Melphalan 180 mg/m2 Can Be Safely Administered As Conditioning Regimen before an Autologous Stem Cell Transplantation (ASCT) in Multiple Myeloma Patients with Creatinine Clearance 60 mL/min/1.73 m2 or Lower with Use of Palifermin for Cytoprotection: Results of a Phase I Trial

High-dose melphalan 140 mg/m(2) is the standard of care for patients with multiple myeloma (MM) with renal insufficiency (RI). Palifermin as a cytoprotective agent has demonstrated efficacy in reducing the intensity and duration of oral mucositis (OM) in patients who receive intensive chemotherapy/radiotherapy. There is no prospective data on the use of palifermin in patients with MM with RI. Eligibility criteria: creatinine clearance <= 60 mL/minute/ 1.73 m(2), age >18 years, no dialysis, no active OM, and a suitable candidate for autologous stem cell transplant (ASCT). Melphalan dose ranged from 140 to 200 mg/m2 and escalated at the increment of 20 mg/m(2). Six dosages of palifermin 60 mcg/kg/day were given intravenously between day 5 to day +3. Dose escalations were to stop if dose-limiting toxicities (DLTs) occurred at melphalan dose in <= 2 of 3 patients, with that dose declared as the maximal administered dose and the level below where <= 1 of 6 patients had DLTs was considered the maximally tolerated dose (MTD). Nineteen patients were enrolled from June 2007 to June 2011. Data on 15 evaluable patients is reported as 4 patients were removed. Median age was 59 years (range, 36-67 years). The overall incidence of OM >= grade 3 was 53% (8 of 15) and a median duration of grade 3 OM was 6.5 days (range, 3-42 days). One patient in L2 (melphalan 160 mg/m2) developed atrial fibrillation on day +9. Two patients in L4 (melphalan 200 mg/m(2)) developed grade 4 OM, hence reaching DLT. No DLT was observed in 6 patients enrolled in L3 (melphalan 180 mg/m(2)). Palifermin has permitted safe dose escalation of melphalan up to 180 mg/m(2) in patients with RI. Biol Blood Marrow Transplant 18: 1455-1461 (2012) (C) 2012 American Society for Blood and Marrow Transplantation