Current treatments, practical management, and emerging investigational therapies for myelofibrosis

Myelofibrosis is a clonal myeloproliferative neoplasm characterized by bone marrow fibrosis, extramedullary hematopoiesis, splenomegaly, progressive cytopenias, and systemic symptoms, with risk of leukemic transformation. Advances in understanding its molecular pathogenesis, particularly JAK-STAT signaling, have reshaped treatment approaches, though allogeneic transplantation remains the only potential cure.

We review current diagnostic frameworks, prognostic models, and treatment strategies, including approved JAK inhibitors and emerging investigational therapies. Literature was identified through PubMed searches and relevant conference proceedings, with emphasis on pivotal clinical trials, novel targeted agents, and evolving management of cytopenias and advanced disease.

It is an exciting time in myelofibrosis research. Investigation into the molecular underpinnings of the disease and elucidation of many key pathways beyond JAK-STAT signaling have led to a profusion of new drug classes entering the clinic. The results of several, potentially paradigm-shifting key phase 3 trials are eagerly awaited. While JAK inhibitors remain the only approved agents, this could soon change. Equally, there is a major focus on next generation JAK inhibitors and mutant calreticulin antibodies. There is also increasing conversation around the need for novel endpoints, as the limitations of symptom assessment, in particular, become apparent and candidate biomarkers of disease modification emerge.