Azacitidine has limited activity in ‘real life’ patients with MDS and AML: a single centre experience

Abstract

Myelodysplastic syndrome (MDS) represents a heterogeneous group of potentially malignant diseases of bone-marrow stem cells. Acute myelogenous leukaemia (AML) is an inevitable outcome for many patients with MDS. Azacitidine has been reported to result in comparably higher response rates and improved survival than other treatment strategies. In this retrospective study, we report the results on 25 'real life' patients with MDS, CMML or AML treated with azacitidine between 2005 and 2009. All patients fulfilled the World Health Organization criteria for MDS and AML. No eligibility criteria other than diagnosis were considered. Complete response (CR) rate was observed in three of the 25 'real life' patients (12%) with a median duration of CR of 5 months (4-6 months). Seven patients (28%) had mono- or bi-lineage haematologic improvement and 15 patients (60%) showed neither morphologic nor haematologic response. Among 17 non-AML patients, the median time from onset of Aza-C treatment to AML transformation was 10 months (4-15 months). Overall death rate was 72%. All of the eight AML patients died. The death rate under Aza-C among non-AML patients was 59%. Unlike the results of the clinical trials, our data show that Aza-C has a limited activity in 'real-life' patients with MDS and AML. It is obvious that Aza-C can induce complete or partial responses in a considerable number of MDS patients but responses are usually not durable as we observed in our patients.

Efficacy of the hypomethylating agents as frontline, salvage, or consolidation therapy in adults with acute myeloid leukemia (AML)

“…In fact the NCCN guidelines now include recommendations for use of hypomethylating agents for elderly or unfit patients. However the utility of this approach in the real world setting has come into doubt with recent reports showing little activity in higher risk patients [16–17]. In the first line setting at our institution the hypomethylating agents showed a response rate of 26.5% (CR+CRi).…”

“…However, reports in real world settings have cast some doubt on their utility [16]. The FDA recently declined to give decitabine approval for an indication in AML because a pivotal phase III trial failed to show a survival benefit except in an unplanned post-hoc analysis [17].…”

Safety and efficacy of azacitidine in Belgian patients with high-risk myelodysplastic syndromes, acute myeloid leukaemia, or chronic myelomonocytic leukaemia: results of a real-life, non-interventional post-marketing survey

“…Previous real-life studies assessed azacitidine efficacy in French [patient-named programme: authorization for temporary utilization (ATU)], Dutch, Turkish, Italian, Scottish or Austrian patients with MDS, AML, or CMML. [28][29][30][31][32][33][34] The Scottish, Italian and Turkish studies also evaluated the azacitidine safety profile. The current survey evaluated safety and efficacy of azacitidine in Belgian MDS, AML, or CMML patients treated in a real-life setting.…”

“…28,29,[31][32][33][34] Among the MDS patients included in this survey, there were more Int-2 (70.6%) and less high-risk patients (20.6%) compared to the French ATU study (54% Int-2 and 43% high-risk), 29 probably due to Responders were defined as patients with complete remission, partial remission, complete remission with incomplete blood count recovery (acute myeloid leukaemia patients) or haematological improvement. Non-responders were defined as patients with treatment failure.…”

Integrated bioinformatic analysis of microarray data reveals shared gene signature between MDS and AML

“…When normal differentiation is hampered, the accumulation of immature HSCs and malignant neoplastic proliferation will occur. Myeloid disorders, especially myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), are the most frequently reported malignant cases, which cause high mortality in adults (3). MDS is defined as clonal HSC malignancies characterized by ineffective hematopoiesis and dysplasia, with clinical manifestations of peripheral cytopenias, hypercellular BM, and variable degrees of increased blasts (4).…”