TY - JOUR
T1 - Clofarabine Plus Low-Dose Cytarabine Is as Effective as and Less Toxic Than Intensive Chemotherapy in Elderly AML Patients
AU - Takahashi, Koichi
AU - Kantarjian, Hagop
AU - Garcia-Manero, Guillermo
AU - Borthakur, Gautam
AU - Kadia, Tapan
AU - Dinardo, Courtney
AU - Jabbour, Elias
AU - Pierce, Sherry
AU - Estrov, Zeev
AU - Konopleva, Marina
AU - Andreeff, Michael
AU - Ravandi, Farhad
AU - Cortes, Jorge
N1 - Funding Information:
This study was supported by the NIH/NCI under award number P30CA016672 .
Publisher Copyright:
© 2016 Elsevier Inc. All rights reserved.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - Introduction Most patients with acute myeloid leukemia (AML) age ≥ 60 years are not offered intensive induction because of high mortality. Phase 2 studies of clofarabine plus low-dose cytarabine (CLDA) as frontline therapy for elderly AML patients demonstrated high response and acceptable toxicity. Patients and Methods We hypothesized that induction therapy with CLDA provides equivalent outcomes to but is less toxic than intensive induction in these patients. To test this hypothesis, we conducted a propensity score-matched comparison of AML patients age ≥ 60 years given induction CLDA versus idarubicin and cytarabine (IA). Ninety-five patients in both groups were matched according to their propensity score. Results We did not observe statistically significant differences in response, overall survival, or mortality rate between the two induction regimens. However, CLDA produced significantly fewer grade 3 or worse toxicities (46% for CLDA vs. 62% for IA; P =.03). Furthermore, among responders, the median response duration was significantly longer with CLDA when we censored patients who underwent stem cell transplantation (15.9 months for CLDA vs. 7.0 months for IA; P =.033). Conclusion Compared with intensive induction, CLDA offers equivalent responses and survival but less toxicity in clinically well-matched cohorts of elderly AML patients. Prospective randomized trials to confirm these findings are warranted.
AB - Introduction Most patients with acute myeloid leukemia (AML) age ≥ 60 years are not offered intensive induction because of high mortality. Phase 2 studies of clofarabine plus low-dose cytarabine (CLDA) as frontline therapy for elderly AML patients demonstrated high response and acceptable toxicity. Patients and Methods We hypothesized that induction therapy with CLDA provides equivalent outcomes to but is less toxic than intensive induction in these patients. To test this hypothesis, we conducted a propensity score-matched comparison of AML patients age ≥ 60 years given induction CLDA versus idarubicin and cytarabine (IA). Ninety-five patients in both groups were matched according to their propensity score. Results We did not observe statistically significant differences in response, overall survival, or mortality rate between the two induction regimens. However, CLDA produced significantly fewer grade 3 or worse toxicities (46% for CLDA vs. 62% for IA; P =.03). Furthermore, among responders, the median response duration was significantly longer with CLDA when we censored patients who underwent stem cell transplantation (15.9 months for CLDA vs. 7.0 months for IA; P =.033). Conclusion Compared with intensive induction, CLDA offers equivalent responses and survival but less toxicity in clinically well-matched cohorts of elderly AML patients. Prospective randomized trials to confirm these findings are warranted.
KW - Acute myeloid leukemia
KW - Clofarabine
KW - Induction therapy
KW - Intensive chemotherapy
KW - Propensity matching
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U2 - 10.1016/j.clml.2015.11.016
DO - 10.1016/j.clml.2015.11.016
M3 - Article
C2 - 26752456
AN - SCOPUS:84958895033
SN - 2152-2650
VL - 16
SP - 163-168.e2
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
IS - 3
ER -