Abstracts Clinical Lymphoma, Myeloma & Leukemia September 2023 S366 absolute neutrophil count of .95, a hemoglobin of 8.5, and platelet count of 24; 34/51 patients (67%) required packed red blood cell transfusion and 35/51 (69%) required platelet transfusion. Bone marrow cellularity was <10% in 26/48 patients (54%). Twenty-two patients were tested for large granular lymphocyte (LGL) clones, and 12 (55%) had clones present. Paroxysmal nocturnal hematuria (PNH) clones were detected in 22 out of the 42 patients tested (52%). T-cell clones were found in 20 out of 26 patients (77%). First line therapy details were available for 49 patients, with a further 2 patients under observation. The most used first line therapies were equine ATG (eATG) + cyclosporine (CSA) + eltrombopag in 15, followed by eATG + CSA in 9, and eltrombopag only in 7. All 7 patients receiving eltrombopag only first line had no response. In patients receiving eATG/CSA with or without eltrombopag 9/24 (38%) had partial response and 7/24 (29%) had complete response; 1 patient did not have follow up data. No difference in response was observed between triple therapy incorporating eltrombopag compared to eATG/CSA alone. No difference in response was noted based on presence of LGL clone or PNH clone. Nine received allogeneic stem cell transplant (allo-SCT): 3 received it second line, 3 received it third line, and 3 received it fourth line or greater. Median overall survival was not reached in our cohort. Conclusions: AA is diagnosed primarily in symptomatic patients requiring transfusions with life threatening cytopenias. First treatment varies, but the most common therapies, which rely on eATG and CSA had shown the most success. Patients often require multiple lines of treatment. Keywords: MDS, aplastic anemia, paroxysmal nocturnal hematuria, ATG, cyclosporine, eltrombopag MDS-432 Challenges in Diagnosis and Treatment of VEXAS Syndrome: Two Case Reports Sonia Raj MBBS, Sonali Sadawarte MD Royal Hobart Hospital, Hobart, Australia Context: VEXAS (Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently discovered adult-onset syndrome that links haematological and autoimmune symptoms. It typically affects older males and occurs due to a mutation in the UBA1 gene. We describe 2 cases at our institution. Case Report: A 70-year-old man, with refractory and relapsing polychrondritis and a history of interstitial lung disease was on immunosuppression including prednisolone and methotrexate when he developed macrocytic anaemia, thrombocytopenia, and Sweet syndrome. A bone marrow biopsy was performed in the setting of refractory polychrondritis, difficult steroid wean and worsening cytopenias; the morphology was suggestive of VEXAS with myeloid vacuolization, and this was confirmed on molecular testing with mutation in UBA1 gene. He was treated with prednisolone and tocilizumab and continued to have aggressive flares of polychondritis and Sweet syndrome. Azacitidine was delivered with the aim to target the UBA1 mutant clone. Profound thrombocytopenia limited the use of ruxolitinib. There was no clinical improvement; he died due to infection 12 months following the diagnosis of VEXAS. Case Report: A 76-year-old gentleman had seronegative inflammatory arthritis causing severe pain; he was commenced on methotrexate and prednisolone. Five months post- diagnosis of inflammatory arthritis, he developed an unprovoked deep-vein-thrombosis. Following this, his health declined with macrocytic anaemia, despite cessation of methotrexate as well as bilateral pleural effusions requiring chest drains. In early 2022, a bone marrow biopsy was performed, and this showed myelodysplastic syndrome (MDS) with multilineage dysplasia. Cytoplasmic vacuolation was noted in the erythroid precursors. Molecular testing confirmed UBA1 variant and DNMT3A variant (variant allele frequency, 44%). As the MDS was in the Revised International Prognostic Scoring System low risk category, he was managed conservatively. He subsequently developed cholecystitis and sepsis, leading to death 4 months after the diagnosis of VEXAS. Conclusions: These cases highlight the non-haematological clinical features and therapeutic challenges associated with VEXAS syndrome, including pleural effusions, thrombosis, and Sweet syndrome. The co-existence of other somatic mutations with UBA1, such as DNMT3A has been reported in 9.2%–22% of cases and is of unclear significance. This may represent coincidental age-related clonal haematopoiesis. Earlier diagnosis and close collaboration within a multi-disciplinary team is crucial. Keywords: VEXAS, myelodysplastic syndrome, case MDS-457 Ivosidenib in Mutant IDH1 Relapsed/ Refractory Myelodysplastic Syndrome: Updated Substudy Results Courtney D. DiNardo MD1, Gail J. Roboz MD2, Justin M. Watts MD3, Yazan F. Madanat MD4, Gabrielle T. Prince MD5, Praneeth Baratam MBBS6, Stéphane de Botton MD7, Anthony Stein MD8, James M. Foran MD9, Martha L. Arellano MD10, David A. Sallman MD11, Dylan M. Marchione PhD12, Xiaofei Bai PhD12, Prapti A. Patel MD12, Stephanie M. Kapsalis OTR12, Guillermo GarciaManero MD1, Amir T. Fathi MD13 1University of Texas MD Anderson Cancer Centre, Houston, USA. 2Weill Cornell Medicine and The New York Presbyterian Hospital, New York, USA. 3University of Miami, Sylvester Comprehensive Cancer Center, Miami, USA. 4University of Texas Southwestern Medical Center, Dallas, USA. 5Johns Hopkins Hospital, Baltimore, USA. 6Medical University of South Carolina, Charleston, USA. 7Institut Gustave Roussy, Villejuif, France. 8City of Hope, Duarte, USA. 9Mayo Clinic, Jacksonville, USA. 10Winship Cancer Institute, Emory University School of Medicine, Atlanta, USA. 11Moffitt Cancer Center, Tampa, USA. 12Servier Pharmaceuticals LLC, Boston, USA. 13Massachusetts General Hospital Cancer Center, Boston, USA Context: Patients with mutant isocitrate dehydrogenase 1 (mIDH1) relapsed/refractory myelodysplastic syndrome (R/R MDS) have poor outcomes following failure of hypomethylating agents (HMA). Ivosidenib (IVO) is a potent, oral, targeted mIDH1 inhibitor. In the first-in-human IVO study (NCT02074839), objective response rate (ORR) was 75% (complete remission [CR] + marrow CR [mCR] + partial remission [PR]) and median response duration was 21.4 months in 12 patients with mIDH1 R/R
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