title: Cytogenetics and long-term survival of patients with refractory or relapsed and refractory multiple myeloma treated with pomalidomide and low-dose dexamethasone.
abstract: Patients with refractory or relapsed and refractory multiple myeloma who no longer receive benefit from novel agents have limited treatment options and short expected survival. del(17p) and t(4;14) are correlated with shortened survival. The phase 3 MM-003 trial demonstrated significant progression-free and overall survival benefits from treatment with pomalidomide plus low-dose dexamethasone compared to high-dose dexamethasone among patients in whom bortezomib and lenalidomide treatment had failed. At an updated median follow-up of 15.4 months, the progression-free survival was 4.0 versus 1.9 months (HR, 0.50; P<0.001), and median overall survival was 13.1 versus 8.1 months (HR, 0.72; P=0.009). Pomalidomide plus low-dose dexamethasone, compared with high-dose dexamethasone, improved progression-free survival in patients with del(17p) (4.6 versus 1.1 months; HR, 0.34; P <0.001), t(4;14) (2.8 versus 1.9 months; HR, 0.49; P=0.028), and in standard-risk patients (4.2 versus 2.3 months; HR, 0.55; P<0.001). Although the majority of patients treated with high-dose dexamethasone took pomalidomide after discontinuation, the overall survival of patients treated with pomalidomide plus low-dose dexamethasone or high-dose dexamethasone was 12.6 versus 7.7 months (HR, 0.45; P=0.008) in patients with del(17p), 7.5 versus 4.9 months (HR, 1.12; P=0.761) in those with t(4;14), and 14.0 versus 9.0 months (HR, 0.85; P=0.380) in standard-risk subjects. The overall response rate was higher in patients treated with pomalidomide plus low-dose dexamethasone than in those treated with high-dose dexamethasone both among standard-risk patients (35.2% versus 9.7%) and those with del(17p) (31.8% versus 4.3%), whereas it was similar in patients with t(4;14) (15.9% versus 13.3%). The safety of pomalidomide plus low-dose dexamethasone was consistent with initial reports. In conclusion, pomalidomide plus low-dose dexamethasone is efficacious in patients with relapsed/refractory multiple myeloma and del(17p) and/or t(4;14). This study is registered at ClinicalTrials.gov as NCT01311687 and with EudraCT as 2010-019820-30.
authors.affiliation: Alexandra Hospital, Athens, Greece mdimop@med.uoa.gr.
authors.forename: Meletios A
authors.initials: MA
authors.lastname: Dimopoulos
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 Catala d'Oncologia, HGTiP, Barcelona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Oriol
authors.affiliation: Hopital Saint Antoine, Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Garderet
authors.affiliation: Seràgnoli Institute of Hematology, Bologna University School of Medicine, 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: Alfred Hospital-Monash University, Melbourne, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Spencer
authors.affiliation: University of Würzburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Knop
authors.affiliation: University of Calgary, AB, Canada.
authors.forename: Nizar J
authors.initials: NJ
authors.lastname: Bahlis
authors.affiliation: University Hospital Zurich, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Renner
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: Kevin
authors.initials: K
authors.lastname: Hong
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: Clinica Universidad de Navarra, CIMA, Pamplona, Spain.
authors.forename: Jesus F
authors.initials: JF
authors.lastname: San Miguel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002869:Chromosome Aberrations; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D012008:Recurrence; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome
chemical_list: D013792:Thalidomide; D003907:Dexamethasone; C467566:pomalidomide