Randomized Clinical Trial Comparing Melphalan-Prednisone (MP), MP-Thalidomide (MP-THAL) and High-Dose Therapy Using Melphalan 100 MG/M2 (MEL100) for Newly Diagnosed Myeloma Patients Aged 65–75 Years. Interim Analysis of the IFM 99-06 Trial on 350 Patients.

Abstract

Abstract The results of the IFM 95-01 trial comparing MP to Dexamethasone-based regimens were consistent with the fact that the standard MP remained the reference treatment for patients (pts) older than 65 years with multiple myeloma (MM) (Blood2003;102,147a). In May 2000, the IFM designed a new trial, IFM 99-06, for pts aged 65–75 years, comparing standard MP (12 courses at 6 weeks intervals) to MP-THAL (same MP, THAL at the maximum tolerated dose but ≤400 mg/day, stopped at the end of MP) and a MEL100-based treatment (intermediate-dose MEL procedure developped by the Italian MM study group); VADx2, cyclophosphamide 3g/m2 for stem cells collection, 2 courses of MEL100. IFM99-06 is planned to randomize 500 pts, according to a 3 (MP) - 2 (MP-THAL) - 2 (MEL100) allocation, and schedules two main comparisons ; MP vs MP-THAL and MP vs MEL100. The primary end point is overall survival. In the absence of clear toxicity data for MP-THAL and MEL100 in elderly MM pts, in the setting of a large randomized study, two interim analyses were planned, after the enrollment of 200 (40%) and 350 (70%) pts (followed at least 4 months), to be reviewed by an independent expert review committee (R.Schots / B.Van Camp, Brussels, Belgium ; M. Boccadoro, Torino, Italy ; S.Chevret, Paris-St-Louis, France). The first interim analysis was performed during the first months of 2003 (reference date for analysis January 2, 2003 ; 200 pts enrolled between May, 2000 and June, 2002). The experts considered that (i) the adverse events were as expected with the treatments used (ii) no clear-cut advantage or disadvantage of either MP-THAL or MEL100 over MP was observed according to the statistical rule of the first interim analysis (iii) the trial should pursue as planned. Following a request of the french regulatory agency AFSSAPS, we were asked to look rapidly at some thalidomide toxicities and at the feasability of MEL100. The incidence of deep veinous thrombosis (DVT) was 6%, 9% and 3.5% for MP, MP-THAL and MEL100, respectively (no toxic death due to DVT). Peripheral neuropathy was observed in 25% of MP-THAL pts (14/57 pts, at a median time of 12 months). MEL100 was feasible ; approximately 80% of the pts received the cyclophosphamide and 65% received the 2 MEL100 treatments. No toxic death was noted among 74 courses of MEL100 (39 pts). The second interim analysis, performed on 350 pts (382 pts enrolled on August 1, 2004) is in progress during July/August 2004 (date of point June 1, 2004). Results of the second interim analysis will be presented at the meeting.