title: High-dose therapy and autologous peripheral blood stem cell transplantation in multiple myeloma: up-front or rescue treatment? Results of a multicenter sequential randomized clinical trial.
abstract: Results to date indicate that high-dose therapy (HDT) with autologous stem cell support improves survival of patients with symptomatic multiple myeloma (MM). We performed a multicenter, sequential, randomized trial designed to assess the optimal timing of HDT and autotransplantation. 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 case of primary resistance to CCT or at relapse in responders. PBSC were collected before randomization, after mobilization by chemotherapy, and, in the two groups, HDT was preceded by three or four treatments with vincristine, doxorubicin, and methylprednisolone. Data were analyzed on an intent-to-treat basis using a sequential design. Within a median follow-up of 58 months, estimated median overall survival (OS) was 64.6 months in the early HDT group and 64 months in the late group. Survival curves were not different (P = .92, log-rank test). Median event-free survival (EFS) was 39 months in the early HDT group whereas median time between randomization and CCT failure was 13 months in the late group. Average time without symptoms, treatment, and treatment toxicity (TWiSTT) were 27.8 months (95% confidence interval [CI]; 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 exceeding 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 chemotherapy.
authors.affiliation: Immuno-Haematology Unit and the Department of Biostatistics, Hôpital Saint Louis, Paris; The Rheumatology and Haematology Units, Hôpital Cochin, Paris.
authors.forename: J P
authors.initials: JP
authors.lastname: Fermand
authors.forename: P
authors.initials: P
authors.lastname: Ravaud
authors.forename: S
authors.initials: S
authors.lastname: Chevret
authors.forename: M
authors.initials: M
authors.lastname: Divine
authors.forename: V
authors.initials: V
authors.lastname: Leblond
authors.forename: C
authors.initials: C
authors.lastname: Belanger
authors.forename: M
authors.initials: M
authors.lastname: Macro
authors.forename: E
authors.initials: E
authors.lastname: Pertuiset
authors.forename: F
authors.initials: F
authors.lastname: Dreyfus
authors.forename: X
authors.initials: X
authors.lastname: Mariette
authors.forename: C
authors.initials: C
authors.lastname: Boccacio
authors.forename: J C
authors.initials: JC
authors.lastname: Brouet
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015993:Life Tables; D008558:Melphalan / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000628:therapy*; D011241:Prednisone / Q000008:administration & dosage; D011344:Procarbazine / Q000008:administration & dosage; D012074:Remission Induction; D016879:Salvage Therapy; D016019:Survival Analysis; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D011344:Procarbazine; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D008558:Melphalan; D011241:Prednisone; D008727:Methotrexate