Use of Azacitidine or Decitabine for the Up-Front Setting in Acute Myeloid Leukaemia: A Systematic Review and Meta-Analysis

Abstract

Irruption of decitabine and azacitidine has led to profound changes in the upfront management of older acute myeloid leukaemia (AML). However, they have not been directly compared in a randomised clinical trial. In addition, there are no studies comparing the optimal treatment schedule of each drug in AML. A systematic review and meta-analysis on the efficacy of decitabine and azacitidine monotherapy in newly diagnosed AML was conducted. Randomised controlled trials and retrospective studies were included. A total of 2743 patients from 23 cohorts were analysed (10 cohorts of azacitidine and 13 of decitabine). Similar response rates were observed for azacitidine (38%, 95% CI: 30–47%) compared to decitabine (40%, 95% CI: 32–48%) (p = 0.825). Overall survival (OS) between azacitidine (10.04 months, 95% CI: 8.36–11.72) and decitabine (8.79 months, 95% CI: 7.62–9.96) was also similar (p = 0.386). Patients treated with azacitidine showed a lower median OS when azacitidine was administered for 5 days (6.28 months, 95% CI: 4.23–8.32) compared to the standard 7-day schedule (10.83 months, 95% CI: 9.07–12.59, p = 0.002). Among patients treated with decitabine, response rates and OS were not significantly different between 5-day and 10-day decitabine regimens. Despite heterogeneity between studies, we found no differences in response rates and OS in AML patients treated with azacitidine or decitabine.

Comparison between azacitidine and decitabine as front-line therapy in elderly treatment naïve Acute Myeloid Leukemia not eligible for intensive chemotherapy

“…Likewise, the better OS of our patients compared with Zeidan's series depends not only on the shortened duration of exposure (in the Zeidan's study the median number of cycles delivered 3 for both HMA, with only 41.8% of patients receiving ≥ 4 cycles), but also on the use of a non-optimal dosage, as only 34.3% of patients treated with AZA followed a 7-day regimen, whereas in our study > 90% of patients followed the classic 7day schedule. A recent meta-analysis con rms our observation and supports the superior effectiveness of the standard dose scheme of AZA over reduced dosages (median OS 10.83 months, 95% CI: 9.07-12.59 vs 6.28 months, 95% CI: 4.23-8.32, respectively p = 0.002) [21]. Our study further reinforces and con rms the ndings of the Zeidan's study.…”

“…In our study, the 30-day and 1-year mortality rate was 6% for both drugs and 50.2% vs 50.7%, respectively. These results are highly comparable to a recent Spanish "real world", study in which 30 days and 1-year mortality for AZA and DEC treated patients were 5.5% vs 3.6% and 58.1% vs 63.6%, respectively [30], and further strengthened in a recent meta-analysis on more than 2000 patients (6% vs 7% and 57% vs 62%, respectively) [21]. In our series, the most frequent cause of 1-year mortality (equally distributed across AZA and DEC cohort) was disease progression (52%) compared to infectious or haemorrhagic complications (24%).…”

Role of Pharmacogenetics in the Treatment of Acute Myeloid Leukemia: Systematic Review and Future Perspectives

“…Hypomethylation can restore the function of tumor suppressor genes in cancer cells. Azacitidine and decitabine are used indistinctly, depending on the preference of the practitioner, as the superiority of either has not yet been demonstrated [ 99 ].…”

A randomised evaluation of low‐dose cytosine arabinoside plus lenalidomide versus single‐agent low‐dose cytosine arabinoside in older patients with acute myeloid leukaemia: Results from the LI‐1 trial

“…Many patients with acute myeloid leukaemia (AML) diagnosed after 60 years of age are not considered suitable for intensive remission‐induction chemotherapy, either due to comorbidities or frailty associated with advanced age 1 . Despite treatment with either low‐dose cytosine arabinoside (LDAC) or a hypomethylating agent, 2,3 survival is usually poor, with 1‐year overall survival (OS) after LDAC of 21%–32% in NCRI AML16 and historical arms of LI‐1 3 . Combination therapy with a backbone of LDAC or a hypomethylating agent with additional agents represents an attractive option, with the potential to improve patient outcomes without substantially increasing toxicity 4–7 …”