Real-Life Efficacy Of Azacitidine In Myelodysplastic Syndromes According To IPSS Cytogenetic Profile

In the AZA001 trial, azacitidine prolonged OS in all cytogenetic IPSS risk subgroups and in particular reduced 67% risk of death for all patients with -7/del(7q). Aim of our study was to assess azacitidine efficacy according to cytogenetic risk at baseline in a large group of intermediate/high-risk MDS patients treated outside clinical trials. One hundred and sixty-six patients represented the whole cohort of patients with primary or secondary MDS (CMML were excluded) diagnosed and treated with azacitidine in 6 different hematologic units. Patients were recruited consecutively, without any criteria of exclusion. All patients received azacitidine with a schedule of 5+2+2 or of 7 consecutive days every 28 days until progression or unacceptable toxicity. Clinical parameters (age, sex, WHO classification, IPSS) and baseline cytogenetic evaluation were retrospectively collected. Of 166 patients recruited, 103 were males and 63 females; median age was 69.5 years (range 49-89). A median of 8 cycles was performed (range 1-60). According to IPSS stratification there were 29 patients with intermediate-1 risk, 118 patients with intermediate-2 and 15 high–risk (7 patients not determined). According to WHO classification, 37 patients were diagnosed as having RAEB-1, 101 patients as RAEB-2, 28 patients as RCMD. According to IPSS cytogenetic risk stratification, 88 patients were in the good risk, 22 patients were in intermediate risk and 39 in the poor risk. The most frequent cytogenetic aberration, apart from normal karyotype, was -7 or del(7q). According to cytogenetic stratification, after a median of 4 cycles for the first evaluation, we revealed the following responses according to IWG criteria: of 88 patients classified as good risk, 68 were evaluable and overall 30% achieved a complete (CR), partial remission (PR) or hematological improvement (HI), 59% maintained a stable disease, 4% progressed to acute leukemia and 7% failed to achieve any response. Of 22 patients classified as intermediate cytogenetic risk, 19 patients were evaluable after 4 cycles: overall, 52.6% achieved a CR/PR and 42% maintained a stable disease, none experienced a progression and 5% failed to achieve any response. Of 39 patients stratified as high cytogenetic risk, 30 were evaluable: 36.6% achieved a CR/PR/HI, 36% maintained a stable disease, 20% progressed to acute leukemia and 7% failed to achieve any response. Our results, based on a retrospective evaluation in a large series of patients treated outside clinical trials, shown that azacitidine was clinically effective independently from cytogenetic profile, as proved in the AZA001 trial.