title: Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma.
abstract: Combinations of bortezomib (V) and dexamethasone (D) with either lenalidomide (R) or cyclophosphamide (C) have shown significant efficacy. This randomized phase 2 trial evaluated VDC, VDR, and VDCR in previously untreated multiple myeloma (MM). Patients received V 1.3 mg/m2 (days 1, 4, 8, 11) and D 40 mg (days 1, 8, 15), with either C 500 mg/m2 (days 1, 8) and R 15 mg (days 1-14; VDCR), R 25 mg (days 1-14; VDR), C 500 mg/m2 (days 1, 8; VDC) or C 500 mg/m2 (days 1, 8, 15; VDC-mod) in 3-week cycles (maximum 8 cycles), followed by maintenance with V 1.3 mg/m2 (days 1, 8, 15, 22) for four 6-week cycles (all arms)≥very good partial response was seen in 58%, 51%, 41%, and 53% (complete response rate of 25%, 24%, 22%, and 47%) of patients (VDCR, VDR, VCD, and VCD-mod, respectively); the corresponding 1-year progression-free survival was 86%, 83%, 93%, and 100%, respectively. Common adverse events included hematologic toxicities, peripheral neuropathy, fatigue, and gastrointestinal disturbances. All regimens were highly active and well tolerated in previously untreated MM, and, based on this trial, VDR and VCD-mod are preferred for clinical practice and further comparative testing. No substantial advantage was noted with VDCR over the 3-drug combinations. This trial is registered at www.clinicaltrials.gov (NCT00507442).
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA. kumar.shaji@mayo.edu
authors.forename: Shaji
authors.initials: S
authors.lastname: Kumar
authors.forename: Ian
authors.initials: I
authors.lastname: Flinn
authors.forename: Paul G
authors.initials: PG
authors.lastname: Richardson
authors.forename: Parameswaran
authors.initials: P
authors.lastname: Hari
authors.forename: Natalie
authors.initials: N
authors.lastname: Callander
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Noga
authors.forename: A Keith
authors.initials: AK
authors.lastname: Stewart
authors.forename: Francesco
authors.initials: F
authors.lastname: Turturro
authors.forename: Robert
authors.initials: R
authors.lastname: Rifkin
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Wolf
authors.forename: Jose
authors.initials: J
authors.lastname: Estevam
authors.forename: George
authors.initials: G
authors.lastname: Mulligan
authors.forename: Hongliang
authors.initials: H
authors.lastname: Shi
authors.forename: Iain J
authors.initials: IJ
authors.lastname: Webb
authors.forename: S Vincent
authors.initials: SV
authors.lastname: Rajkumar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D000069286:Bortezomib; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D020360:Neoadjuvant Therapy; D011719:Pyrazines / Q000008:administration & dosage* / Q000009:adverse effects; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone; D003520:Cyclophosphamide; D000077269:Lenalidomide