96 OVERALL SURVIVAL IN OLDER PATIENTS WITH NEWLY DIAGNOSED AML WITH >30% BONE MARROW BLASTS AND POOR-RISK CYTOGENETICS TREATED WITH AZACITIDINE: SUBANALYSIS OF THE AZA-AML-001 STUDY

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Rating Scale for Geriatrics (CIRSG). Univariable and multivariable survival analyses were performed using Cox’s proportional hazards regression models. Results: 129 patients were included in the analysis. Median age was 79,5 years [IQR 77.3-83.3]. Diagnosis was refractory cytopenia with multilineage dysplasia (RCMD) in 2 patients (1.5%), chronic myelomonocytic leukemia 2 (CMML2) in 14 patients (10.9%), refractory anemia with excess blasts 1 (RAEB1) in 5 patients (3.9%), RAEB2 in 24 patients (18.6%), acute myeloid leukemia (AML) with 20-30% bone marrow blasts in 33 patients (25.6%) and AML with ≥ 30% bone marrow blasts in 51 patients (39.5%). Patients received a median of 8 cycles [IQR 4-16] and therapeutic response according to IWG2006 criterias was obtained in 55 patients (42.6%). Median overall survival was 13.5 months [CI95% 9.6-16.4]. Age (HR=1.06[1.01-1.11]), adverse cytogenetics (HR=2.15[1.423.25]), peripheral circulating blasts (HR=2.53[1.61-3.98]), and comorbidities measured by the Cumulative Illness Rating Scale for Geriatrics (CIRSG) (HR=1.27[1.11-1.45]) independently predicted poorer OS. Response after 6 cycles was an independent factor for better OS (HR=0.29 [0.16-0.52]). Conclusion: Comorbidities have a negative impact on overall survival in the elderly with high risk MDS or AML treated with azacitidine. Prognosis factors based on disease status remain crucial in this population.

95 MDS: AN INTEGRATED WORKUP FOR A CORRECT DIAGNOSIS E. Ciabatti1, M. Ferreri2, A. Valetto2, V. Bertini2, A. Guazzelli2, A. Azzarà3, I. Petrini4, F. Guerrini3, S. Grassi3, M. Metelli3, P. Simi2, M. Petrini3, S. Galimberti3 1 Department of Clinical and Experimental Medicine, Azienda Ospedaliero-Universitaria Pisana and University of Siena (GenOMec), Pisa, Italy; 2Department of Laboratory Medicine, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; 3Department of Clinical and Experimental Medicine, Azienda OspedalieroUniversitaria Pisana Hematology, Pisa, Italy; 4Department of Clinical and Experimental Medicine, Azienda Ospedaliero-Universitaria Pisana Oncology, Pisa, Italy Background and aim: The diagnosis of MDS is determined by bone marrow’s histology and is integrated by conventional cytogenetic (CC) analyses that, although, are unable to show chromosomal abnormalities in about 30% of cases. Array Comparative Genomic Hybridization (aCGH) detects copy number aberrations in half of MDS diploid by CC. Recently, TET2, ASXL1, EZH2, CBL, IDH1/IDH2, DNMT3A, and UTX mutations have been described in MDS. Therefore, we evaluated the prognostic and predictive implications of FISH, aCGH and mutation assays when added to CC. Patients and methods: Fifty patients, 15 females and 35 males, with a median age of 72-year (range 39-88) were enrolled in a single institution (Hematology Unit of University of Pisa, Italy), between March 2013 and October 2014. Patients’ prognosis was determined according to IPSS in low (42%), intermediate-1 (33%), intermediate-2 (17%) and high risk (8%). Samples were evaluated by CC including, conventional karyotyping and FISH for chromosome 5, 7, PDGFRA, and PDGFRB. Moreover, aCGH was performed using SurePrint G3 Human CGH Microarray, 8x60K (Agilent), and mutations of TET2, TP53, ASXL1, and EZH2 were determined using qBiomarker somatic mutation PCR array (Qiagen). Results: Table 1 summarizes CC results. Using FISH, additional copy number losses of chromosome 7 and 5 were observed in 1 and 2 cases, respectively. According to aCGH, 20 patients (40%) showed copy number aberrations (Table 2). Seventeen patients had a mutation: 12 in TP53, 4 in ASXL1 and 1 in TET2 sequence.

Conclusions: 1) The study showed the reduction of CC failures (only 16%); 2) Because of FISH results, a patient received azacitidine and another one lenalidomide; 3) Three MDS patients with copy number aberrations detected exclusively by aCGH progressed in acute leukemia being lethal: one patient had copy number loss of chromosome 3, one had copy number losses of chromosomes 8 and Y and the last one had copy number loss of ETV6 locus; 4) One patient with TET2 mutation did not respond to the azacitidine. Three out of 4 patients with ASXL1 mutation had a good response to epoietin. TP53 mutations were observed in 12 cases of which 2 developed acute leukemia, 2 were resistant, and 2 sensitive to epoetin. In conclusion, our results support the relevance of an integrated work-up for MDS and provide a preliminary estimation of copy number aberration and mutation frequencies. The prognostic role of aCGH and somatic mutations needs to be determined in properly sized series.

96 OVERALL SURVIVAL IN OLDER PATIENTS WITH NEWLY DIAGNOSED AML WITH >30% BONE MARROW BLASTS AND POOR-RISK CYTOGENETICS TREATED WITH AZACITIDINE: SUBANALYSIS OF THE AZA-AML-001 STUDY H. Döhner1, J.F. Seymour2, A. Butrym3, A. Wierzbowska4, D. Selleslag5, J.H. Jang6, J.D. Cavenagh7, R. Kumar8, A.C. Schuh9, A. Candoni10, C. Récher11, I. Sandhu12, T. Bernal del Castillo13, H.K. Al-Ali14, G. Martinelli15, J. Falantes16, R. Nopenney17, R.M. Stone18, M.D. Minden9, H. McIntyre19, S. Songer19, L.M. Lucy20, C.L. Beach19, H. Dombret21 1 Department of Internal Medicine III, Universitätsklinikum Ulm, Ulm, Germany; 2Department of Haematology, PeterMacCallum Cancer Centre, East Melbourne, Australia; 3Department of Haematology Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, Poland; 4Department of Hematology, Medical University of Lodz, Lodz, Poland; 5Division of Hematology, AZ Sint-Jan Brugge-Oostende, Brugge, Belgium; 6Division of Hematology-Oncology, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, Korea; 7Department of Haematology, St Bartholomew’s Hospital, London, United Kingdom; 8 Department of Medical Oncology and Haematology, CancerCare Manitoba, Winnipeg, Canada; 9Malignant Hematology, Princess Margaret Cancer Centre, Toronto, Canada; 10Division of Hematology and Bone Marrow Transplantation Unit, Azienda Ospedaliero Universitaria S. Maria della Misericordia di Udine, Udine, Italy; 11 Département d’hématologie, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse, France; 12Department of Oncology, University of Alberta Hospital, Edmonton, Canada; 13Department of Hematology, Hospital Central de Asturias, Oviedo, Spain; 14Division of Hematology and Oncology, University Hospital Leipzig, Leipzig, Germany; 15Department of Hematology and Oncology, Institute of Hematology and Medical Oncology “L. e A. Seràgnoli”, Bologna, Italy; 16Department of Hematology, Hospital Universitario Virgen del Rocio/Instituto de BioMedicinia de Sevilla, Seville, Spain; 17 Department of Hematology, Universitätsklinikum Essen Klinik für Hämatologie, Essen, Germany; 18Department of Medicine, DanaFarber Cancer Institute, Boston, USA; 19Clinical Development, Celgene Corporation, Summit, USA; 20Department of Biostatistics, Celgene Corporation, Summit, USA; 21Department of Hematology, Hôpital Saint Louis, Paris, France Background: Overall survival (OS) in older patients with AML and poor-risk cytogenetics is only ~2-3 months (Burnett, 2007). Often these patients receive only best supportive care (BSC). Low-dose cytarabine (LDAC) and induction chemotherapy (IC) provide no OS benefit for these patients (Döhner, 2010; Kantarjian, 2010). The

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hematologic adverse event rates were consistent with the known safety profile of azacitidine in patients with MDS (Fenaux, 2009). Conclusions: In older patients with AML and poor-risk cytogenetics, treatment with azacitidine prolonged median OS and increased 1-year survival probability compared with CCR. Thus, azacitidine may be the preferred treatment option for these difficult-to-treat patients.

Fig. 1. Preselection and randomization of patients with poor-risk cytogenetics.

Fig. 2. Overall and 1-year survival.

international, phase 3 AZA-AML-001 study compared azacitidine with conventional care regimens (CCR) in older patients (≥65 years) with newly diagnosed AML (>30% marrow blasts). Objective: To determine the effects of azacitidine vs CCR on OS and 1-year survival in patients with poor-risk cytogenetics in the AZA-AML-001 study. Methods: Before randomization, each patient was preselected to receive a commonly used CCR for older patients with AML, per investigator choice (Figure 1). Patients were then randomized to azacitidine or CCR, in which case they received their preselected treatment. Cytogenetic risk (NCCN criteria) was assessed by central review. Poor-risk cytogenetics included complex karyotype (≥3 abnormalities); -5 or 5q-; -7 or 7q-; t(v;11q23); inv(3) or t(3;3); and t(6;9). Results: Of 488 randomized patients, 170 (35%) had poor-risk cytogenetics (azacitidine n=85 [35%]; CCR n=85 [34%]). Median ages in the azacitidine and CCR groups, respectively, were 76 years (range 44-90) and 74 years (65-87); 28% and 26% had ECOG PS score of 2; and 21% and 19% had had prior MDS. Median OS was prolonged with azacitidine vs CCR for all patients with poor cytogenetics (6.4 vs 3.2 months, P=0.0185; Figure 2A), and twice the proportion of azacitidine-treated patients were alive at 1 year vs. CCR patients (30.9% vs 14.0%, respectively; D16.9%; 95%CI 4.4, 29.5). Median OS was also increased with azacitidine vs LDAC in the subgroup of patients with poor-risk cytogenetics preselected to receive LDAC (7.7 vs 4.3 months, P=0.0900; Figure 2B). Grade 3-4

97 CHARACTERISTICS OF ROMIPLOSTIM-TREATED MDS PATIENTS WITH HEMATOLOGIC IMPROVEMENT IN PLATELETS (HI-P) P. Fenaux1, P. Muus2, H. Kantarjian3, R.M. Lyons4, R.A. Larson5, M.A. Sekeres6, P.S. Becker7, A. Orejudos8, J. Franklin9 1 Service d’Hématologie Clinique, Hôpital Avicenne Université Paris XIII, Bobigny, France; 2Department of Hematology, Radboud University Medical Center, Nijmegen, Netherlands; 3Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, USA; 4Department of Hematology, Cancer Care Centers South Texas/US Oncology, San Antonio, USA; 5Department of Medicine, University of Chicago, Chicago, USA; 6Hematology and Oncology, Cleveland Clinic Taussig Cancer Center, Cleveland, USA; 7Division of Hematology, University of Washington, Seattle, USA; 8Global Biostatistical Science, Amgen Inc., Morganville, USA; 9 Hematology/Oncology, Amgen Inc., Thousand Oaks, USA Background: Thrombocytopenia occurs in 40%–65% of MDS patients. Romiplostim increases platelet counts and decreases bleeding in MDS. We examined romiplostim-treated MDS patients achieving HI-P per IWG 2006 criteria for 8 weeks (baseline >20×109/L: increase ≥30×109/L; baseline <20×109/L: increase to ≥20×109/L and by ≥100%). Methods: Thrombocytopenic IPSS low/int-1 risk MDS patients received romiplostim at fixed doses (300-1500 g) in two phase 2 trials (NCT00303472, NCT00614523) and in doses (250-1500 g) adjusted for platelet counts in an open-label extension (NCT00472290), weekly or every other week, and generally subcutaneously (intravenously in one study arm). A post hoc analysis was performed on the 34 of 60 romiplostim-treated patients achieving HI-P. Results: 53% of the 34 patients achieving HI-P were women, 82% were white, and median (Q1, Q3) age was 70 (65, 78) years. WHO category at diagnosis was RCMD (41%), RA (32%), unclassified (15%), RAEB-1 (6%), RARS (3%), and del(5q) (3%). IPSS status was low (29%), int-1 (65%), or unknown (6%). Median (Q1, Q3) baseline

Fig. 1.