Antitumor activity of thalidomide in refractory multiple myeloma.

Background: Patients with myeloma who relapse after high-dose chemotherapy have few therapeutic options. Since increased bone marrow vascularity impar ts a poor prognosis in myeloma, we evaluated the efficacy of thalidomide, w hich has antiangiogenic properties, in patients with refractory disease. Methods: Eighty-four previously treated patients with refractory myeloma (7 6 with a relapse after high-dose chemotherapy) received oral thalidomide as a single agent for a median of 80 days (range, 2 to 465). The starting dos e was 200 mg daily, and the dose was increased by 200 mg every two weeks un til it reached 800 mg per day. Response was assessed on the basis of a redu ction of the myeloma protein in serum or Bence Jones protein in urine that lasted for at least six weeks. Results: The serum or urine levels of paraprotein were reduced by at least 90 percent in eight patients (two had a complete remission), at least 75 pe rcent in six patients, at least 50 percent in seven patients, and at least 25 percent in six patients, for a total rate of response of 32 percent. Red uctions in the paraprotein levels were apparent within two months in 78 per cent of the patients with a response and were associated with decreased num bers of plasma cells in bone marrow and increased hemoglobin levels. The mi crovascular density of bone marrow did not change significantly in patients with a response. At least one third of the patients had mild or moderate c onstipation, weakness or fatigue, or somnolence. More severe adverse effect s were infrequent (occurring in less than 10 percent of patients), and hema tologic effects were rare. As of the most recent follow-up, 36 patients had died (30 with no response and 6 with a response). After 12 months of follo w-up, Kaplan-Meier estimates of the mean (+/-SE) rates of event-free surviv al and overall survival for all patients were 22+/-5 percent and 58+/-5 per cent, respectively. Conclusions: Thalidomide is active against advanced myeloma. It can induce marked and durable responses in some patients with multiple myeloma, includ ing those who relapse after high-dose chemotherapy. (N Engl J Med 1999;341: 1565-71.) (C) 1999, Massachusetts Medical Society.