title: Analysis of renal impairment in MM-003, a phase III study of pomalidomide + low - dose dexamethasone versus high - dose dexamethasone in refractory or relapsed and refractory multiple myeloma.
abstract: Pomalidomide + low-dose dexamethasone is effective and well tolerated for refractory or relapsed and refractory multiple myeloma after bortezomib and lenalidomide failure. The phase III trial MM-003 compared pomalidomide + low-dose dexamethasone with high-dose dexamethasone. This subanalysis grouped patients by baseline creatinine clearance ≥ 30 - < 60 mL/min (n=93, pomalidomide + low-dose dexamethasone; n=56, high-dose dexamethasone) or ≥ 60 mL/min (n=205, pomalidomide + low-dose dexamethasone; n=93, high-dose dexamethasone). Median progression-free survival was similar for both subgroups and favored pomalidomide + low-dose dexamethasone versus high-dose dexamethasone: 4.0 versus 1.9 months in the group with baseline creatinine clearance ≥ 30 - < 60 mL/min (P<0.001) and 4.0 versus 2.0 months in the group with baseline creatinine clearance ≥ 60 mL/min (P<0.001). Median overall survival for pomalidomide + low-dose dexamethasone versus high-dose dexamethasone was 10.4 versus 4.9 months (P=0.030) and 15.5 versus 9.2 months (P=0.133), respectively. Improved renal function, defined as an increase in creatinine clearance from < 60 to ≥ 60 mL/min, was similar in pomalidomide + low-dose dexamethasone and high-dose dexamethasone patients (42% and 47%, respectively). Improvement in progression-free and overall survival in these patients was comparable with that in patients without renal impairment. There was no increase in discontinuations of therapy, dose modifications, and adverse events in patients with moderate renal impairment. Pomalidomide at a starting dose of 4 mg + low-dose dexamethasone is well tolerated in patients with refractory or relapsed and refractory multiple myeloma, and of comparable efficacy if moderate renal impairment is present. This trial was registered with clinicaltrials.gov identifier 01311687 and EudraCT identifier 2010-019820-30.
authors.affiliation: Hematology and Oncology, Department of Medicine, University Hospital Tübingen, Germany katja.weisel@med.uni-tuebingen.de.
authors.forename: Katja C
authors.initials: KC
authors.lastname: Weisel
authors.affiliation: National and Kapodistrian University of Athens, Greece.
authors.forename: Meletios A
authors.initials: MA
authors.lastname: Dimopoulos
authors.affiliation: Hematology, University Hospital Hôtel-Dieu, Nantes, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Martha Q
authors.initials: MQ
authors.lastname: Lacy
authors.affiliation: Vancouver General Hospital, BC, Canada.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Song
authors.affiliation: Department of Hematology, University Hospitals 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: Universitäts Klinikum Heidelberg, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Goldschmidt
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, Hospital Germans Trias I Pujol, Barcelona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Oriol
authors.affiliation: Hospital Universitario La Princesa, Madrid, Spain.
authors.forename: Adrian
authors.initials: A
authors.lastname: Alegre
authors.affiliation: Princess Margaret Hospital, Toronto, ON, Canada.
authors.forename: Christine
authors.initials: C
authors.lastname: Chen
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: Hôpital Saint-Antoine, Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Garderet
authors.affiliation: GUZ Moscow City Clinical Hospital S. P. Botkin, Moscow, Russia.
authors.forename: Valentina
authors.initials: V
authors.lastname: Ivanova
authors.affiliation: Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Martinez-Lopez
authors.affiliation: Hematology and Oncology, Würzburg University Medical Center, Würzburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Knop
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: Clínica Universidad de Navarra, CIMA, IDISNA, Pamplona, Spain.
authors.forename: Jesus
authors.initials: J
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*; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D051437:Renal Insufficiency / Q000175:diagnosis* / Q000209:etiology*; D019233:Retreatment; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome
chemical_list: D013792:Thalidomide; D003907:Dexamethasone; C467566:pomalidomide