Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma.

Abstract

BACKGROUND:

The combination melphalan-prednisone-thalidomide (MPT) is considered a standard therapy for patients with myeloma who are ineligible for stem-cell transplantation. However, emerging data on the use of lenalidomide and low-dose dexamethasone warrant a prospective comparison of the two approaches.

METHODS:

We randomly assigned 1623 patients to lenalidomide and dexamethasone in 28-day cycles until disease progression (535 patients), to the same combination for 72 weeks (18 cycles; 541 patients), or to MPT for 72 weeks (547 patients). The primary end point was progression-free survival with continuous lenalidomide-dexamethasone versus MPT.

RESULTS:

The median progression-free survival was 25.5 months with continuous lenalidomide-dexamethasone, 20.7 months with 18 cycles of lenalidomide-dexamethasone, and 21.2 months with MPT (hazard ratio for the risk of progression or death, 0.72 for continuous lenalidomide-dexamethasone vs. MPT and 0.70 for continuous lenalidomide-dexamethasone vs. 18 cycles of lenalidomide-dexamethasone; P<0.001 for both comparisons). Continuous lenalidomide-dexamethasone was superior to MPT for all secondary efficacy end points, including overall survival (at the interim analysis). Overall survival at 4 years was 59% with continuous lenalidomide-dexamethasone, 56% with 18 cycles of lenalidomide-dexamethasone, and 51% with MPT. Grade 3 or 4 adverse events were somewhat less frequent with continuous lenalidomide-dexamethasone than with MPT (70% vs. 78%). As compared with MPT, continuous lenalidomide-dexamethasone was associated with fewer hematologic and neurologic toxic events, a moderate increase in infections, and fewer second primary hematologic cancers.

CONCLUSIONS:

As compared with MPT, continuous lenalidomide-dexamethasone given until disease progression was associated with a significant improvement in progression-free survival, with an overall survival benefit at the interim analysis, among patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation. (Funded by Intergroupe, Francophone du Myélome and Celgene; FIRST ClinicalTrials.gov number, NCT00689936; European Union Drug Regulating Authorities Clinical Trials number, 2007-004823-39.).

• Authors: Lotfi Benboubker, Meletios A Dimopoulos, Angela Dispenzieri, John Catalano, Andrew R Belch, Michele Cavo, Antonello Pinto, Katja Weisel, Heinz Ludwig, Nizar Bahlis, Anne Banos, Mourad Tiab, Michel Delforge, Jamie Cavenagh, Catarina Geraldes, Je-Jung Lee, Christine Chen, Albert Oriol, Javier de la Rubia, Lugui Qiu, Darrell J White, Daniel Binder, Kenneth Anderson, Jean-Paul Fermand, Philippe Moreau, Michel Attal, Robert Knight, Guang Chen, Jason Van Oostendorp, Christian Jacques, Annette Ervin-Haynes, Hervé Avet-Loiseau, Cyrille Hulin, Thierry Facon, FIRST Trial Team
• Journal: The New England journal of medicine (N Engl J Med) Vol. 371 Issue 10 Pg. 906-17 (Sep 04 2014) ISSN: 1533-4406 [Electronic] United States
• PMID: 25184863 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Thalidomide
• Dexamethasone
• Lenalidomide
• Melphalan
• Prednisone

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Dexamethasone (administration & dosage, adverse effects)
• Disease-Free Survival
• Female
• Humans
• Kaplan-Meier Estimate
• Lenalidomide
• Male
• Melphalan (administration & dosage)
• Middle Aged
• Multiple Myeloma (drug therapy, immunology)
• Prednisone (administration & dosage)
• Thalidomide (administration & dosage, adverse effects, analogs & derivatives)