Azacitidine in untreated acute myeloid leukemia: A report on 149 patients

Abstract

Limited data are available on azacitidine (AZA) treatment and its prognostic factors in acute myeloid leukemia (AML). One hundred and forty‐nine previously untreated AML patients considered ineligible for intensive chemotherapy received AZA in a compassionate patient‐named program. AML diagnosis was de novo, post‐myelodysplastic syndromes (MDS), post‐MPN, and therapy‐related AML in 51, 55, 13, and 30 patients, respectively. Median age was 74 years, median white blood cell count (WBC) was 3.2 × 109/L and 58% of the patients had ≥30% marrow blasts. Cytogenetics was adverse in 60 patients. Patients received AZA for a median of five cycles (range 1–31). Response rate (including complete remission/CR with incomplete recovery/partial remission) was 27.5% after a median of three cycles (initial response), and 33% at any time (best response). Only adverse cytogenetics predicted poorer response. Median overall survival (OS) was 9.4 months. Two‐year OS was 51% in responders and 10% in non‐responders (P<0.0001). Adverse cytogenetics, WBC >15 × 109/L and ECOG‐PS ≥2 predicted poorer OS, while age and marrow blast percentage had no impact. Using MDS IWG 2006 response criteria, among patients with stable disease, those with hematological improvement had no significant survival benefit in a 7 months landmark analysis. Outcomes observed in this high‐risk AML population treated with AZA deserve comparison with those of patients treated intensively in prospective studies. Am. J. Hematol. 89:410–416, 2014. © 2013 Wiley Periodicals, Inc.

Epigenetic targeting and personalized approaches for AML

“…43 In France, 149 newly diagnosed older patients with AML were treated with the same dose and schedule of azacitidine on a compassionate use protocol, with an overall response rate of 33%, CR or CR with incomplete platelet recovery rates of 23%, and an overall survival of 9.4 months. 44 A smaller study of 35 untreated AML patients treated with azacitidine on an Italian compassionate use protocol showed similar results, with 31% CRs and an overall survival of 9 months. 45 As with decitabine, most responding patients in the AML trials received ongoing treatment cycles with azacitidine until progression or toxicity.…”

Comparison of epigenetic versus standard induction chemotherapy for newly diagnosed acute myeloid leukemia patients ≥60 years old

“…HMA inhibit epigenetic silencing of cell-cycle regulatory elements and tumor suppressor genes, thus suppressing the reversible epigenetic changes that play a major role in pathogenesis of leukemogenesis [13][14][15][16]. Two agents, decitabine (Dec) and azacitidine (Aza), have been approved for the treatment of patients with myelodysplastic syndrome (MDS) and have been well tolerated in elderly individuals, leading to multiple clinical trials evaluating their use in older AML patients [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32]. The earliest clinical data of HMAs in AML patients were noncomparative trials mostly involving individuals unfit for IC [17][18][19][20]25].…”

Low Dose Cytosine Arabinoside and Azacitidine Combination in Elderly Patients with Acute Myeloid Leukemia and Refractory Anemia with Excess Blasts (MDS-RAEB2)

“…In a retrospective study conducted by Radujkovic et al, azacitidine and LD-ara-c treatments were compared, and response rates were determined to be 14 and 7 %, respectively [1]. In a multi-center study conducted with 155 AML patients, while the overall response rate was determined to be 52.3 %, the median overall survival as 9.8 months with azacitidine therapy, similarly to ours, these rates were reported as 33 % and 9.4 months in another multi-center study including 149 patients [12,13]. Pleyer et al reported in a large prospective trial that azacitidine can be safely and effectively used in elderly patients.…”

“…Chen et al reported that the pretreatment factors that influence prognosis were found to be a good performance score (Eastern Cooperative Oncology Group PS 0-1), LDH level (higher than 2 fold of normal), hyperleukocytosis (WBC [ 100 000/ll), significant thrombocytopenia (\ 20 000/ll) in 205 AML patients [20]. In a study conducted on 149 AML patients having a poor cytogenetic structure, WBC [ 15 000/ll, the ECOG performance score C2, and the response to therapy were determined to be the factors influencing overall survival [13]. When the side effects were analyzed in both treatment groups, a statistically significant difference was not detected between treatment-related neutropenia, thrombocytopenia, anemia, the amount of blood transfusion, grade of infection, diarrhea, skin reaction, hospitalizationrequiring infection, and duration of hospital stay, and this is consistent with the literature [11,21,22].…”