Melphalan 200 mg/m2 in 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.