title: Impact of prior treatment and depth of response on survival in MM-003, a randomized phase 3 study comparing pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone in relapsed/refractory multiple myeloma.
abstract: Pomalidomide is a distinct oral IMiD(®) immunomodulatory agent with direct antimyeloma, stromal-support inhibitory, and immunomodulatory effects. The pivotal, multicenter, open-label, randomized phase 3 trial MM-003 compared pomalidomide + low-dose dexamethasone vs high-dose dexamethasone in 455 patients with refractory or relapsed and refractory multiple myeloma after failure of bortezomib and lenalidomide treatment. Initial results demonstrated significantly longer progression-free survival and overall survival with an acceptable tolerability profile for pomalidomide + low-dose dexamethasone vs high-dose dexamethasone. This secondary analysis describes patient outcomes by treatment history and depth of response. Pomalidomide + low-dose dexamethasone significantly prolonged progression-free survival and favored overall survival vs high-dose dexamethasone for all subgroups analyzed, regardless of prior treatments or refractory status. Both univariate and multivariate analyses showed that no variable relating to either the number (≤ or > 3) or type of prior treatment was a significant predictor of progression-free survival or overall survival. No cross-resistance with prior lenalidomide or thalidomide treatment was observed. Patients achieving a minimal response or better to pomalidomide + low-dose dexamethasone treatment experienced a survival benefit, which was even higher in those achieving at least a partial response (17.2 and 19.9 months, respectively, as compared with 7.5 months for patients with less than minimal response). These data suggest that pomalidomide + low-dose dexamethasone should be considered a standard of care in patients with refractory or relapsed and refractory multiple myeloma regardless of prior treatment. ClinicalTrials.gov: NCT01311687; EudraCT: 2010-019820-30.
authors.affiliation: Clinica Universidad de Navarra, CIMA, Pamplona, Spain sanmiguel@unav.es.
authors.forename: Jesus F
authors.initials: JF
authors.lastname: San Miguel
authors.affiliation: Hematology & Oncology, Department of Medicine, University Hospital Tübingen, Germany.
authors.forename: Katja C
authors.initials: KC
authors.lastname: Weisel
authors.affiliation: Vancouver General Hospital, Vancouver, BC, Canada.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Song
authors.affiliation: Department of Hematology, University Hospital Leuven, Belgium.
authors.forename: Michel
authors.initials: M
authors.lastname: Delforge
authors.affiliation: Centre Hospitalier Lyon Sud/Hospices Civils de Lyon, Pierre-Bénite, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Karlin
authors.affiliation: University Hospital Heidelberg and German Cancer Research Center, Heidelberg, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Goldschmidt
authors.affiliation: Hematology, University Hospital Hôtel-Dieu, Nantes, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.affiliation: Hematology, Centre Hospitalier de la Côte Basque, Bayonne, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Banos
authors.affiliation: Institut Català d'Oncologia, HGTiP, Barcelona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Oriol
authors.affiliation: Hôpital Saint Antoine, Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Garderet
authors.affiliation: Bologna University School of Medicine, Institute of Hematology and Medical Oncology, Bologna, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Cavo
authors.affiliation: GUZ Moscow City Clinical Hospital S.P. Botkin, Russia.
authors.forename: Valentina
authors.initials: V
authors.lastname: Ivanova
authors.affiliation: Hospital Universitario La Princesa, Madrid, Spain.
authors.forename: Adrian
authors.initials: A
authors.lastname: Alegre
authors.affiliation: Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Martinez-Lopez
authors.affiliation: Princess Margaret Hospital, Toronto, ON, Canada.
authors.forename: Christine
authors.initials: C
authors.lastname: Chen
authors.affiliation: University Hospital Zurich, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Renner
authors.affiliation: University of Calgary, Alberta, Canada.
authors.forename: Nizar Jacques
authors.initials: NJ
authors.lastname: Bahlis
authors.affiliation: Celgene Corporation, Summit, NJ, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Yu
authors.affiliation: Celgene Corporation, Summit, NJ, USA.
authors.forename: Terri
authors.initials: T
authors.lastname: Teasdale
authors.affiliation: Celgene Corporation, Summit, NJ, USA.
authors.forename: Lars
authors.initials: L
authors.lastname: Sternas
authors.affiliation: Celgene Corporation, Summit, NJ, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Jacques
authors.affiliation: Celgene Corporation, Summit, NJ, USA.
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Zaki
authors.affiliation: Alexandra Hospital, Athens, Greece.
authors.forename: Meletios A
authors.initials: MA
authors.lastname: Dimopoulos
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D012008:Recurrence; D019233:Retreatment; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome
chemical_list: D013792:Thalidomide; D003907:Dexamethasone; C467566:pomalidomide