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

Muneer H. Abidi, Rishi Agarwal, Lois Ayash, Abhinav Deol, Zaid Al-Kadhimi, Judith Abrams, Simon Cronin, Marie Ventimiglia, Lawrence Lum, Jeffrey Zonder, Voravit Ratanatharathorn, Joseph Uberti

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

High-dose melphalan 140 mg/m2 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 m2, 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/m2. 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/m2) developed grade 4 OM, hence reaching DLT. No DLT was observed in 6 patients enrolled in L3 (melphalan 180 mg/m2). Palifermin has permitted safe dose escalation of melphalan up to 180 mg/m2 in patients with RI.

Original languageEnglish (US)
Pages (from-to)1455-1461
Number of pages7
JournalBiology of Blood and Marrow Transplantation
Volume18
Issue number9
DOIs
StatePublished - Sep 2012
Externally publishedYes

Keywords

  • Autologous stem cell transplant
  • High-dose melphalan
  • Myeloma
  • Palifermin

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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