title: Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantation.
abstract: As part of the randomized MRC Myeloma IX trial, we compared an attenuated regimen of cyclophosphamide, thalidomide, and dexamethasone (CTDa; n = 426) with melphalan and prednisolone (MP; n = 423) in patients with newly diagnosed multiple myeloma ineligible for autologous stem-cell transplantation. The primary endpoints were overall response rate, progression-free survival, and overall survival (OS). The overall response rate was significantly higher with CTDa than MP (63.8% vs 32.6%; P < .0001), primarily because of increases in the rate of complete responses (13.1% vs 2.4%) and very good partial responses (16.9% vs 1.7%). Progression-free survival and OS were similar between groups. In this population, OS correlated with the depth of response (P < .0001) and favorable interphase fluorescence in situ hybridization profile (P < .001). CTDa was associated with higher rates of thromboembolic events, constipation, infection, and neuropathy than MP. In elderly patients with newly diagnosed multiple myeloma (median age, 73 years), CTDa produced higher response rates than MP but was not associated with improved survival outcomes. We highlight the importance of cytogenetic profiling at diagnosis and effective management of adverse events. This trial was registered at International Standard Randomized Controlled Trials Number as #68454111.
authors.affiliation: Institute of Cancer Research, Royal Marsden Hospital, London, United Kingdom. gareth.morgan@icr.ac.uk
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Morgan
authors.forename: Faith E
authors.initials: FE
authors.lastname: Davies
authors.forename: Walter M
authors.initials: WM
authors.lastname: Gregory
authors.forename: Nigel H
authors.initials: NH
authors.lastname: Russell
authors.forename: Sue E
authors.initials: SE
authors.lastname: Bell
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Szubert
authors.forename: Nuria
authors.initials: N
authors.lastname: Navarro Coy
authors.forename: Gordon
authors.initials: G
authors.lastname: Cook
authors.forename: Sylvia
authors.initials: S
authors.lastname: Feyler
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Byrne
authors.forename: Huw
authors.initials: H
authors.lastname: Roddie
authors.forename: Claudius
authors.initials: C
authors.lastname: Rudin
authors.forename: Mark T
authors.initials: MT
authors.lastname: Drayson
authors.forename: Roger G
authors.initials: RG
authors.lastname: Owen
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Ross
authors.forename: Graham H
authors.initials: GH
authors.lastname: Jackson
authors.forename: J Anthony
authors.initials: JA
authors.lastname: Child
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage* / Q000009:adverse effects; D004608:Eligibility Determination; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000628:therapy; D020360:Neoadjuvant Therapy; D018579:Patient Selection; D013792:Thalidomide / Q000008:administration & dosage* / Q000009:adverse effects; D014182:Transplantation, Autologous
chemical_list: D013792:Thalidomide; D003907:Dexamethasone; D003520:Cyclophosphamide