JAK Inhibitors for the Treatment of Haemato-Oncological Diseases

The constitutive activation of the JAK-STAT signalling pathway is a pathogenetic hallmark of myeloproliferative neoplasms, in particular of primary myelofibrosis, polycythaemia vera and essential thrombocythaemia. The introduction of orally available JAK inhibitors into clinics yielded a major progress for the pharmacological treatment of myelofibrosis and polycythaemia vera, although they have not been able to cure these conditions. The primary goal is to improve the quality of life in the predominantly elderly patients by controlling the constitutional symptoms caused by the disease, to reduce existing splenomegaly and to prevent subsequent thromboembolic complications. Moreover, the therapeutic administration of JAK inhibitors to patients with myelofibrosis may decelerate the course of their disease and prolong their overall survival. So far, Ruxolitinib is the only JAK inhibitor approved in Europe. It targets both isoforms JAK1 and JAK2 and has antiinflammatory as well as antiproliferative potential. Consequently, this inhibitor also proves effective in treating graft-versus-host disease occurring after allogeneic haematopoietic stem cell transplantation. Next in line, Fedratinib, Pacritinib and Momelatinib are three promising JAK inhibitors with slightly different activity profiles, which are currently undergoing clinical phase III testing. They prove effective even in patients with prior ineffective or intolerable exposure to Ruxolitinib. Thus, a continuous improvement of the respective treatment strategies can be expected.