Abstract
In newly diagnosed multiple myeloma (MM) patients, the combination melphalan, prednisone and thalidomide induces a fast tumor response with a high complete remission rate. In a prospective randomized trial, we compare the efficacy and toxicity of oral MPT and MP.
An interim analysis was conducted after the first 200 newly diagnosed myeloma patients, median age 72, range 56–85, entered the study, between January 2002 and June 2004. At present, 116 patients were evaluated for toxicity and 102 patients for response on an intent to treat basis. The MPT regimen included 6 monthly courses of oral melphalan 4 mg/sqm and prednisone 40 mg/sqm for 7 days every month plus thalidomide 100 mg/day continuously until any sign of progressive disease or relapse. The dose of thalidomide was reduced to 50% when grade II toxicity occurred, and suspended for any grade III. On December 2003, the protocol was amended and enoxaparin prophilaxys was added. The MP regimen was as MPT without thalidomide. The end points of the study were: response, EFS, OS and toxicity.
The response rate among patients who received MPT was: 25.9% immunofixation negative CR (CR), 5.5% immunofixation positive near CR (nCR) 48.2% partial remission (PR) (M-protein reduction 50–99%), 9.3% stable disease (SD) (M-protein reduction 0–49%) and 11.1% progressive disease (PD). The response rate after MP was 4.2% CR, 0% nCR, 43.6% PR, 23% SD and 29.2% PD. Response was followed by significant improvement of performance status, skeletal pain, anemia and transfusion requirement.
After a median follow up of 15 months, 38 patients relapsed: 11 (29%) after MPT and 27 (71%) after MP. The EFS @ 26 months was 67.8% for MPT and 32.4% for MP (P <0.001). The median OS has not been reached.
Treatment-related mortality was 5% after MPT (1 septicemia, 1 pulmonary thrombo-embolism and 1 heart failure), and 1.9% after MP (1 myocardial infarction). The major adverse events of MPT vs MP were: deep-vein thrombosis (19.3% vs 1.9%), grade III-IV infections (12.9% vs 1.9%), grade I-II neurotoxicity (35.5% vs 5.5%), grade III-IV hematologic toxicity (22.6% vs 27.6%). Thalidomide discontinuation was recorded in 33.8% of patients (8 thrombo-embolic events, 4 neurotoxicities, 4 constipations, 2 infections, 3 miscellaneous); dose-reduction in 24.2% of patients (8 neurotoxicities, 3 constipations, 4 miscellaneous).
MPT significantly improves response rate and EFS in elderly myeloma patients with a median age of 72 years. These results are similar to those observed after transplant.
An update of these data will be presented.
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