The Intergroupe Francophone du My?lome (IFM) has conducted studies of lenalidomid for the treatment of newly diagnosed multiple myeloma . Updated data from the IFM under the sponsorship of the University Hospital of Toulouse were presented at the 52nd Annual Meeting of the American Society of Hematology in Orlando (December 4 ? 7, 2010).
In this international Phase III, controlled, double-blind, multi-centre study, newly diagnosed multiple myeloma patients who achieved at least stable disease (SD) following autologous stem cell transplant (ASCT) were randomized to receive a two-month consolidation regimen of lenalidomid (Revlimid ?, Celgene International S?rl) monotherapy 25 mg per day on 21/28 days, followed by continuous daily treatment with either lenalidomide 10-15 mg (n=307) or placebo (n=307) until relapse.
While thalidomide has changed the treatment paradigm of patients with MM, its efficacy has been compromised by significant side effects. Immunomodulators (IMiDs) such as lenalidomid, a second-generation structural and functional analogs of thalidomide, are specifically designed to enhance anticancer properties and better tolerability profiles. [1]
When compared to thalidomide, lenalidomid exhibits a greatly enhanced potency for immunomodulation and antiangiogenesis. In clinical studies, immunomodulators (IMiDs) appear to have reduced sedative and neurotoxicity effects, which are often associated with long-term thalidomide dosing.[2]
Patients receiving continuous lenalidomide following ASCT had a median progression free survival period of 42 months from randomization compared to 24 months (HR=0.50, p<0.10-8) for patients that received placebo.[3] This represented a 50% reduction in risk of disease progression for patients receiving continuous lenalidomide. Five-year overall survival was 81% for both arms of the study at the time of reporting. According to the study, a longer follow-up is required to appreciate the impact on overall survival.
Clinically significant improvements in progression free survival were independent of prior induction therapy, depth of response after ASCT, disease volume (expressed by beta-2 microglobulin) or myeloma with high risk cytogenetic features (deletion 13) at entry into the study.
The most common grade 3-4 adverse events experienced by patients receiving lenalidomide or placebo in the study were neutropenia (43% vs. 14%, respectively), thrombocytopenia (12% vs. 6%) and infections (10% vs. 5%). The IFM data are from an investigational study. lenalidomid is not approved as a treatment for patients newly diagnosed with multiple myeloma.
For more information:
References:
[1] Srkalovic G, Hussein M. Immunomodulatory compounds (IMiDs) in the treatment of multiple myeloma. Bosn J Basic Med Sci. 2009 Oct;9 Suppl 1:3-10
[2] Knight R IMiDs: a novel class of immunomodulators. Semin Oncol.2005 Aug;32(4 Suppl 5):S24-30.
[3] Frontline Therapy with Bortezomib, Lenalidomide, and Dexamethasone (VRD) Induction Followed by Autologous Stem Cell Transplantation, VRD Consolidation and Lenalidomide Maintenance In Newly Diagnosed Multiple Myeloma Patients: Primary Results of the IFM 2008 Phase II Study ?[Abstract 624] 52nd Annual Meeting of the American Society of Hematology in Orlando (December 4 ? 7, 2010).
