title: Low efficacy and high mortality associated with clofarabine treatment of relapsed/refractory acute myeloid leukemia and myelodysplastic syndromes.
abstract: Clofarabine, a second-generation nucleoside analog, has clinical activity in relapsed or refractory acute myelogenous leukemia (AML) and higher-risk myelodysplastic syndromes (MDS). However, there are few data evaluating performance of clofarabine in populations of patients not enrolled in clinical trials. We reviewed outcomes for 84 patients treated with clofarabine for relapsed or refractory AML or MDS, either with clofarabine as monotherapy (n=19) or in combination with cytarabine (n=65). Using International Working Group (IWG) response criteria, the overall response rate (ORR) of all treated patients was 21%, with a complete response rate with either complete or incomplete hematopoietic recovery (CRR=CR+CRi) of 14%. For combination therapy, ORR was 22% with CRR of 18%, and monotherapy patients had an ORR of 21% with CRR of 11%. Although limited by small numbers, subgroup analysis did not reveal variation in response rates when comparing different risk factors. The 30-day mortality was 21% and median survival was 3 months; a subset of 12 patients who were able to go to transplant had an 18-month median survival. Clofarabine's efficacy in a "real-world" setting appears to be less than has been reported in clinical trials, and treatment is associated with a high early mortality rate.
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Roberts
authors.affiliation: Division of Hematological Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Martha
authors.initials: M
authors.lastname: Wadleigh
authors.affiliation: Department of Pharmacy, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Anne M
authors.initials: AM
authors.lastname: McDonnell
authors.affiliation: Division of Hematological Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: DeAngelo
authors.affiliation: Division of Hematological Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Stone
authors.affiliation: Division of Hematological Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: david_steensma@dfci.harvard.edu.
authors.forename: David P
authors.initials: DP
authors.lastname: Steensma
mesh_terms: D000227:Adenine Nucleotides / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D001087:Arabinonucleosides / Q000008:administration & dosage*; D000077866:Clofarabine; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000401:mortality; D012008:Recurrence; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors
chemical_list: D000227:Adenine Nucleotides; D000964:Antimetabolites, Antineoplastic; D001087:Arabinonucleosides; D000077866:Clofarabine
keywords: Acute myeloid leukemia; Clofarabine; Cytarabine; Myelodysplastic syndromes