Abstracts Clinical Lymphoma, Myeloma & Leukemia September 2023 S378 Bosler MD2, Halle Moore MD3, Jame Abraham MD3, Jessica Geiger MD4, Aaron T. Gerds MD1, Anjali S. Advani MD1, Sudipto Mukherjee MD, MPH1, Jaroslaw P. Maciejewski MD, PhD1,5, Brian Bolwell MD1, Hetty Carraway MD, MBA1, Bhumika J. Patel MD6, Abhay Singh MD, MPH1 1Leukemia Program, Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, USA. 2Laboratory Medicine, Cleveland Clinic, Cleveland, USA. 3Breast Program, Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, USA. 4Head and Neck Program, Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, USA. 5Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, USA. 6Hematology Oncology Program, Prisma Health, Greenville, USA Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) is a precursor state to hematological malignancies and is associated with increased risk of cardiovascular disease (CVD) and increased all-cause mortality. CHIP can therefore contribute to longterm morbidity and mortality in cancer survivors. There is currently paucity of data about the demographics, management and clinical outcomes of CHIP patients seen in the survivorship setting. Our CHIP clinic model addresses this issue following cancer survivors for potential long-term CHIP related issues. Methods: The patients in Breast (BC), Head and Neck (HNC) cancer survivorship at Cleveland Clinic between 2020 and 2023 are included in our prospective study. Patients are being followed at our clinic with annual next generation sequencing (NGS) and complete blood count. Patient data encompassing demographics, cancer type and stage, chemo-radiotherapy exposure, autoimmune history, cardiac risk factors, medications, and clinical outcomes are collected. Fischer’s exact test and ANOVA were employed for data analysis. Results: A total of 168 patients (117 BC, 51 HNC) were referred to the CHIP clinic between 2020 and 2023. Among them, 158 patient samples underwent NGS testing. CHIP was detected in 21 patients (13%), with 6 individuals exhibiting pathogenic variants of uncertain significance (PG VUS). Two patients developed CHIP mutations in the second year of follow-up. DNMT3A (n=11), PPM1D (6), TET2 (6), JAK2(2), TP53 (2), and several potentially germline variants were identified in our CHIP patients, with referrals to medical geneticists as deemed necessary. Six pts had thrombocytopenia (TP), 3 with PPM1D CHIP. TP was more common in CHIP (OR 11, P=0.0356) and PPM1D (OR 29, P=0.0016). All the CHIP patients were established under the care of expert hematologists and preventive cardiologists (PC). Seven CHIP patients seen by PC had adjustments in cardiovascular medications. Conclusions: This ongoing prospective cohort study is one of the largest to report characteristics and clinical outcomes of patients referred to a CHIP clinic with anticipated further expansion. Collaborative efforts between hematologists and cardiologists have led to improved cardiac management in numerous patients. The study results will contribute to the development of better risk predictors for therapyrelated myeloid neoplasms (tMN) and identification of targeted mechanisms to prevent fatal complications. Keywords: MDS, CHIP, clonal hematopoiesis of indeterminate potential Myeloproliferative Neoplasms MPN-056 Fedratinib May Be the First Choice for Patients Affected by Myelofibrosis and Concurrent Lymphoproliferative Disorder or Developed After Another JAKi Therapy Andrea Duminuco MD, Antonella Nardo MD, Giuseppe Palumbo MD A.O.U. Policlinico “G.Rodolico-San Marco”, Catania, Italy Context: The simultaneous presence of myeloproliferative diseases, specifically myelofibrosis (MF) and lymphoproliferative disorders (LPD), has been reported. The first-in-class JAKi ruxolitinib (RUX) can control the disease, splenomegaly, and systemic symptoms. The inhibition of the JAK-STAT pathway leads to a state of immunosuppression, with an increased risk of infections or growth of pre-existing lymphoid clones, resulting in LPD. Considering the studies currently available evaluating the correlation between myeloproliferative neoplasms (MPN) and LPD, we note different results. In the cohort of Pemmaraju and colleagues, only 9 (0.56%) MF patients developed an LPD, of which 6 were previously treated with RUX. In the European group, 4 (5.8%) of 69 patients who received JAKi treatment experienced aggressive B-cell non-Hodgkin lymphomas, reporting an increased risk compared with patients treated with other drugs (2–0.36%). Aims: In our experience, we report the cases of 2 patients affected by LPD arising during treatment with RUX for MF and for whom we decided to switch therapy to fedratinib (FED) with a subsequent spontaneous disappearance of LPD. Case Presentation: The first is a case of a 65-year-old woman affected by JAK2 mutated PPV-MF. After about 12 months of treatment with RUX, we found 2 new cutaneous lesions in the scapular region, diagnostic for cutaneous marginal zone lymphoma (MZL). Considering the relationship between LPD and RUX treatment, we discontinued RUX administration. We started therapy with FED at the standard dose of 400 mg daily, with the progressive disappearance of the lesions in about 2 months and reasonable control of the underlying MF. The second case is a man affected by CALR-mutated PET-MF who began RUX treatment. During the follow-up, after 5 months of RUX, lymphocyte count had increased, with immunophenotype diagnostic for chronic lymphocytic leukemia (CLL). After the LPD diagnosis, we decided to withdraw RUX and treat the patient with FED without accessory treatment for the indolent CLL. Immediately after the RUX discontinuation, we witnessed a progressive decrease in lymphocyte count, reaching values around the upper threshold limit. Conclusion: Our limited series suggests carefully evaluating patients affected by MPN and treated with JAKi, with the key role of FED in these cases instead of RUX. Keywords: lymphoproliferative disorders, myelofibrosis, ruxolitinib, fedratinib, JAK/STAT pathway, case, myeloproliferative neoplasm
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