Azacitidine Overcomes Prognosis Impact of Poor and Very Poor IPSS-Revised in RAEB-2 Patients but Not in AML Patients.
Authors: Cluzeau Thomas , Mounier Nicolas , Richez Valentine , Karsenti Jean-Michel , Legrand Faezeh , Mannone Lionel , Vinti Henri , Legros Laurence , Gastaud Lauris , Thyss Antoine , Garnier Georges , Re Daniel , Montagne Nathalie , Gutnecht Jean , Auberger Patrick , Raynaud Sophie , Cassuto Jill-Patrice 
Published: October 2019

Abstract
Abstract 2813

Background:
Myelodysplastic syndroms (MDS) are an heterogenous diseases. In order to define prognosis of differents subgroups, several scoring are elaborated. The most used was IPSS score including pourcentage of blasts, number of cytopenia and cytogenetics. Recently, IPSS was revised. IPSS-R includes new cytogenetics subgroups, anemia, thrombocytopenia, neutropenia and pourcentage of blasts. These score were defined in untreated MDS and Acute Myeloid Leukemia (AML) with less 30% of blasts patients. IPSS-R score was evaluated in MDS untreated population included AML with 20–29% of blasts. Only 16% of patients were higher-risk IPSS MDS in this study (Greenberg et al., Blood 2012). Azacitidine (AZA) prolongs survival when used as first line treatment of higher-risk MDS and AML with 20–29% bone marrow (BM) blasts (Fenaux et al., Lancet Oncology 2009). The aim of this study is to evaluate efficacy of AZA in higher IPSS-R MDS and AML with 20–99% BM blasts.

Methods:
We analyzed retrospectively MDS and AML patients treated by AZA in 6 centers. Patients having received ≥ 1 cycle of AZA and who had BM evaluation after ≥ 4 cycles, or who died or progressed before completion of 4 cycles were considered évaluable (the last 2 groups were considered as treatment failures). Responses were scored according to IWG 2006 criteria for MDS and to Cheson et al. (JCO 2003) for AML.

Results:
The study population included 149 patients: F/M: 65/84; median age 70 (range 35–88). Median number of cycle of AZA treatment was 6 (range 1–42). Diagnosis at AZA was (RAEB-1 n=1, RAEB-2 n=69, AML n=79). Median overall survival (OS) was 11 months. For MDS population excluding AML with 20–29% of blasts, IPSS score was intermediate-1 in 16 patients, intermediate-2 in 29 patients and high in 25 patients. In using IPSS-R score, we observed IPSS-R good in 2 patients, IPSS-R intermediate in 20 patients, IPSS-R poor in 29 patients and IPSS-R very poor in 19 patients. If we applied IPSS-R score in WHO-AML population, we observed IPSS-R intermediate in 11 patients, IPSS-R poor in 39 patients and IPSS-R very poor in 29 patients. In all cohort population, we observed a significant difference in median OS between « intermediate + poor » group versus very poor group (12 months vs 9 months respectively, p=0.01). In MDS sub group analysis excluding AML with 20–30% of blasts, we observed no significant difference in median OS between these 2 groups (13 months vs 9 mois respectively, p=0.39). Nevertheless, we still observed a significant difference in median OS between these 2 groups in AML population (12 months vs 6 months respectively, p=0.02).

Conclusion:
Our results suggest that AZA cancels prognostic impact of IPSS-R score in MDS patients treated by AZA. IPSS-R score could be applied in AML population and keep his prognostic impact in AML patients treated by AZA. IPSS-R score should be evaluated in larger cohort of MDS and AML patients treated by AZA in order to confirm these results.

Disclosures:
No relevant conflicts of interest to declare.