HIGH-DOSE THERAPY AND AUTOLOGOUS PERIPHERAL-BLOOD STEM-CELL TRANSPLANTATION IN MULTIPLE-MYELOMA - UP-FRONT OR RESCUE TREATMENT - RESULTS OFA MULTICENTER SEQUENTIAL RANDOMIZED CLINICAL-TRIAL

Results to date indicate that high-dose therapy (HDT) with autologous stem cell support improves survival of patients with symptomatic multi ple myeloma (MM). We performed a multicenter, sequential, randomized t rial designed to assess the optimal timing of HDT and autotransplantat ion. Among 202 enrolled patients who were up to 56 years old, 185 were randomly assigned to receive HDT and peripheral blood stem cell (PBSC ) autotransplantation (early HDT group, n = 91) or a conventional-dose chemotherapy (CCT) regimen (late HDT group, n = 94). In the late HDT group, HDT and transplantation were performed as rescue treament, in c ase of primary resistance to CCT or at relapse in responders. PBSC wer e collected before randomization, after mobilization by chemotherapy, and, in the two groups, HDT was preceded by three or four treatments w ith vincristine, doxorubicin, and methylprednisolone. Data were analyz ed on an intent-to-treat basis using a sequential design. Within a med ian follow-up of 58 months, estimated median overall survival (OS) was 64.6 months in the early HDT group and 64 months in the rate group. S urvival curves were not different (P = .92, log-rank test). Median eve nt-free survival (EFS) was 39 months in the early HDT group whereas me dian time between randomization and CCT failure was 13 months in the l ate group. Average time without symptoms, treatment, and treatment tox icity (TWISTT) were 27.8 months (95% confidence interval [Cl]; range, 23.8 to 31.8) and 22.3 months (range, 16.0 to 28.6) in the two groups, respectively. HDT with PBSC transplantation obtained a median OS exce eding 5 years in young patients with symptomatic MM, whether performed early, as first-line therapy, or late, as rescue treatment. Early HDT may be preferred because it is associated with a shorter period of ch emotherapy. (C) 1998 by The American Society of Hematology.