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Fedratinib for the treatment of myelofibrosis: a critical appraisal of clinical trial and "real-world" data.
Blood Cancer J
January 2025
School of Medicine, Faculty of Medicine and Health Sciences, Tel Aviv University, Tel Aviv, Israel.
Fedratinib is a predominantly JAK2 inhibitor that has shown efficacy in untreated and ruxolitinib-exposed patients with myelofibrosis (MF). Based on randomized clinical trial data, it is approved for use in patients with International Prognostic Scoring System (IPSS) or Dynamic International Prognostic Scoring System (DIPSS) intermediate-2 or high-risk disease and is distinguished from ruxolitinib in that it can be administered without dose reduction in patients with thrombocytopenia, to a platelet count above 50,000/µL. In these trials, fedratinib achieved significant spleen volume reduction in ~30-45% of patients and improvement in total symptom scores in 35-40% with good tolerability.
View Article and Find Full Text PDFBackground: Hemophagocytic lymphohistiocytosis (HLH) is a rare complication of multiple myeloma (MM), with limited data available on its incidence, clinical presentation, and treatment. The underlying mechanisms linking MM and HLH remain unclear, including the potential role of MM treatment agents in triggering HLH.
Methods: This case report presents a patient with MM who developed HLH while on lenalidomide maintenance therapy.
Inhibition of Mitochondrial Succinate Dehydrogenase with Dimethyl Malonate Promotes M2 Macrophage Polarization by Enhancing STAT6 Activation.
Inflammation
January 2025
Department of Respiratory Medicine, Shenzhen Longhua District Central Hospital, Shenzhen, 518110, China.
Macrophages exhibit diverse phenotypes depending on environment status, which contribute to physiological and pathological processes of immunological diseases, including sepsis, asthma, multiple sclerosis and colitis. The alternative activation of macrophages is tightly regulated to avoid excessive activation and damage of tissues and organs. Certain works characterized that succinate dehydrogenase (SDH) altered function of macrophages and promoted inflammatory response in M1 macrophages via mitochondrial reactive oxygen species (ROS).
View Article and Find Full Text PDFPARADIGM-PV: a randomized, multicenter phase 4 study to assess the efficacy and safety of ropeginterferon alfa-2b in patients with low- or high-risk polycythemia vera.
Ann Hematol
January 2025
Department of Medicine, School of Clinical Medicine, LKS Faculty of Medicine, the University of Hong Kong, Hong Kong, China.
Polycythemia vera (PV) is characterized by clonal hematopoietic stem or progenitor cells with constitutively active somatic mutation(s) in the Janus kinase 2 gene. Phlebotomy (Phl) and aspirin are often used alone for low-risk PV patients. However, data from the Low-PV study demonstrated that Phl and aspirin may not be adequate for patients.
View Article and Find Full Text PDFAdvances in Myelofibrosis Management: New Janus Kinase Inhibitors Beyond Ruxolitinib.
J Adv Pract Oncol
May 2024
Levine Cancer Institute, Atrium Health, Charlotte, North Carolina.
Myelofibrosis is a myeloproliferative neoplasm characterized by the buildup of fibrous scar tissue in the bone marrow occurring secondary to the secretion of inflammatory cytokines, leading to cytopenias, dysfunctional hematopoiesis, and constitutional symptoms. One of the pathologic mechanisms that underlies myelofibrosis is aberrant activation of the Janus kinase (JAK)-STAT pathway. Targeting the JAK-STAT pathway via JAK inhibition can lead to significant improvements in spleen volume reduction and symptom improvement in intermediate- and high-risk myelofibrosis.
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