OP-017 The Presence of MDS-like Phenotypic Abnormalities (MDS-PA) Identifies Newly Diagnosed Multiple Myeloma (MM) Patients With MDS/AML- Related Somatic Mutations And Inferior Survival Bruno Paiva, 1 Noemi Puig, 2 Maria-Teresa Cedena, 3 Iria Vazquez, 4 Maria-Carmen Chillon, 2 Yanira Ruiz, 3 Joaquin Martinez-Lopez, 3 Ramon Garcia-Sanz, 2 Marcos Gonzalez, 2 Xabier Agirre, 4 Maria-Jose Calasanz, 4 Leire Burgos, 4 Diego Alignani, 4 Felipe Prosper, 4 Sergio Matarraz, 2 Alberto Orfao, 2 Albert Oriol, 5 Ana Isabel Teruel, 6 María-Asunción Echeveste, 7 Raquel de Paz, 8 Felipe de Arriba 9 1 University of Navarra, Pamplona; 2 Hospital Universitario Salamanca; 3 Hospital 12 Octubre; 4 University of Navarra; 5 Hospital Germans Trias i Pujol; 6 Hospital Clínico Universitario de Valencia; 7 Hospital Uni- versitario Donostia, Spain; 8 Hospital Universitario La Paz; 9 Hospital Morales Meseguer Long-term complications including SPMs such as MDS and AML are becoming new challenges in designing optimal patient care. Thus, there is need to investigate for biomarkers that uncover cellular alterations predisposing for higher risk of MDS/AML in MM. Here, we started by investigating in 312 newly diagnosed MM patients the presence of MDS-PA in BM neutrophil, mono- cytic, and erythroid lineages, using multidimensional flow cytom- etry. Up to 33/312 (11%) patients showed MDS-PA at diagnosis, which were observed in the neutrophil lineage (6%), followed by monocytic (4%) and erythroid (4%) lineages. Afterwards, we investigated if the presence of MDS-PA was associated with un- derlying somatic mutations (sSNV) by performing targeted sequencing of 54 MDS/AML related genes (depth 500x) in 44 patients from the previous series (10 with MDS-PA and 34 without). NGS was performed in FACS sorted CD34+ HSCs and dysplastic cell lineages from patients with MDS-PA, as well as in HSC from cases without MDS-PA. CD138+ BM PCs from both cohorts were also sequenced using the same panel. Six out of the 10 cases with MDS-PA showed sSNV. Namely, HSCs from one pa- tient had two sSNV in TET2 one in CALR and another in ASXL1. A second patient had NPM1 mutated in HSCs. A third case had TET2 mutated in HSCs as well as in dysplastic monocytes and neutrophils. In the fourth case, a sSNV in BCORL1 was noted in dysplastic erythroid cells. The fifth patient had TET2 mutated in both HSCs and dysplastic monocytes. The sixth case had PHF6 mutated in HSCs. In none of the patients were the sSNV found in HSCs and/or dysplastic lineages, present in PCs. Within the control cohort of the 34 patients without MDS-PA, only two of them displayed sSNV in HSCs; one case had DNMT3A mutated and the other TET2. After demonstrating a correlation between MDS-PA and MDS/AML-related sSNV, we sought to analyze its prognostic significance. Thus, we focused on a large series of 965 patients with longer follow up (median of 6.5 years) enrolled in GEM clinical trials, and for which the presence of CD56+ aberrant monocytes could be investigated. As compared to the overall MM population, patients with MDS-PA (n¼63; 6.5%) showed significantly higher age, lower hemoglobin values and higher BMPC infiltration at diagnosis. Furthermore, they experienced more frequently hema- tological toxicity including anemia and neutropenia during treat- ment. Most interestingly, as compared to the overall MM population, patients with MDS-PA had significantly inferior PFS and OS. We showed for the first time that a fraction of MM pa- tients harbors MDS/AML-related sSNV, and that such patients could be predicted through flow-based screening for MDS-PA. The presence of MDS-PA identifies a subset of patients that experience more frequently hematological toxicity and display inferior survival; accordingly, screening for MDS-PA could become an important biomarker to tailor treatment in MM. OP-018 A More Mature Immunophenotypic Make-up of Multiple Myeloma Clone(s) at Diagnosis Correlates With a Higher Genomic Instability Marina Martello, 1 Barbara Santacroce, 2 Enrica Borsi, 3 Rosalinda Termini, 2 Vincenza Solli, 2 Lucia Pantani, 2 Elena Zamagni, 4 Paola Tacchetti, 2 Francesca Ulbar, 2 Mario Arpinati, 2 Gabriella Chirumbolo, 2 Giovanni Martinelli, 2 Michele Cavo, 5 Carolina Terragna 2 1 DIMES-Institute of Hematology, Bologna, BO; 2 DIMES-Institute of Hematology; 3 Fondazione Umberto Veronesi; 4 Azienda Ospedaliero- Universitaria Policlinico S. Orsola, Malpighi, Bologna, Italy; 5 Bologna University School of Médicine, Seragnoli Institute of Hematology The sequence of events underlying the Multiple Myeloma (MM) plasma cells (PC) differentiation have not yet fully elucidated, even if recent findings suggest that different cell subpopulations, with distinct phenotype, compose the MM clone(s), whose plasticity has emerged as a typical feature. Aim of the study was to evaluate the phenotypic plasticity and genomic background of MM clone(s) at diagnosis in order to stratify patients (pts) according to the PC differentiation stages and to evaluate the impact of this stratification on the disease outcome. Phenotypic characterization of both CD138+/CD38+ and CD19+ populations was carried out on 44 newly diagnosed MM. Fresh BM samples was analysed by 6-color multiparametric flow citometry analysis, combining CD138-PE, CD38-PE-Cy7, CD20-APC, CD19-APC-Cy7, CD27-FITC, CD45-FITC, CD28-APC, CD44-FITC, CD54-APC, CD81- PerCP-Cy5.5, CD56-APC and SHH-PE, as a functional marker of Hedgehog pathway activation. Cytoscan HD array were carried out in order to detect genomic copy number alterations (CNAs). Ac- cording to the CD19 and CD81 markers co-expression, pts were stratified in 3 different subgroups, recapitulating a progressive PC maturation process: the most immature one, including pts with CD19+/CD81+ PC (11/44 ¼ 25%); the intermediate CD19-/ CD81+ phenotype one (19/44 ¼ 43%), and the CD19-/CD81- PC Abstracts 16 th International Myeloma Workshop, March 1-4, 2017 - e11