavier Leleu, Claire Mathiot, Catherine Payen, Hervé Avet-Loiseau, Jean-Luc Harousseau, IFM Investigators
• Journal: The New England journal of medicine (N Engl J Med) Vol. 366 Issue 19 Pg. 1782-91 (May 10 2012) ISSN: 1533-4406 [Electronic] United States
• PMID: 22571202 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Thalidomide
• Lenalidomide

Topics

• Adult
• Aged
• Antineoplastic Agents (adverse effects, therapeutic use)
• Disease-Free Survival
• Double-Blind Method
• Female
• Follow-Up Studies
• Humans
• Kaplan-Meier Estimate
• Lenalidomide
• Maintenance Chemotherapy
• Male
• Middle Aged
• Multiple Myeloma (drug therapy, mortality)
• Neoplasms, Second Primary (epidemiology)
• Stem Cell Transplantation
• Thalidomide (adverse effects, analogs & derivatives, therapeutic use)
• Young Adult