title: A phase II, single-arm, prospective study of bendamustine plus melphalan conditioning for second autologous stem cell transplantation in de novo multiple myeloma patients through a tandem transplant strategy.
abstract: This phase II trial evaluates, for the first time, the safety and efficacy of bendamustine plus high-dose melphalan (HDM) as a conditioning regimen before the second autologous stem cell transplantation (ASCT) in previously untreated multiple myeloma (MM) patients. In total, 32 ASCT patients received HDM (200 mg/m(2)) as conditioning for the first ASCT. After 3-6 months from the first ASCT, responding patients underwent a second ASCT following bendamustine (200 mg/m(2)) and HDM (140 mg/m(2)). High-dose chemotherapy and ASCT were performed with complete neutrophil and platelet recovery in all patients. The median number of days to neutrophil and platelet engraftment was 11 (range 9-15) and 12 (range 10-19), respectively. Only one subject experienced grade 3 diarrhea; the rate of mucositis and vomiting was significantly lower with the bendamustine plus HDM regimen compared with the HDM-only regimen (81.2 vs 96.9%, P=0.025 and 78.1 vs 100%, P=0.008). Overall response rate (ORR) was 81.2% after the first transplant, and 90.6% after the second, while complete response rates were 46.8 and 62.5%, respectively (P=0.016). Actuarial 2-year PFS and OS were 79% (95% confidence interval (CI), 60-98) and 97% (95% CI, 91-100), respectively. Bendamustine+HDM is feasible as the conditioning regimen for second ASCT in MM patients. The present study may pave the way for phase III studies specifically aimed at further investigating this combination strategy. The role of this combination in MM for conditioning regimen in a first or single ASCT setting should be also investigated.
authors.affiliation: Hematology and Stem Cell Transplantation Unit, Onco-Hematology Department, Azienda Ospedaliera 'BMM', Reggio Calabria, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Martino
authors.affiliation: National Research Council (CNR), Institute of Clinical Physiology, Reggio Calabria, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Tripepi
authors.affiliation: Hematology and Stem Cell Transplantation Unit, Onco-Hematology Department, Azienda Ospedaliera 'BMM', Reggio Calabria, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Messina
authors.affiliation: Hematology, Onco-Hematology Department, Azienda Ospedaliera 'BMM', Reggio Calabria, Italy.
authors.forename: I D
authors.initials: ID
authors.lastname: Vincelli
authors.affiliation: Hematology and Stem Cell Transplantation Unit, Onco-Hematology Department, Azienda Ospedaliera 'BMM', Reggio Calabria, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Console
authors.affiliation: Biotechnology Research Unit, Azienda Sanitaria Provinciale di Cosenza, Aprigliano (CS), Italy.
authors.forename: A G
authors.initials: AG
authors.lastname: Recchia
authors.affiliation: Haematology Unit, Azienda Ospedaliera Cosenza, Cosenza, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Gentile
authors.affiliation: Haematology Unit, Azienda Ospedaliera 'Pugliese-Ciaccio' Catanzaro, Catanzaro, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Molica
authors.affiliation: Biotechnology Research Unit, Azienda Sanitaria Provinciale di Cosenza, Aprigliano (CS), Italy.|Haematology Unit, Azienda Ospedaliera Cosenza, Cosenza, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Morabito
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069461:Bendamustine Hydrochloride / Q000008:administration & dosage*; D003967:Diarrhea / Q000139:chemically induced; D005260:Female; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage*; D008875:Middle Aged; D052016:Mucositis / Q000139:chemically induced; D009101:Multiple Myeloma / Q000150:complications / Q000188:drug therapy / Q000628:therapy*; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
chemical_list: D000069461:Bendamustine Hydrochloride; D008558:Melphalan