Pb1811: real life application of next generation sequencing in acute myeloid leukemia and high risk myelodysplastic syndrome patients: a single center experience

Topic: 3. Acute myeloid leukemia - Biology & Translational Research Background: Advances in molecular biology have improved understanding and prognostic classification of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), as reflected by the latest ELN recommendations (Dohner, Blood 2022). In addition, persistence of minimal residual disease (MRD) after induction therapy is associated with inferior survival outcomes (Klco, JAMA 2015). However, a conventional MRD marker is available only in around 40% of patients (Ivey, NEJM 2016; Balsat, JCO 2017), and high sensitivity tools are key to improve response evaluation and, eventually, therapeutic algorithms. Aims: 1)To characterize molecular profile of AML and high risk MDS patients by high throughput techniques; 2)To identify prognostic relevance of molecular markers after conventional chemotherapy (CHT) or combination of hypomethylating agents and venetoclax (HMA/VEN) in a real world setting. 3)To prove the applicability of a standard NGS panel at diagnosis and in CR in integrating prognostic stratification of AML Methods: We performed an observational prospective study on AML/MDS patients eligible for CHT or HMA/VEN regimens diagnosed from January 2016 to December 2019 at the Hematology Divisions of the University Hospital “Città della salute e della scienza”, Turin, Italy. Patients were evaluated at diagnosis by conventional bone marrow (BM) histopathology, flow cytometry, cytogenetics/FISH and RTqPCR as well as by next generation sequencing (NGS) on BM or peripheral blood, and treated according to clinical practice. MRD study was performed by flow cytometry and RT-PCR whenever feasible according to current guidelines. Demographic data, disease characteristics at baseline and during follow-up, data on treatment and outcome were collected after obtaining informed consent. The NGS study was performed using the kit Myeloid Solution (MYS) kit by Sophia Genetics on a platform MiSeq Illumina. Results: According to the ELN 2010 classification, the disease risk groups were homogeneously distributed in the cohort. Thirteen patients (15%) were treated with HMA/VEN at diagnosis, while 64 patients received intensive chemotherapy according to age and performance status. Allogeneic stem cell transplantation was performed in 46 patients, 30 of whom were alive after a median follow up of 17 months and 5 patients relapsed after transplantation. The median overall survival and relapse free survival were 13.2 and 7 months, respectively, in patients who did not underwent transplantation. In the transplanted subgroup, the median overall survival was 23.5 months and the median relapse free survival was 16.5 months. Regarding the NGS mutations detected at the diagnosis, genes involved in epigenetic modifications and signaling were found to be the most frequently altered. In particular, DNMT3A, RUNX1, FLT3 NPM1, TET2 and ASXL1 were the most frequently mutated. Summary/Conclusion: In our real life study, NGS was successfully integrated with routine laboratory diagnostics of AML and high risk MDS patients. Genes involved in epigenetic regulation were most frequently mutated. Additional data regarding prognostic significance of such mutations will be presented at the meeting. Keywords: Molecular markers, Myelodysplastic syndrome, Acute myeloid leukemia, Allogeneic stem cell transplant