n-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide and Infections

Myelofibrosis (MF) is characterized by bone marrow fibrosis, abnormalities in peripheral counts, extramedullary hematopoiesis, splenomegaly and an increased risk of transformation to acute myeloid leukaemia. The disease course is often heterogeneous and management can range from observation alone through to allogeneic stem cell transplantation. As of 2017, the only approved medication for MF remains the JAK Inhibitor (JAKi), ruxolitinib (Novartis Pharmaceuticals, Basel, Switzerland; Incyte, Wilmington, Detroit, USA) although several others have reached advanced stages of clinical trials. Areas covered: In this review, we focus on the management of both common and uncommon side effects arising from the use of currently approved and clinical trial JAKi. Most of the discussion concerns ruxolitinib although we also cover both pacritinib (CTI BioPharma) and momelotinib (Gilead Sciences, Foster City, California) which have been in recent large, multinational phase III trials. The various approaches to management of JAKi-related side effects are discussed - with particular emphasis to anaemia, thrombocytopaenia and infection risk. Expert commentary: JAK inhibitors are effective in many individuals with MF and have revolutionized the current treatment paradigm. The side effect profile, in the most, is predictable and manageable with high degrees of clinical surveillance and dose modifications.

Topics: Anemia; Benzamides; Bridged-Ring Compounds; Clinical Trials as Topic; Disease Management; Humans; Infections; Janus Kinases; Nitriles; Primary Myelofibrosis; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines; Thrombocytopenia