PHASE I-II EVALUATION OF RAPID-SEQUENCE TANDEM HIGH-DOSE MELPHALAN WITH PERIPHERAL-BLOOD STEM-CELL SUPPORT IN PATIENTS WITH MULTIPLE-MYELOMA

This study was designed to determine the maximum tolerated dose (MTD) of high-dose melphalan (HDM), with peripheral blood stem cell support, that could be given twice within 90 days to patients with multiple my eloma, Twenty patients received tandem HDM at 160, 180 or 200 mg/m(2) and a total of 55 were treated at the estimated MTD of 200 mg/m2. Seve nteen of 55 (31%) did not receive cycle 2; six because of low CD34(+) cell yields, three because of severe (n = 1) or fatal toxicities (n = 2) and eight for other reasons, The median interval between doses for 38 patients was 70 days (range 41-225), Three of 55 patients (5%) died of treatment-related causes, In patients completing two cycles of HDM , at any dose level, the complete remission rate improved from 15% fol lowing cycle 1 to 55% following cycle 2, The probabilities of survival , event-free survival and relapse or progression at 18 months for the 55 patients treated at the MTD were 0.84, 0.76 and 0.20, respectively, with a median follow-up of 19 months (range 9-36) from mobilization c hemotherapy, It was concluded that two cycles of HDM, 200 mg/m(2), cou ld be administered to approximately 70% of patients under the age of 6 6 with multiple myeloma in a median interval of 70 days, with improvem ent in CR rates.