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
Y1 - 2012/9
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
SN - 1083-8791
VL - 18
SP - 1455
EP - 1461
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 9
ER -