title: The use of novel drugs can effectively improve response, delay relapse and enhance overall survival in multiple myeloma patients with renal impairment.
abstract: BACKGROUND
  Renal impairment is a common feature in multiple myeloma and is considered a poor prognostic factor.
  
  
  OBJECTIVE
  To determine the impact of novel drugs (i.e. bortezomib, lenalidomide and thalidomide) in the treatment of myeloma patients with renal impairment. The primary endpoint was overall survival and secondary endpoints were time to next treatment and response.
  
  
  METHODS
  The study population included all patients diagnosed with treatment-demanding multiple myeloma January 2000 to June 2011 at 15 Swedish hospitals. Renal impairment was defined as an estimated glomerular filtration rate under 60 mL/min/1.73 m2.
  
  
  RESULTS
  The study population consisted of 1538 patients, of which 680 had renal impairment at diagnosis. The median overall survival in patients with renal impairment was 33 months, which was significantly shorter than 52 months in patients with normal renal function (P<0.001). Novel agents in first line improved overall survival (median 60 months) in non-high-dose treated patients with renal impairment (n = 143) as compared to those treated with conventional cytotoxic drugs (n = 411) (median 27 months) (P<0.001). In the multivariate analysis up front treatment with bortezomib was an independent factor for better overall survival in non-high-dose treated renally impaired patients. High-dose treated renally impaired patients had significantly better median overall survival than non-high-dose ones (74 versus 26 months) and novel drugs did not significantly improve survival further in these patients. Patients with renal impairment had both a shorter median time to next treatment and a lower response rate than those with normal renal function. However, novel drugs and high dose treatment lead to a significantly longer time to next treatment and the use of novel agents significantly improved the response rate of these patients.
  
  
  CONCLUSIONS
  High dose treatment and novel drugs, especially bortezomib, can effectively overcome the negative impact of renal impairment in patients with multiple myeloma.
authors.affiliation: Department of Medicine, Karolinska Institutet Huddinge, Stockholm, Sweden; Hematology Center, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Katarina
authors.initials: K
authors.lastname: Uttervall
authors.affiliation: Department of Medicine, Karolinska Institutet Huddinge, Stockholm, Sweden.
authors.forename: Adil D
authors.initials: AD
authors.lastname: Duru
authors.affiliation: Department of Medicine, Karolinska Institutet Huddinge, Stockholm, Sweden; Hematology Center, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Lund
authors.affiliation: Department of Medicine, Karolinska Institutet Huddinge, Stockholm, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Liwing
authors.affiliation: Department of Medicine, Karolinska Institutet Huddinge, Stockholm, Sweden.
authors.forename: Gösta
authors.initials: G
authors.lastname: Gahrton
authors.affiliation: Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Holmberg
authors.affiliation: Janssen-Cilag AB, Sollentuna, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Aschan
authors.affiliation: Department of Medicine, Karolinska Institutet Huddinge, Stockholm, Sweden; Hematology Center, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Evren
authors.initials: E
authors.lastname: Alici
authors.affiliation: Department of Medicine, Karolinska Institutet Huddinge, Stockholm, Sweden; Hematology Center, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Hareth
authors.initials: H
authors.lastname: Nahi
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D009026:Mortality; D009101:Multiple Myeloma / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology* / Q000401:mortality; D009364:Neoplasm Recurrence, Local; D012042:Registries; D051437:Renal Insufficiency / Q000209:etiology* / Q000503:physiopathology; D019233:Retreatment; D013548:Sweden / Q000453:epidemiology; D016896:Treatment Outcome