Ruxolitinib for the treatment of primary myelofibrosis.

PURPOSE: The pharmacology, pharmacokinetics, pharmacogenomics, clinical efficacy, and safety profile of ruxolitinib for the treatment of primary myelofibrosis are reviewed.
SUMMARY: Ruxolitinib, an oral tyrosine kinase inhibitor that targets the Janus-associated kinases (JAKs) 1 and 2, has been recently approved for the treatment of patients with intermediate- or high-risk myelofibrosis. Unlike previous treatment options for patients with myelofibrosis, ruxolitinib offers a targeted therapy option for these patients who often suffer with severe and debilitating symptoms associated with the disease process. After oral administration, ruxolitinib is rapidly absorbed and can be given without regard to meals. Ruxolitinib is primarily metabolized by the cytochrome P-450 (CYP) 3A4 isoenzyme system; therefore, if concomitant use with a strong CYP3A4 inhibitor is unavoidable, an initial dosage reduction is warranted. Two Phase III randomized trials comparing ruxolitinib to either placebo or best available therapy found a rapid and sustained response in the reduction of spleen size and improvements in constitutional symptoms and quality of life, with one study demonstrating an improvement in overall survival. The most commonly reported serious adverse effects of ruxolitinib are anemia and thrombocytopenia. Ruxolitinib is administered as an oral tablet given twice daily, with the initial starting dosage based on the baseline platelet count. Dosage reductions are based on the development of thrombocytopenia.
CONCLUSION: By directly targeting both JAK1 and JAK2 through small-molecule inhibition, ruxolitinib elicits a reduction in splenomegaly and disease-related symptoms in patients with intermediate- or high-risk myelofibrosis while maintaining an acceptable toxicity profile and a low treatment-discontinuation rate.