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 S Al-Kadhimi, Judith Abrams, Simon Cronin, Marie Ventimiglia, Lawrence Lum, Voravit Ratanatharathorn, Jeffrey Zonder, Joseph Uberti

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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
Volume19
Issue number1
DOIs
StatePublished - Jan 1 2013

Fingerprint

Fibroblast Growth Factor 7
Melphalan
Cytoprotection
Stem Cell Transplantation
Multiple Myeloma
Kidney
Stomatitis
Stem Cells
Transplants
Mucositis
Total Parenteral Nutrition
Amylases
Exanthema
Lipase
Atrial Fibrillation
Opioid Analgesics
Edema

Keywords

  • High-dose melphalan
  • Oral mucositis
  • Palifermin

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

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

In: Biology of Blood and Marrow Transplantation, Vol. 19, No. 1, 01.01.2013, p. 56-61.

Research output: Contribution to journalArticle

Abidi, Muneer H. ; Agarwal, Rishi ; Tageja, Nishant ; Ayash, Lois ; Deol, Abhinav ; Al-Kadhimi, Zaid S ; Abrams, Judith ; Cronin, Simon ; Ventimiglia, Marie ; Lum, Lawrence ; Ratanatharathorn, Voravit ; Zonder, Jeffrey ; Uberti, Joseph. / 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. In: Biology of Blood and Marrow Transplantation. 2013 ; Vol. 19, No. 1. pp. 56-61.
@article{cdad69a747b9415f981b9c11c26ed8f1,
title = "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",
abstract = "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.",
keywords = "High-dose melphalan, Oral mucositis, Palifermin",
author = "Abidi, {Muneer H.} and Rishi Agarwal and Nishant Tageja and Lois Ayash and Abhinav Deol and Al-Kadhimi, {Zaid S} and Judith Abrams and Simon Cronin and Marie Ventimiglia and Lawrence Lum and Voravit Ratanatharathorn and Jeffrey Zonder and Joseph Uberti",
year = "2013",
month = "1",
day = "1",
doi = "10.1016/j.bbmt.2012.08.003",
language = "English (US)",
volume = "19",
pages = "56--61",
journal = "Biology of Blood and Marrow Transplantation",
issn = "1083-8791",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - 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

AU - Abidi, Muneer H.

AU - Agarwal, Rishi

AU - Tageja, Nishant

AU - Ayash, Lois

AU - Deol, Abhinav

AU - Al-Kadhimi, Zaid S

AU - Abrams, Judith

AU - Cronin, Simon

AU - Ventimiglia, Marie

AU - Lum, Lawrence

AU - Ratanatharathorn, Voravit

AU - Zonder, Jeffrey

AU - Uberti, Joseph

PY - 2013/1/1

Y1 - 2013/1/1

N2 - 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.

AB - 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.

KW - High-dose melphalan

KW - Oral mucositis

KW - Palifermin

UR - http://www.scopus.com/inward/record.url?scp=84871923086&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84871923086&partnerID=8YFLogxK

U2 - 10.1016/j.bbmt.2012.08.003

DO - 10.1016/j.bbmt.2012.08.003

M3 - Article

VL - 19

SP - 56

EP - 61

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

SN - 1083-8791

IS - 1

ER -