Myelofibrosis (MF) is currently the myeloproliferative disorder with the most severe prognosis. A mutation of the JAK2 (V617F) enzyme is present in about 65 % of patients. Inhibition of JAK-kinases was therefore a proposed treatment for the disease. The purpose of this article is to give an updated overview about the recent developments in the therapy of MF with JAK-inhibitors.
Materials and methods
We did a research through the literature to identify the JAK 1/2 inhibitors which are already approved for treating MF or currently undergoing clinical trials. The most important clinical data concerning ruxolitinib, TG101348, SAR302503, CYT387, and SB1518 are described in more detail.
Most of the relevant data documented clinical benefits of JAK inhibitors, particularly in terms of reducing splenomegaly and constitutional symptoms. However, there might also be a trend for better overall survival. The efficacy of ruxolitinib has been demonstrated in two large Phase III trials. In September 2012, the European Medicines Agency (EMA) approved ruxolitinib for the treatment of patients with intermediate or high-risk MF. The other drugs discussed here are still investigated in Phase II or III studies.
There is emerging evidence that supports the use of JAK-inhibitors for MF in clinical practice, especially for patients with splenomegaly and constitutional symptoms. Nevertheless, possible side effects such as anemia and thrombopenia must be considered when prescribing these substances.