Use of melphalan,thalidomide, and dexamethasone in treatment of refractory and relapsed multiple myeloma

Twenty-one patients with relapsed and refractory Durie-Salmon stage III multiple myeloma who had either failed at least three previous regimens or presented with poor performance status, neutropenia, or thrombocytopenia were treated with up to four cycles of combination melphalan (50 mg intravenously), thalidomide (titrated to target of 400 mg orally daily), and dexamethasone (40 mg/day orally on d 1 to 4) every 4-6 wk. Maintenance treatment consisting of daily thalidomide and monthly dexamethasone was continued until disease progression. Although generally tolerated, combination melphalan/thalidomide/dexamethasone produced grade 4 neutropenia and thrombocytopenia in 52% and 38% of patients, respectively. Grade 3 nonhematologic toxicities included fatigue (14% of patients), neuropathy/paresthesia (5%), and nausea (5%). Four patients died while on therapy: two from neutropenic complications and two from progressive disease. Melphalan/ thalidomide/dexamethasone was highly active in this poor prognosis population: Serum monoclonal protein reductions > or = 25% occurred in 14 (70%) of 20 evaluable patients, including 1 patient with a complete response and 2 (13%) patients with reductions of 96%. Median progression-free-survival was 270 d (range: 73 to > 787 d) and median overall survival was 382 d. Median progression-free survival (> 420 d) has not been reached among patients responding to melphalan/thalidomide/dexamethasone. These results show that melphalan/thalidomide/dexamethasone therapy is active and generally tolerated in heavily pretreated multiple myeloma patients whose prognosis is otherwise poor.