title: Melphalan 200 mg/m2in patients with renal impairment is associated with increased short-term toxicity but improved response and longer treatment-free survival.
abstract: Data on the effectiveness and toxicity of high-dose melphalan in patients with renal impairment (RI) are lacking. We evaluated the impact of RI on outcomes of patients with multiple myeloma treated with melphalan 200 mg/m2(Mel200) and autologous stem cell transplantation. Similar baseline characteristics were seen among 46 patients with creatinine clearance (CrCl) <60 mL/min (median 50 mL/min, range 20-59) and 103 patients with CrCl ⩾60 mL/min (median 83 mL/min, range 60-128). Patients with CrCl <60 mL/min had longer time to neutrophil (P=0.008) and platelet engraftment (P<0.001). Diarrhea, duration of total parenteral nutrition use and infection were significantly higher in the CrCl <60 mL/min group. With a median follow-up of 35 months (range 2-132) in the CrCl <60 mL/min group and 47 months (range 1-45) in the CrCl ⩾60 mL/min group, overall survival was comparable between the two groups. Median treatment-free survival was longer in the RI group (37 vs 17 months, P=0.0025). Multivariate analysis showed CrCl <60 mL/min (hazard ratio (HR) 3.5), and prior proteasome inhibitor therapy (HR 2.441) both predicted longer treatment-free survival. We consider Mel200 safe and effective in patients with CrCl between 30 and 60 mL/min.
authors.affiliation: Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, IL, USA.|Cancer Center, University of Illinois, Chicago, IL, USA.
authors.forename: K
authors.initials: K
authors.lastname: Sweiss
authors.affiliation: Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: S
authors.initials: S
authors.lastname: Patel
authors.affiliation: Department of Pharmacy, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: K
authors.initials: K
authors.lastname: Culos
authors.affiliation: Division of Hematology/Oncology, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: A
authors.initials: A
authors.lastname: Oh
authors.affiliation: Cancer Center, University of Illinois, Chicago, IL, USA.|Division of Hematology/Oncology, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: D
authors.initials: D
authors.lastname: Rondelli
authors.affiliation: Cancer Center, University of Illinois, Chicago, IL, USA.|Division of Hematology/Oncology, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: P
authors.initials: P
authors.lastname: Patel
mesh_terms: D000328:Adult; D000368:Aged; D003404:Creatinine / Q000493:pharmacokinetics; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage* / Q000633:toxicity; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000401:mortality / Q000628:therapy*; D051437:Renal Insufficiency / Q000150:complications* / Q000401:mortality; D016019:Survival Analysis
chemical_list: D003404:Creatinine; D008558:Melphalan