Phase 2 study of arsenic trioxide in patients with relapsed or refractory multiple myeloma

Summary Despite aggressive and innovative therapy, patients with multiple myeloma (MM) invariably relapse and die of their disease. New options for non‐cytotoxic salvage therapy and additional therapeutic strategies are needed. Arsenic trioxide, an antitumour agent with a multifaceted mechanism of action, induces apoptosis in vitro in MM cell lines and freshly isolated cells from MM patients and, in preliminary studies, displayed clinical activity in patients with late‐stage MM. A phase 2, multicentre, open‐label study of arsenic trioxide was conducted in 24 MM patients; eight had relapsed and 16 were refractory to prior therapy. Patients received arsenic trioxide 0·25 mg/kg/d for 5 d/week during the first 2 weeks of each 4‐week cycle. Sixteen patients had grade 3 or 4 neutropenia and one required antibiotics. Reductions (25% or more) in serum M‐protein levels occurred in eight of 24 (33%) patients. An additional six (25%) patients had stable disease. The median time to response was 67·5 d, with a median duration of response of 130 d. Arsenic trioxide therapy lowered serum creatinine levels in two patients with high baseline values. These data indicate that arsenic trioxide is active and reasonably well tolerated as a single‐agent salvage therapy, even in patients with late‐stage, relapsed and refractory MM.