Author(s): Komrokji RS, Verstovsek S, Padron E, List AF
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Abstract BACKGROUND: Myelofibrosis (MF) is a rare and serious hematologic malignancy classified as a Philadelphia chromosome-negative myeloproliferative neoplasm (MPN). The disease is more common in males and in older individuals. Of the MPNs, MF presents with the most severe morbidity and greatest mortality. Although the cause of MF is unknown, it is thought to occur from acquired mutations that target the hematopoietic stem cell. METHODS: We reviewed the current literature pertaining to the pathophysiology, clinical presentation, diagnosis, risk stratification, and treatment of MF. The strengths and limitations of present treatment options as well as the emerging clinical experience with Janus kinase 2 (JAK2) inhibitors are explored. RESULTS: Diagnosis is often one of exclusion and is facilitated using the World Health Organization or International Working Group for Myelofibrosis Research and Treatment criteria, depending on whether primary or secondary MF is suspected. Treatment is complicated by a lack of disease familiarity of general practitioners and the advanced age of presenting patients. Although allogeneic stem cell transplant offers a potential cure, most treatments for this condition are limited to symptomatic management, with little to no effect on survival. Appropriate patient assessment and risk stratification are essential for predicting outcomes and allowing treating physicians to tailor therapy accordingly. CONCLUSIONS: Significant advances have been made in understanding the pathophysiology of MF, leading to novel therapeutic approaches. The discovery of the JAK2 mutation and the development of JAK2 inhibitors provide clinicians with a new effective treatment option. Ruxolitinib is the first JAK1/2 inhibitor approved by the Food and Drug Administration (FDA) for the treatment of patients with intermediate- or high-risk MF. In clinical studies, ruxolitinib produced a significantly greater reduction in spleen size and improved quality of life compared with placebo or best available therapy. Several future therapies, including combination therapies with ruxolitinib, are currently under investigation.
This article was published in Cancer Control
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