Salvage therapy with thalidomide for patients with advanced relapsed/refractory multiple myeloma

Extensive introduction of high-dose therapy with stem cell support has significantly improved the outcome of patients with multiple myeloma (MM) in terms of increased complete remission (CR) rate and extended survival, both disease-free and overall. Few options, however, are presently available for primary refractory patients or patients who relapse after single or double autologous transplantation. Thalidomide, a glutamic acid derivative with anti-angiogenetic properties, has been recently proposed as salvage treatment for such patients. At our Insitution, we have started a therapeutic trial using thalidomide in relapsed/refractory MM patients. From October 1999 to July 2000, 27 patients (17M/1 OF) have been enrolled in the trial, the median age was 60 years, all patients were in stage HI, median b2 microglobulin was 4.36 mg/L, median bone marrow plasma cell infiltration was 70%, 13 patients had been previously submitted to one (n=4) or two (n=9) autologous stem cell transplant, one patient was treated in relapse after allogeneic stem cell transplant. Thalidomide was initially administered at 1 OOmg/day; if well tolerated, the dose was increased serially by 200mg every other week to a maximum of 800mg/day. Median administered dose was 400mg/day. WHO grade > II toxic effects were constipation (40%), lethargy (26%) and skin rash (20%) At present, 20 patients are évaluable for response, 5 (25%) showed more than 50% reduction in serum or urine M protein and 4 (20%) showed a greater than 25% response. After 5 months median follow-up, 4/9 patients are alive and progressionfree, 4 patients have relapsed, 1 patient died of pulmonary oedema while still in partial remission. These data confirm that thalidomide is active in relapsed/refractory MM and could thus deserve further testing, also in combination therapy, eventually as part of frontline treatment programmes.