Epigenetic therapy is associated with similar survival compared with intensive chemotherapy in older patients with newly diagnosed acute myeloid leukemia.
We reviewed the outcome of 671 patients 65 years of age or older with newly diagnosed acute myeloid leukemia (AML) treated at our institution between 2000 and 2010 with intensive chemotherapy (n = 557) or azacitidine- or decitabine-based therapy (n = 114). Both groups were balanced according to cytogenetics and performance status. The complete response rates with chemotherapy and epigenetic therapy were 42% and 28%, respectively (P = .001), and the 8-week mortality 18% and 11%, respectively (P = .075). Two-year relapse-free survival rates (28% vs 39%, P = .843) and median survival (6.7 vs 6.5 months, P = .413) were similar in the 2 groups. Multivariate analysis identified older age, adverse cytogenetics, poor performance status, elevated creatinine, peripheral blood and BM blasts, and hemoglobin, but not type of AML therapy, as independent prognostic factors for survival. No outcome differences were observed according to cytogenetics, FLT3 mutational status, age, or performance status by therapy type. Decitabine was associated with improved median overall survival compared with azacitidine (5.5 vs 8.8 months, respectively, P = .03). Survival after failure of intensive chemotherapy, azacitidine, or decitabine was more favorable in patients who had previously received decitabine (1.1 vs 0.9 vs 3.1 months, respectively, P = .109). The results of the present study show that epigenetic therapy is associated with similar survival rates as intensive chemotherapy in older patients with newly diagnosed AML. The studies reviewed are registered at www.clinicaltrials.gov as 2009-0172 (NCT00926731) and 2009-0217 (NCT00952588).
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4095, USA. aquintas@mdanderson.org
Alfonso
A
Quintás-Cardama
Farhad
F
Ravandi
Theresa
T
Liu-Dumlao
Mark
M
Brandt
Stefan
S
Faderl
Sherry
S
Pierce
Gautam
G
Borthakur
Guillermo
G
Garcia-Manero
Jorge
J
Cortes
Hagop
H
Kantarjian
D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D019175:DNA Methylation / Q000187:drug effects; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D000077209:Decitabine; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D015999:Multivariate Analysis; D009154:Mutation; D011379:Prognosis; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
D004791:Enzyme Inhibitors; D000077209:Decitabine; D015254:DNA Modification Methylases; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3; D001374:Azacitidine