title: Phase 3 trial of three thalidomide-containing regimens in patients with newly diagnosed multiple myeloma not transplant-eligible.
abstract: The introduction of agents such as thalidomide, lenalidomide, and bortezomib has changed the management of patients with multiple myeloma who are not eligible for autologous transplantation, many of whom are elderly. We sought to compare three thalidomide-based oral regimens among such patients in Latin America. We randomized patients with newly diagnosed multiple myeloma with measurable disease to one of the following regimens: melphalan, prednisone, and thalidomide (MPT); cyclophosphamide, thalidomide, and dexamethasone (CTD); and thalidomide and dexamethasone (TD). The TD arm was closed prematurely and was analyzed only descriptively. The primary endpoint was the overall response rate (ORR), whereas progression-free survival (PFS) and overall survival (OS) were secondary endpoints. The accrual rate was slower than expected, and the study was terminated after 82 patients had been randomized. The ORRs were 67.9 % with MPT, 89.7 % with CTD, and 68.7 % with TD (p = 0.056 for the comparison between MPT and CTD). The median PFS was 24.1 months for MPT, 25.9 months for CTD, and 21.5 months for TD. There were no statistically significant differences in PFS or OS between MPT and CTD. In an unplanned logistic regression analysis, ORR was significantly associated with treatment with CTD (p = 0.046) and with performance status of 0 or 1 (p = 0.035). Based on the current results, no definitive recommendations can be made regarding the comparative merit of the regimens tested. Nevertheless and until the results of further studies become available, we recommend either CTD or MPT as suitable frontline regimens for patients with multiple myeloma who are not candidates to transplantation in settings where lenalidomide and bortezomib are not available.
authors.affiliation: Department of Hematology and Oncology, Santa Casa de São Paulo Medical School, Rua Marquês de Itu, 579-3° andar, CEP 01223-001, São Paulo, Brazil. hungria@dialdata.com.br.
authors.forename: V T M
authors.initials: VT
authors.lastname: Hungria
authors.affiliation: Department of Hematology and Oncology, Santa Casa de São Paulo Medical School, Rua Marquês de Itu, 579-3° andar, CEP 01223-001, São Paulo, Brazil.
authors.forename: E Q
authors.initials: EQ
authors.lastname: Crusoé
authors.affiliation: Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: A
authors.initials: A
authors.lastname: Maiolino
authors.affiliation: Universidade Federal de Porto Alegre, Porto Alegre, Brazil.
authors.forename: R
authors.initials: R
authors.lastname: Bittencourt
authors.affiliation: Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
authors.forename: D
authors.initials: D
authors.lastname: Fantl
authors.affiliation: Liga Norte-Riograndense Contra o Câncer, Natal, Brazil.
authors.forename: J F R
authors.initials: JF
authors.lastname: Maciel
authors.affiliation: Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: R J
authors.initials: RJ
authors.lastname: Pessoa de Magalhaes
authors.affiliation: Department of Hematology and Oncology, Santa Casa de São Paulo Medical School, Rua Marquês de Itu, 579-3° andar, CEP 01223-001, São Paulo, Brazil.
authors.forename: M S S
authors.initials: MS
authors.lastname: Almeida
authors.affiliation: Department of Hematology and Oncology, Santa Casa de São Paulo Medical School, Rua Marquês de Itu, 579-3° andar, CEP 01223-001, São Paulo, Brazil.
authors.forename: P
authors.initials: P
authors.lastname: Cury
authors.affiliation: Department of Hematology and Oncology, Santa Casa de São Paulo Medical School, Rua Marquês de Itu, 579-3° andar, CEP 01223-001, São Paulo, Brazil.
authors.forename: F
authors.initials: F
authors.lastname: Hisgashi
authors.affiliation: Department of Hematology and Oncology, Santa Casa de São Paulo Medical School, Rua Marquês de Itu, 579-3° andar, CEP 01223-001, São Paulo, Brazil.
authors.forename: A L
authors.initials: AL
authors.lastname: Peres
authors.affiliation: Department of Hematology and Oncology, Santa Casa de São Paulo Medical School, Rua Marquês de Itu, 579-3° andar, CEP 01223-001, São Paulo, Brazil.
authors.forename: C S
authors.initials: CS
authors.lastname: Chiattone
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000188:drug therapy*; D013792:Thalidomide / Q000008:administration & dosage*; D014182:Transplantation, Autologous
chemical_list: D013792:Thalidomide
keywords: Autologous; Cyclophosphamide; Dexamethasone; Induction chemotherapy; Melphalan; Multiple myeloma; Survival analysis; Thalidomide; Transplantation