Second-line myelofibrosis treatment – the potential of JAK2 inhibitor NS-018

Srdan Verstovsek, MD, PhD, from the University of Texas MD Anderson Cancer Center, Houston, TX, discusses the potential of second-line treatment with the JAK inhibitor NS-018 in myelofibrosis at the American Society of Hematology (ASH) Congress 2016 in San Diego, CA. The underlying biological abnormality in patients with the myeloproliferative neoplasm myelofibrosis is a hyperactive intracellular JAK-STAT signaling pathway. NS-018 is a JAK inhibitor, a class of drugs which is known to result in patient benefit, with a significant reduction in the size of the spleen observed, which is enlarged in the majority of myelofibrosis patients, as well as a significant improvement in quality of life. Dr Verstovsek explains that ruxolitinib is approved as a frontline therapy for patients with myelofibrosis, and that the current study is in myelofibrosis patients refractory, resistant or intolerant to ruxolitinib. The Phase I/II second-line study (NCT01423851) of a JAK2 inhibitor after failure of ruxolitinib treatment treated 29 patients. Dr Verstovsek explains that around 12% of patients achieved significant symptomatic reduction, judged by MRI in this study to assess the spleen size. In addition, around one-third of patients achieved significant improvement in quality of life. Regarding the safety profile, no significant suppression of blood cell count, liver toxicity, neurological toxicity or other significant toxicity were seen. He concludes that NS-018 may be useful as a new drug in a second-line setting for myelofibrosis treatment, with potential for combination treatment strategies.

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