Impact of the relative dose intensity on survival of patients with high‐risk myelodysplastic syndromes treated with Azacitidine

Abstract

Abstract We performed a retrospective analysis of 93 myelodysplastic syndromes (MDS) patients with intermediate 2 or high‐risk IPSS score to study the impact of Azacitidine (AZA) relative dose intensity (RDI) <80% on the overall survival (OS). There were 51.6% of patients who had full dose and 48.4% had dose reduction or delayed with a RDI <80%. Nineteen patients (20.4%) had RDI <80% before getting objective response. Overall and progression‐free survivals (OS, PFS) probabilities for the whole population were 58% (95% CI: 48‐69) and 47% (95% CI: 38‐58) at 1 year; 35% (95% CI: 26‐47) and 31% (95% CI: 23‐43) at two years, respectively. When analyzing the outcomes according to the response to AZA, median OS was 32 months (range: 26‐55) for responders and 8 months (range: 7‐12) for nonresponders, with a respective 1‐year and 2‐year OS probabilities of 91% vs 28% and 66% vs 6%, respectively (P < 0.001). Interestingly, there was no impact of dose reduction on OS nor on PFS, however, when analyzing the timing of dose reduction as time‐dependent variable, we found that patients who had dose reduction before achieving the objective response, had significantly lower OS (P = 0.02) and PFS (P = 0.01) compared to patients who had dose reduction after achieving the objective response. In multivariate analysis, acute myeloid leukemia with 21%‐30% blasts in BM and poor and very poor karyotype significantly impacted OS, (HR = 2.09, 95% CI: 1.27‐3.44, P = 0.004, and HR = 2.73, 95% CI: 1.6‐4.6, P < 0.001 respectively), as well as PFS (HR = 1.84, 95% CI: 1.07‐3.17, P = 0.028, and HR = 3.03, 95% CI: 1.7‐5.39, P < 0.001, respectively).

Keywords

• Azacitidine
• dose intensity
• myelodisplastic syndromes