Azacitidine in patients with acute myeloid leukemia medically unfit for or resistant to chemotherapy: a multicenter phase I/II study

Abstract

The safety and efficacy of azacitidine (5-day schedule) were assessed in a multicenter study in 40 patients (median age 72 years) with acute myeloid leukemia (AML) medically unfit for (n = 20) or resistant to chemotherapy (n = 20) from April to October 2008. Median marrow blasts were 42%. After a median follow-up of 13 months, response (complete remission [CR]/partial remission [PR]/hematologic improvement [HI]) was 50% and 10% in newly diagnosed and relapsed/refractory patients, respectively (p = 0.008). Median time-to-response was 2.5 months with a median duration of 5.9 months. Median survival was not reached for responders versus 3.8 months for 15 (38%) patients with stable disease (p < 0.045). High-risk cytogenetics was associated with inferior survival (p = 0.05). Lower marrow blasts on day 15 of cycle 1, irrespective of pretreatment count, predicted subsequent response (p = 0.01). Azacitidine is active and well tolerated in elderly patients with newly diagnosed AML.

200 Clinical Outcomes of Aml Patients Treated With Azacitidine in Portugal: A Retrospective Multicenter Study

“…The response rates and the overall survival observed in our study are in consonance to those reported by other groups [16,17,19,26]. It is noteworthy that the rates of CR obtained with AZA are equivalent to those obtained in some published series of elderly patients treated with IC [11].…”

“…In this setting it had proven to be well tolerated including by those more elderly [25]. Based on this experience, several groups have tested the efficacy and safety of AZA in elderly patients with AML with promising results [16,17,19,26].…”

Azacitidine in the treatment of older patients affected by acute myeloid leukemia: A report by the Rete Ematologica Pugliese (REP)

“…Nevertheless, there are conflicting results as to whether, in this patients setting, the achievement of CR can actually have an impact on crude survival [13,14]. A superior OS has been demonstrated in AML patients with 20-30% bone marrow blasts treated with azacitidine compared to conventional treatment [13,14], while three recent studies [16,[29][30] showed a beneficial outcome in previously untreated AML patients, including patients with more than 30% bone marrow blasts, but a correlation with CR and survival remains unclear [13][14][15][16]. In our study, in accordance with the literature [16,22], the response rate seems to be correlated with PS (<2 vs ≥2) and karyotype (adverse vs intermediate) both in univariate and multivariate models (Tables 4 and 5), although the impact of the same variables on OS was confirmed at multivariate analysis only for ECOG ( Table 6).…”

Progress in Acute Myeloid Leukemia

“…Studies of 5-AZA in AML have shown CR rates in the range of 15% - 20% and median OS ranges of 19 to 24.5 months among patients with 20-30% bone marrow blasts and less proliferative disease. 89-94 Decitabine treatment in AML has also produced similar response rates ranging from 18% to 24% and a survival benefit in responding patients (7.7 to 14.4 months). 95,96 A randomized phase III study of decitabine vs. supportive care or LDAC demonstrated a significant OS benefit (7.7 vs. 5 months, p=0.37) and led to its approval by the European Medicines Agency for the treatment of AML in patients ≥ 65 years.…”