Azacitidine in patients with WHO-defined AML – Results of 155 patients from the Austrian Azacitidine Registry of the AGMT-Study Group

Abstract

ObjectiveThe Austrian Azacitidine Registry is a multi-center database (ClinicalTrials.gov: NCT01595295). The nature and intent of the registry was to gain a comprehensive view of the use, safety and efficacy of the drug in a broad range of AML-patients treated in real-life scenarios.Patients and methodsThe sole inclusion criteria were the diagnosis of WHO-AML and treatment with at least one dose of azacitidine. No formal exclusion criteria existed. A total of 155 AML-patients who were mostly unfit/ineligible for intensive chemotherapy, or had progressed despite conventional treatment, were included. True ITT-analyses and exploratory analyses regarding the potential prognostic value of baseline-variables/performance-/comorbidity-/risk-scores on overall survival (OS), were performed.ResultsIn this cohort of 155 pretreated (60%), and/or comorbid (87%), elderly (45% ≥75 years) AML-patients, azacitidine was well tolerated and efficacious, with an overall response rate (CR, mCR, PR, HI) of 45% in the total cohort (ITT) and 65% in patients evaluable according to IWG-criteria, respectively. Pre-treatment with conventional chemotherapy (P = .113), age ≤/>80 years (P = .853), number of comorbidities (P = .476), and bone marrow (BM) blast count (P = .663) did not influence OS. In multivariate analysis hematologic improvement alone (without the requirement of concomitant bone marrow blast reduction), although currently not regarded as a standard form of response assessment in AML, was sufficient to confer OS benefit (18.9 vs. 6.0 months; P = .0015). Further deepening of response after first response was associated with improved OS (24.7 vs. 13.7 months; P < .001).ConclusionsIn this large cohort of AML-patients treated with azacitidine, age >80 years, number of comorbidities and/or BM-blasts >30% did not adversely impact OS.

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.…”

“…29,34 The azacitidine safety profile was consistent with previous findings. 20,28,31,33 The most common TEAEs were general disorders, administration site reactions, gastrointestinal disorders, and infections. Treatmentrelated and grade 3-4 TEAEs were also consistent with those reported in the AZA-001 trial.…”

“…. 28,29,33,34 However, the ATU and the Dutch studies included a higher number of high-risk patients, who are more likely to discontinue treatment earlier due to haematological complications or death than Int-2 MDS patients. The majority of Belgian patients received the US Food and Drug Administration-and EMA-approved azacitidine schedule (75 mg/m 2 /day for 7 days every 28 days), and about 25% of patients received shorter schedules, mostly due to AE/death, disease progression, and non-response.…”

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].…”