Abstract
ABSTRACT Introduction Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterized by bone marrow fibrosis, cytopenias, and organomegaly. Four JAK inhibitors are US-FDA approved for treatment of MF. While these drugs reduce symptom burden and spleen size to varying degrees, they do not affect the natural disease course or decrease the risk of leukemic transformation. Therefore, there is a strong need for newer therapies to further advance the field and improve the outcomes of MF. In this review, we cover novel therapies for MF currently in early stages of development. Areas covered We present the latest data from early phase clinical trials in MF using drugs with diverse therapeutic mechanisms, including novel JAK-STAT pathway inhibitors, epigenetic therapies, antifibrotic agents, and immunotherapeutic strategies. Additionally, we cover drugs targeted toward anemia improvement in MF. Expert opinion Numerous agents representing diverse drug classes are in clinical development for MF. While deeper and durable improvements in splenomegaly, symptoms, and anemia are the main clinical objectives, a number of putative biomarkers are being assessed as measures of potential ‘disease modification.’ Although JAK inhibitor monotherapy represents the current standard, it is hoped that JAK inhibitor-based rational combinations and driver mutation-specific therapies will soon usher in a new era.
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