A Phase III Study to Determine the Efficacy and Safety of Lenalidomide in Combination with Melphalan and Prednisone (MPR) in Elderly Patients with Newly Diagnosed Multiple Myeloma.
Meletios A. Dimopoulos2,
Christian Jacques*,6 and
1 Division of Hematology, University of Torino, Torino, Italy, 2 Department of Clinical Therapeutics, Alexandra Hospital, University of Athens School of Medicine, Athens, Greece, 3 University Hospital Leuven, Leuven, Belgium, 4 Department of Medicine (Hematology/Oncology), University of Muenster, Muenster, Germany, 5 Division of Hematology, University, Rome, Italy, 6 Celgene Corporation, Summit, NJ, USA, 7 Haematology Dept and Dorevitch Pathology, Frankston Hospital, Frankston, Australia
Background: Lenalidomide (Revlimid®) is an oral immunomodulatory agentwith clinical efficacy in patients with multiple myeloma (MM).In patients with relapsed/refractory MM, lenalidomide plus dexamethasoneimproved time to progression (TTP) and overall survival (OS)in comparison with dexamethasone alone. In newly diagnosed MMpatients, the current study compares the efficacy and safetyof melphalan, prednisone and lenalidomide (MPR) with that ofMP alone.
Methods: Key inclusion criteria were: 65 years of age, newly diagnosedand symptomatic MM. 459 patients were randomly assigned to receiveMPR followed by lenalidomide maintenance therapy or MPR followedby placebo maintenance therapy or MP followed by placebo maintenancetherapy (Figure 1). The study induction and maintenance phaseswere followed by an open label lenalidomide extension and afollow-up phase. All patients received aspirin 100 mg/day asthrombo-prophylaxis. The primary endpoint of the study is progressionfree survival (PFS). The secondary endpoints are OS, time-to-progression,response rate, time to response, response duration, time-to-nextanti-myeloma therapy, safety, quality of life and exploratoryassessment of cytogenetic abnormalities. Primary comparisonis based on the intent-to-treat population comparing PFS betweenMPR followed by lenalidomide with MP followed by placebo; secondarycomparisons are between MPR followed by lenalidomide and MPRfollowed by placebo, and between MPR followed by placebo andMP followed by placebo.
Results: The first patient was enrolled in February 2007. A pre-plannedinterim analysis to evaluate the efficacy and safety was performedat 50% information. An independent central adjudication committeedetermined the assessment and timing of progressive diseaseprior to the interim analysis. At the interim analysis, it wasdetermined by the Data Monitoring Committee (DMC) that the studyhad crossed the O'Brien Fleming superiority boundary for theprimary endpoint, demonstrating a highly statistically significantimprovement in PFS for patients treated with MPR compared withMP as first-line treatment for MM patients. The topline resultswill be availabel at the time of the meeting.
Conclusions: MPR is an effective and safe regimen for front-line use in MM.PFS was significantly improved in patients who received MPRfollowed by lenalidomide maintenance compared with those whoreceived MP followed by placebo maintenance. MPR followed bylenalidomide maintenance is a new therapeutic option and canbe considered a new standard for patients older than 65 yearsold.
Disclosures:Palumbo:Celgene: Honoraria, Membership on an entity's Boardof Directors or advisory committees; Janssen Cilag: Honoraria,Membership on an entity's Board of Directors or advisory committees;Pharmion: Honoraria, Membership on an entity's Board of Directorsor advisory committees. Off Label Use: Lenalidomide is not approvedfor first line use in multiple myeloma. Dimopoulos:Celgene:Honoraria. Delforge:Janssen-Cilag: Consultancy, Honoraria;Celgene: Honoraria, Speakers Bureau. Kropff:Ortho Biotech:Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy,Honoraria, Speakers Bureau. Foa:Celgene: Membership on an entity'sBoard of Directors or advisory committees. Yu:Celgene: Employment.Herbein:Celgene: Employment. Mei:Celgene: Employment. Jacques:Celgene: Employment. Catalano:Celgene: Research Funding.
* Asterisk with author names denotes non-ASH members.