Myelofibrosis (MF) is a
hematologic malignancy characterized by abnormal proliferation of myeloid cells and the release of pro-inflammatory
cytokines, leading to progressive bone marrow dysfunction. The introduction of
ruxolitinib just over a decade ago marked a significant advancement in MF
therapy, with
JAK inhibitors now being the first-line treatment for reducing spleen size and managing symptoms. However, early
JAK inhibitors (
ruxolitinib and
fedratinib) are often associated with
cytopenias, particularly
thrombocytopenia and
anemia, which limit their tolerability. To address these complications,
pacritinib has been developed and recently approved for patients with
thrombocytopenia, while
momelotinib is in development for those with
anemia. Although
JAK inhibitors have significantly improved the quality of life of MF patients, they have not demonstrated the ability to reduce leukemic transformation and their impact on survival is debated. Numerous drugs are currently being developed and investigated in clinical trials, both as standalone
therapy and in combination with
JAK inhibitors, with promising results enhancing the benefits of
JAK inhibitors. In the near future, MF treatment strategies will involve selecting the most suitable
JAK inhibitor based on individual patient characteristics and prior
therapy. Ongoing and future clinical trials are crucial for advancing the field and expanding therapeutic options for MF patients.