Abstracts Clinical Lymphoma, Myeloma & Leukemia September 2023 S368 (MDS) patients. Response to these agents is heterogeneous. Our study investigated the impact of type and number of DNA somatic mutations on response to ESAs in a group of low-risk MDS patients revaluated by IPSS-M. Methods: A total of 45 lower-risk MDS patients with symptomatic anemia (Hb < 10 g/dL) and IPSS-R very-low, low, intermediate (score < 3.5) were evaluated. Somatic mutations were evaluated by Ion Torrent-NGS with a panel of 40 genes. The response to ESA (min dose 40.000 U sc/week) was assessed using the 2018 International Working Group (IWG) revised response criteria. Patients were categorized as long responders (>24 months) or short responders (<24 months). Results: All LR MDS IPSS-R patients were re-stratified according to the IPSS-M model. For IPSS-R categories, 23 patients modified their risk category, and 70% were risk-upstaged, while 30% were down-staged for IPSS-R, consistent with previous findings. In the very-low or low IPSS-M categories, 64% of patients achieved erythroid hematologic improvement (HI-E): among them, 41% were long responders, and 21% were short responders. In MDS with moderate low and moderate high IPSS-M categories, only 20% of patients achieved HI-E, 11% were classified as long responders, and 22% as short responders. MDS patients re-stratified to high or very high-risk IPSS-M categories did not achieve a long response to ESA, while 14% achieved a short response. The median number of mutations in this cohort of patients was 3 +/- 1, and the presence of multiple mutations showed a trend with a decreased response to ESA therapy. The mutational burden, assessed by the dominant clone allele frequency (DCAF), did not significantly differ among the response subgroups. Conclusions: Our findings, although analyzed in a limited group of patients, suggest that IPSS-M categories and the number of somatic mutations, but not their VAFs, may impact the rate of response to ESAs. Keywords: MDS, IPSS-M, anemia, ESA, mutational burden MDS-472 Clonal Hematopoiesis in Inflammatory Bowel Diseases Daniel Nathan MD1, Myvizhi Esai Selvan PhD1, Daniela Guisado MD1, Giulia Collatuzzo MD2, Paolo Boffetta MD3,2, Louis Cohen MD1, Zeynep Gümüş PhD1, Bridget Marcellino MD PhD1 1Icahn School of Medicine at Mount Sinai, New York, USA. 2University of Bologna, Bologna, Italy. 3Stony Brook University, Stony Brook, USA Clonal hematopoiesis (CH) is the age-associated acquisition of somatic mutations in hematopoietic stem and progenitor cells. Clonal hematopoiesis of indeterminate potential (CHIP) defines the detection of CH in myeloid associated genes with normal hematologic parameters and it is associated with an increased risk of myeloid neoplasms (MN). Therefore, identifying populations enriched for CH is critical to develop preventative strategies for MN. Inflammatory diseases are increasingly found to be associated with CH and it is hypothesized that the CH clones propagate an inflammatory milieu that is self-reinforcing. One such example is inflammatory bowel disease (IBD) where patients with ulcerative colitis (UC) were found to have enrichment for specific CH genes at older ages when compared to external cohorts; however the risk for CH in Crohn’s disease (CD), or for UC in comparison to internal controls, is unknown. In the present study, we analyzed whole exome sequencing data from the Mount Sinai Crohn’s and Colitis Registry that represents an institutional database of patients with UC, CD, and healthy controls. Our primary aim was to compare rates of CH between each cohort to determine the relationship between IBD and CH. Our hypothesis was that the inflammatory environment of IBD would favor CH, and further that various clinical proxies for disease severity and inflammatory phenotypes would be observed with CH. Secondary aims included whether disease severity correlated with variant allele frequency, and whether the unique inflammatory environments of UC and CD would differentially enrich for CH. Our results showed that, in a single institution registry, the prevalence of CH is increased in UC. Rates of CH increase with age in both UC and the controls, but not in CD. Further, the most frequently mutated genes mirror those seen in a previously reported UC cohort, including DNMT3A and PPM1D. Multivariable associations between IBD phenotype and CH are ongoing. In conclusion, we confirmed that patients with IBD are a high-risk population for CH, raising concern for the risk of inflammatory-mediated clonal expansion and providing rationale for screening programs in IBD patients to identify CH and those at risk for progression to MN. Keywords: MDS, clonal hematopoiesis, clonal hematopoiesis of indeterminate potential, inflammatory bowel disease, ulcerative colitis, Crohn’s disease MDS-488 Magrolimab Alters the Tumor Microenvironment to Improve Bone Marrow Functions in Patients With Acute Myeloid Leukemia (AML) and Higher‑Risk Myelodysplastic Syndromes (HR‑MDS) Lisa Johnson MBA, PhD1, Yajia Zhang PhD1, Linda Su-Feher PhD, BS1, Yeonju Lee PhD1, David A. Sallman MD2, Adam S. Asch MD3, Monzr M. Al Malki MD4, Hyunjae Ryan Kim PhD1 1Gilead Sciences Inc, Foster City, USA. 2Moffitt Cancer Center, Tampa, USA. 3University of Oklahoma Health Sciences Center, Oklahoma City, USA. 4City of Hope National Medical Center, Duarte, USA Background: Magrolimab (Hu5F9-G4) is a monoclonal antibody blocking CD47, a “don’t eat me” signal on tumor cells. Azacitidine (AZA) increases tumor expression of prophagocytic signals, synergizing with magrolimab to facilitate phagocytosis by macrophages. CD47 blockade also has the potential to trigger innate/adaptive immune antitumor activity within the bone marrow environment. We analyzed the pharmacodynamic and immune effects of magrolimab+AZA in the bone marrow microenvironment in patients with untreated HR-MDS/AML in a phase Ib trial (NCT03248479). Methods: Patients received magrolimab (1 mg/kg priming dose) intravenously on days 1 and 4, then 30 mg/kg weekly or biweekly as maintenance, in 28-day cycles. AZA 75 mg/m2 was
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