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

6 Citations (Scopus)

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 1 2012

Fingerprint

Fibroblast Growth Factor 7
Melphalan
Cytoprotection
Stem Cell Transplantation
Multiple Myeloma
Creatinine
Stomatitis
Renal Insufficiency
Maximum Tolerated Dose
Standard of Care
Atrial Fibrillation
Dialysis

Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

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

In: Biology of Blood and Marrow Transplantation, Vol. 18, No. 9, 01.09.2012, p. 1455-1461.

Research output: Contribution to journalArticle

Abidi, Muneer H. ; Agarwal, Rishi ; Ayash, Lois ; Deol, Abhinav ; Al-Kadhimi, Zaid ; Abrams, Judith ; Cronin, Simon ; Ventimiglia, Marie ; Lum, Lawrence ; Zonder, Jeffrey ; Ratanatharathorn, Voravit ; Uberti, Joseph. / 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. In: Biology of Blood and Marrow Transplantation. 2012 ; Vol. 18, No. 9. pp. 1455-1461.
@article{e5e474bee20e4dfaa0e967e6de5fdcc2,
title = "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",
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.",
keywords = "Autologous stem cell transplant, High-dose melphalan, Myeloma, Palifermin",
author = "Abidi, {Muneer H.} and Rishi Agarwal and Lois Ayash and Abhinav Deol and Zaid Al-Kadhimi and Judith Abrams and Simon Cronin and Marie Ventimiglia and Lawrence Lum and Jeffrey Zonder and Voravit Ratanatharathorn and Joseph Uberti",
year = "2012",
month = "9",
day = "1",
doi = "10.1016/j.bbmt.2012.03.010",
language = "English (US)",
volume = "18",
pages = "1455--1461",
journal = "Biology of Blood and Marrow Transplantation",
issn = "1083-8791",
publisher = "Elsevier Inc.",
number = "9",

}

TY - JOUR

T1 - 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

T2 - Results of a Phase I Trial

AU - Abidi, Muneer H.

AU - Agarwal, Rishi

AU - Ayash, Lois

AU - Deol, Abhinav

AU - Al-Kadhimi, Zaid

AU - Abrams, Judith

AU - Cronin, Simon

AU - Ventimiglia, Marie

AU - Lum, Lawrence

AU - Zonder, Jeffrey

AU - Ratanatharathorn, Voravit

AU - Uberti, Joseph

PY - 2012/9/1

Y1 - 2012/9/1

N2 - 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.

AB - 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.

KW - Autologous stem cell transplant

KW - High-dose melphalan

KW - Myeloma

KW - Palifermin

UR - http://www.scopus.com/inward/record.url?scp=84865163334&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84865163334&partnerID=8YFLogxK

U2 - 10.1016/j.bbmt.2012.03.010

DO - 10.1016/j.bbmt.2012.03.010

M3 - Article

C2 - 22453252

AN - SCOPUS:84865163334

VL - 18

SP - 1455

EP - 1461

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

SN - 1083-8791

IS - 9

ER -