Azacitidine improves survival in patients with myelodysplastic syndromes and acute myeloid leukemia with myelodysplasia-related changes with 20-30% bone marrow blasts and poor-risk cytogenetic categor

Background: Karyotype is a key prognostic factor in MDS and AML. Azacitidine (AZA) has shown survival advantage in high-risk MDS and AML (20%>30% blasts) in a randomized phase III trial. However, data on outcome of MDS and AML (20-30% blasts) with adverse karyotype treated with AZA and compared with conventional regimens are scarce. Aims: To evaluate the role of AZA in MDS and AML with myelodysplasia-related changes (20-30% blasts) with poor-risk cytogenetic categories in an unselect cohort of patients (pts) treated with AZA or conventional care regimens. Methods: Forty pts were retrospectively analyzed (MDS, n=32. AML, n=8). Karyotype was reported according to ISCN. Analysis included pts diagnosed from 2000 to 2013 and those with cytogenetic categories of poor (IPSS) or poor/very poor (IPSS-R). Patients were divided into two groups: Those who received AZA (AZA group, from 2009 to present; n=23, including: RCMD=5, RAEB-2=13, AML=5) and those who did not (non-AZA group, ECOG≤2,prior to AZA approval, from 2000 to 2009; n=17. RCMD=6, RAEB-1=4, RAEB-2=4, CMML=2, AML=3).Non-AZA group included intensive chemotherapy and nonintensive approaches (low-dose ARA-C). Response to therapy was defined by IWG MDS 2006 criteria. Results: There were no differences between both groups in terms of WHO subtype, age, bone marrow (BM) blast% and distribution of pts with chromosome 3 abnormality (abn) or having ≥3 chromosomal abn and pts with monosomal karyotype (MK) versus any other adverse category, although a trend to higher BM blast% and chromosome 3 abn/≥3 abn was noticed in the AZA group as compared to non-AZA cohort (14% vs 6% and 73% vs 53%, respectively). At last follow-up, 10/40 (25%) patients are alive. Median OS was 14 months for AZA pts vs 6 months for non-AZA (P=0.07). Median OS for responding patients to AZA was 20 months (12.9-27). Overall response rate (CR/marrow CR/PR) was 56% (CR=47%, mCR=8%) in the AZA group. Interestingly, 41% of pts with chromosome 3 abn/≥3 chromosomal abn and 45% of pts with MK achieved CR with AZA, with median OS for responders of 16 and 14 months in each category, respectively. Four pts from each cohort underwent SCT. In the multivariable Cox proportional hazard model including SCT as a time-dependent covariate (Table 1), only treatment with AZA significantly influenced on survival (HR 0.33, 95% CI 0.146-0.973;P=0.04). A trend towards a better outcome was also observed in patients treated with IC (P=0.08). Receiving SCT (time-dependent covariate) did not have impact on survival (P=0.15). Severe thrombocytopenia (<50x10e9/L) was associated with a poor outcome (P=0.055; HR=0.860, 95% IC: 0.007-1.059). Summary and Conclusions: These data suggests a potential benefit on overall survival for azacitidine in pts with MDS and AML with myelodysplasiarelated changes and adverse karyotype. Severity of karyotypic abnormalities did not preclude the possibility of achieving response to AZA. Tolerability and no need for hospital admission may favor the clinical decision whether to offer this approach to pts aged >65 years with MDS or AML (20-30% blasts) with adverse cytogenetics. (Table Presented).