Oral melphalan, prednisone and thalidomide for newly diagnosed myeloma patients

Abstract

6549 Background: Thalidomide (T) alone or in combination has been tested and proved effective in multiple myeloma. No data are available on the association of T with oral Melphalan and Prednisone (MP) in newly diagnosed patients. Here, we evaluated the potential additive and synergistic effect of the combination Melphalan, Prednisone and Thalidomide (MPT) Methods: Between June 2002 and June 2003, 42 patients (median age 72, range 61–80) with newly diagnosed symptomatic multiple myeloma received 6 courses of MP (melphalan 4 mg/sqm and prednisone 40 mg/sqm for 7 days every month) plus T 100 mg/day continuously until any sign of disease progression or relapse. The dose of T was reduced to 50% when grade 2 WHO toxicity occurred, and suspended for any grade 3. All patients have completed the 6 assigned MP courses and were evaluated for both toxicity and response rate. Results: T increased the hematologic toxicity induced by MP: grade 3–4 WHO neutropenia was observed in 14% of patients. Constipation occurred in 28% of patients. Neurological toxicity was recorded in 38% of patients. The major acute adverse events were infections (26%) and deep-vein thrombosis (19%). One patient died for septicemia, and one for pulmonary thromboembolism. T discontinuation was required in 36% of patients (thromboembolic event, infection, costipation, hematologic toxicity). After treatment, partial responses (myeloma protein reduction >50%) were observed in 93% of patients, no responses (myeloma protein reduction <50%) in 7%. Complete remissions (disappearance of monoclonal protein and negative immunofixation) were 26%, near complete remissions (disappearance of monoclonal protein and positive immunofixation) were 19%, responses with myeloma protein reduction 90–99% were 12%. Time required to obtain the maximum response was 4 months in 88% of patients. Conclusions: The incidence of infections and deep-vein thrombosis was high, suggesting the need for antibiotic and anticoagulant prophylaxis. MPT induced a response rate significantly higher in comparison with any other conventional chemotherapy program. The CR rate was similar to those observed after transplant. No significant financial relationships to disclose.