A Phase I Dose-Escalation Trial of High-Dose Melphalan with Palifermin for Cytoprotection Followed by Autologous Stem Cell Transplantation for Patients with Multiple Myeloma with Normal Renal Function

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

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13 Scopus citations


Melphalan 200 mg/m2 is the standard conditioning regimen for patients with multiple myeloma (MM) with normal renal function (NRF) undergoing autologous stem cell transplant (ASCT). In an effort to escalate the dose of melphalan and to improve the efficacy, we designed a dose-escalation study of melphalan in conjunction with palifermin in patients with NRF, with the hope that a higher dose of melphalan can be administered with an acceptable degree of oral mucositis (OM). We enrolled 19 patients (18 evaluable) with NRF. Dose-escalation of melphalan administered on day -2 began at 200 mg/m2 with palifermin administered at a fixed dose of 60 mcg/kg/day. Palifermin was given as an i.v. bolus on day -5, -4, and -3, and then on day +1, +2, and +3. Subsequent dose escalations of melphalan were done at 20 mg/m2 increments up to a maximum dose of 280 mg/m2. Of 18 evaluable patients, there were no treatment-related deaths by day 100. The median age was 48.5 years (range, 33-65 years). The most common adverse events related to palifermin included rash (18 events, no ≥grade 3 events), elevation of amylase (10 events, 4 were grade 3 but asymptomatic), and lipase (5 events, 2 were grade 3 but asymptomatic), edema (11 events, no ≥grade 3). The overall incidence of OM grade 3 was 44% (8/18) with a median duration of severe mucositis of 5 days (range, 3-6 days). Eleven patients (61%) required opioid analgesics. None of the patients received total parenteral nutrition (TPN)/nasogastric feeding. Two of 6 patients who were given melphalan 280 mg/m2 did not develop OM. Cardiac dose-limiting toxicity (DLT) in the form of atrial fibrillation did occur in 1 of 6 patients treated with melphalan 280 mg/m2. Palifermin has permitted safe dose escalation of melphalan up to 280 mg/m2, thus reaching the cumulative dosage of melphalan administered in tandem ASCT. This higher dose of melphalan has the potential to improve the efficacy and, hopefully, outcomes of patients with MM with a single ASCT. A phase 2 trial is necessary to better delineate the antimyeloma efficacy of this regimen.

Original languageEnglish (US)
Pages (from-to)56-61
Number of pages6
JournalBiology of Blood and Marrow Transplantation
Issue number1
Publication statusPublished - Jan 1 2013



  • High-dose melphalan
  • Oral mucositis
  • Palifermin

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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