comprising of elderly patients. Two patients in the 100 mg asunercept dose group experienced a serious adverse event with a suspected relationship to asunercept. The incidence of disease progression was low in this study with three patients experiencing an increase in medullary blast count. However, in one of the bone marrowexamination occured during treatment with G-CSF due to neutropenic septic complications, i.e. increase in bone marrow blasts was rather related to G-CSF stimulation. Regarding efficacy as a secondary objective, the absolute number of transfused packed red blood cells (pRBC) during treatment phase was compared to the first and second 12 week post treatment periods in patients who completed the end-of-study visit (n = 15). In 8 of 15 patients a decrease in absolute pRBC number by 3 was found. In a post-hoc analysis, three patients fulfilled the criteria for erythroid response per modified IWG criteria when pre-study transfusion burden was compared to post-treatment periods. In conclusion, asunercept was very well tolerated and showed efficacy in a subset of transfusion-dependent MDS patients. It is a promising compound with a new mechanism of action that warrants for further clinical investigation, particularly in combination with erythropoiesis stimulating agents. 85 RESULTS OF A PHASE II STUDY OF GUADECITABINE IN HIGHER RISK MDS PATIENTS REFRACTORY TO OR RELAPSING AFTER AZACITIDINE TREATMENT M. Sebert 1 , C. Bally 1 , P. Peterlin 2 , O. Beyne-Rauzy 3 , L. Legros 4 , M.P. Gourin 5 , L. Sanhes 6 , E. Wattel 7 , E. Gyan 8 , S. Park 9 , A. Stamatoullas 10 , K. Laribi 11 , A. Banos 12 , S. Jueliger 13 , S. Chevret 14 , L. Ades 1 , P. Fenaux 1 1 Hematologie Clinique, Hopital Saint-Louis, PARIS, France; 2 Hematologie Clinique, CHU de Nantes, Nantes, France; 3 Hématologie Clinique, IUCT ONCOPOLE Toulouse, Toulouse, France; 4 Hématologie Clinique, CHU de Nice, Nice, France; 5 Hématologie Clinique, CHRU de Limoges, Limoges, France; 6 Hématologie Clinique, CHU de Perpignan, Perpignan, France; 7 Hématologie Clinique, CHU Lyon Sud, Lyon, France; 8 Hématologie Clinique, CHRU de Tours, Tours, France; 9 Hématologie Clinique, CHU de Grenoble, Grenoble, France; 10 Hématologie Clinique, Centre Henri Becquerel, Rouen, France; 11 Hématologie Clinique, CHU Côte de Nacre, Caen, France; 12 Hématologie Clinique, CH de la côte Basque, Bayonne, France; 13 Astex, Cambridge Science Park, Cambridge, United Kingdom; 14 Biostatistiques, Hopital Saint-Louis, Paris, France Background: Guadecitabine is a novel HMA dinucleotide of Decitabine and deoxyguanosine, administered SC, which results in extended DAC exposure. We designed a national multicenter phase II study evaluating the efficacy of Guadecitabine in higher- risk MDS patients, refractory or relapsing after AZA (NCT02197676). Methods: Main inclusion criteria were (1) IPSS int-2 or high MDS, or CMML with WBC < 13 G/L and marrow blasts >10%, or AML with 20–30% marrow blasts (2) Refractory to 6 cycles of AZA or relapsing after response. Patients received GDAC 60 mg/m 2 /d ×5 d every 28 d. Results: Between Aug 2014 and Jan 2016, 56 pts from 13 centers were enrolled, M/F: 37/19, median age 75 years [IQR, 69–76]. At inclusion, WHO classification was RCMD in 2 pts, CMML in 1 pt, RAEB-1 in 11 pts, RAEB-2 in 31 pts and AML in 11 pts. R-IPSS was low, int., high and very high in 1 (2%), 3 (6%), 13 (26%), and 34 (60.7%) pts resp (5NA). 43 (77%) pts were RBC transfusion- dependent and ECOG was >1 in 5(9%) pts. The average baseline LINE-1 methylation level was 73% in blood and 72% in BM. 55 patients received at least one cycle of GDAC, with a median of 3 cycles [IQR, 2–5.5]. 9 pts responded with 1 CR, 2 CRp, 5 marrow CR and 1 HI; ORR of 16% (95%CI, 8–28%). Responses were seen in 4/15 (26.6%) primary refractory, and in 5/41(12.2%) relapsing patients (p = NS). Median duration of response was 9 months including so far 2 responses ≥1.5 years. 49 SAE occurred in 44 pts, and were mostly hematological. 49 patients ended the study, because of progression (n = 20), death (n = 14), investigator or patient decision (n = 8), toxicities (n = 6) and pt withdrawal (n = 1). Median OS from inclusion was 6.7 months (IC95% [5.6–11.8]). 33 pts had died, because of MDS progression in 14 (42%), infection in 13 (39.3%), bleeding in 1 (3%), and other causes in 5 (15%) pts. No significant prognostic factor of response to GDAC was found. OS was significantly shorter in pts with high IPSS (HR = 2.1, 95%CI, 1.04– 4.20, p = 0.04), and with very poor IPSS-R cytogenetics (HR = 4.3, 95%CI, 2.0–9.1, p =0.0015), the latter remaining prognostic in multivariate analysis. Conclusion: Response rates with GDAC, in this population of higher risk MDS, CMML or low blast count AML with failure to AZA (and often with IWG 2006 progression) were modest. Tolerance was similar to that of conventional HMA treatment. 86 MOLECULAR CHARACTERIZATION OF HIGH-RISK MDS PATIENTS TREATEDWITH AZACITIDINE AND LENALIDOMIDE: ROLE OF INOSITIDE-DEPENDENT SIGNALLING, MUTATIONS AND MICRORNA M.Y. Follo 1 , A. Pellagatti 2 , R.N. Armstrong 2 , S. Mongiorgi 1 , A. Astolfi 3 , V. Indio 3 , S. Ratti 1 , C. Clissa 4,5 , M. Barraco 4 , S. Parisi 4 , L. Manzoli 1 , A. Pession 6 , L. Cocco 1 , J. Boultwood 2 , C. Finelli 4 1 Human Anatomy, Biomedical and Neuromotor Sciences- University of Bologna, Bologna, Italy; 2 Bloodwise Molecular Haematology Unit, Nuffield Division of Clinical Laboratory Sciences- Radcliffe Department of Medicine- University of Oxford- John Radcliffe Hospital, Oxford, United Kingdom; 3 “Giorgio Prodi” Cancer Research Center, University of Bologna, Bologna, Italy; 4 Institute of Hematology “LeA Seràgnoli”, University of Bologna, Bologna, Italy; 5 Hematology and Stem Cell Transplant Center, San Salvatore Hospital- Pesaro, Pesaro, Italy; 6 Hematology-Oncology Unit, Department of Pediatrics “Lalla Seràgnoli”- Sant’Orsola-Malpighi Hospital- University of Bologna, Bologna, Italy Background: Several clinical studies demonstrated the efficacyand safety of combining azacitidine with lenalidomide in Myelodys- plastic Syndromes (MDS), but the molecular implications of this therapy (i.e. gene mutations and microRNA profiling) are still under investigation. Moreover, phosphoinositide-specific phospholipase C (PI-PLC) beta1 is modulated in MDS cells treated with azacitidine, whereas lenalidomide, restoring a normal erythropoiesis, can affect PI-PLCgamma1 pathways. Purpose: This study firstly aimed to assess the effect of azacitidine and lenalidomide combination therapy on the expression of inositide-dependent signalling, focusing particularly on PI-PLC isoenzymes. Moreover, an extensive analysis on gene mutations and microRNA expression profiling was also performed. Patients and Methods: This study included 44 patients diagnosed with high-risk MDS who were given azacitidine and lenalidomide. Paired samples, before and during treatment, were analyzed. Firstly, we quantified the expression of PI-PLC isoenzymes by Real-Time PCR and immunocytochemical experiments. Moreover, we carried out cell cycle analyses and studied both PI-PLCbeta1 methylation status and the expression of Globin genes. In addition, the frequency of recurrent gene mutations associated with myeloid malignancies was evaluated, using an Illumina Cancer Myeloid Panel, and the expression of microRNAs was assessed using an Affimetrix array. Results: In our case series, 34/44 patients completed at least 6 cycles of treatment and were clinically evaluable, with an overall response rate of 76.5% (26/34 cases). Firstly, the therapy affected Poster Presentations – 14th International Symposium on Myelodysplastic Syndromes / Leukemia Research 55 S1 (2017) S45–S167 S54