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Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma.

The New England journal of medicine (2014-09-04)
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
ABSTRACT

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. 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. 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. 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.).

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Dexamethasone, powder, BioReagent, suitable for cell culture, ≥97%
Sigma-Aldrich
Dexamethasone, ≥98% (HPLC), powder
Sigma-Aldrich
Dexamethasone-Water Soluble, BioReagent, suitable for cell culture
Sigma-Aldrich
Prednisone, ≥98%
Supelco
Dexamethasone, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Dexamethasone, powder, γ-irradiated, BioXtra, suitable for cell culture, ≥80% (HPLC)
Supelco
Prednisone, Pharmaceutical Secondary Standard; Certified Reference Material
USP
Prednisone, United States Pharmacopeia (USP) Reference Standard
Supelco
Dexamethasone solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®
Sigma-Aldrich
(±)-Thalidomide, ≥98%, powder
Sigma-Aldrich
Dexamethasone, meets USP testing specifications
Sigma-Aldrich
Melphalan, powder
Dexamethasone, European Pharmacopoeia (EP) Reference Standard
Supelco
Dexamethasone, VETRANAL®, analytical standard
Sigma-Aldrich
Dexamethasone, tested according to Ph. Eur.
Dexamethasone for system suitability, European Pharmacopoeia (EP) Reference Standard
Dexamethasone for peak identification, European Pharmacopoeia (EP) Reference Standard