title: Retrospective matched-pairs analysis of bortezomib plus dexamethasone versus bortezomib monotherapy in relapsed multiple myeloma.
abstract: Bortezomib-dexamethasone is widely used for relapsed myeloma in routine clinical practice, but comparative data versus single-agent bortezomib are lacking. This retrospective analysis compared second-line treatment with bortezomib-dexamethasone and bortezomib using 109 propensity score-matched pairs of patients treated in three clinical trials: MMY-2045, APEX, and DOXIL-MMY-3001. Propensity scores were estimated using logistic regression analyses incorporating 13 clinical variables related to drug exposure or clinical outcome. Patients received intravenous bortezomib 1.3 mg/m(2) on days 1, 4, 8, and 11, in 21-day cycles, alone or with oral dexamethasone 20 mg on the days of/after bortezomib dosing. Median bortezomib cumulative dose (27.02 and 28.60 mg/m(2)) and treatment duration (19.6 and 17.6 weeks) were similar with bortezomib-dexamethasone and bortezomib, respectively. The overall response rate was higher (75% vs. 41%; odds ratio=3.467; P<0.001), and median time-to-progression (13.6 vs. 7.0 months; hazard ratio [HR]=0.394; P=0.003) and progression-free survival (11.9 vs. 6.4 months; HR=0.595; P=0.051) were longer with bortezomib-dexamethasone versus bortezomib, respectively. Rates of any-grade adverse events, most common grade 3 or higher adverse events, and discontinuations due to adverse events appeared similar between the groups. Two patients per group died of treatment-related adverse events. These data indicate the potential benefit of bortezomib-dexamethasone compared with single-agent bortezomib at first relapse in myeloma. The MMY-2045, APEX, and DOXIL-MMY-3001 clinical trials were registered at, respectively, clinicaltrials.gov identifier: 00908232, 00048230, and 00103506.
authors.affiliation: Department of Clinical Therapeutics, University of Athens School of Medicine, Greece mdimop@med.uoa.gr.
authors.forename: Meletios A
authors.initials: MA
authors.lastname: Dimopoulos
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Robert Z
authors.initials: RZ
authors.lastname: Orlowski
authors.affiliation: Hôpital Claude-Huriez, Lille, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Facon
authors.affiliation: Department of Hematology, Erasmus Medical Centre, University Hospital Rotterdam, The Netherlands.
authors.forename: Pieter
authors.initials: P
authors.lastname: Sonneveld
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
authors.affiliation: Hematology Department, The Ankara University School of Medicine, Turkey.
authors.forename: Meral
authors.initials: M
authors.lastname: Beksac
authors.affiliation: Centre Régional de Cancérologie Henry Kaplan (CHRU de Tours), and Hôpital Bretonneau, Tours, France.
authors.forename: Lotfi
authors.initials: L
authors.lastname: Benboubker
authors.affiliation: Haematology Department, Western General Hospital, Edinburgh, Scotland, UK.
authors.forename: Huw
authors.initials: H
authors.lastname: Roddie
authors.affiliation: Janssen-Cilag Pharmaceutical SACI, Athens, Greece.
authors.forename: Anna
authors.initials: A
authors.lastname: Potamianou
authors.affiliation: Janssen-Cilag, Issy Les Moulineaux, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Couturier
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ, USA.
authors.forename: Huaibao
authors.initials: H
authors.lastname: Feng
authors.affiliation: Janssen-Cilag UK, High Wycombe, England, UK.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Ataman
authors.affiliation: Janssen Research & Development, Division of Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: Helgi
authors.initials: H
authors.lastname: van de Velde
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Richardson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D011719:Pyrazines / Q000008:administration & dosage; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D003907:Dexamethasone