Prognostic Factors Associated To Achievement Of Complete Or Partial Response In MDS Patients Treated With Azacitidine Outside Clinical Trials

Azacitidine is able to induce responses and to prolong survival (OS) in intermediate/high risk MDS subgroups or in CMML: in the AZA001 trial, median OS was significantly longer for azacitidine patients compared with the combined conventional care regimen (CCR) group. We retrospectively assessed prognostic factors associated to the achievement of these responses in a large series of MDS patients treated outside clinical trials. Overall, we recruited for this study, 166 primary or secondary MDS and 21 CMML 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 MDS 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 intermediate-1 risk patients, 118 intermediate-2 patients and 15 high–risk patients (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. Of 21 CMML patients recruited, 19 were males and 2 females; median age was 67.5 years (range 62-89). According to WHO classification, 14 patients were CMML-2. Overall, 41 patients (22%) achieved a CR/PR according to IWG 2009 criteria. Analysis of factors associated to the achievement of best responses revealed that pre-azacitidine WBC higher than 5 x 10⁹/l (p=0.02) neutrophil count higher than 0.5 x 10⁹/l (p=0.03) and platelet count higher than 150 x 10⁹/l (p=0.01) were significantly associated to CR/PR achievement. We did not reveal significant differences, when compared to patients that did not achieve a response, in terms of sex, age, hemoglobin level at baseline, bone marrow blast count, cytogenetic profile, IPSS stratification. In conclusions, from our results, based on a large series of patients treated outside clinical trials, it seems that, independently from cytogenetic or hematological subtype, only clinical parameters at baseline could influence the achievement of a good response with azacitidine.