New drugs in myelofibrosis: Critical assessment of additional value to monotherapy with JAK inhibitors

Abstract

Among the JAK2 mutation-prevalent myeloproliferative neoplasms, myelofibrosis (MF) is prognostically the worst with median survival estimates ranging from less than 2 years to over 10 years, depending on the presence or absence of specific genetic and clinical risk factors. 1 Moreover, quality of life (QoL) in MF is severely compromised by progressive anemia, splenomegaly, and constitutional symptoms. At present, the only treatment modality in MF with the potential to cure the disease or prolong survival is allogeneic hematopoietic stem cell transplant. 2 On the other hand, current drug therapy, including that with JAK inhibitors (JAKi), has been shown to be effective in improving QoL by way of alleviating constitutional symptoms, reducing spleen size, reversing cachexia, and, in some instances, resulting in resolution of red cell transfusion need. 3 Ruxolitinib was the first JAKi to receive the United States Food and Drug Administration (FDA) approval in 2011, followed by approval of three additional JAKi, namely, fedratinib (2019), pacritinib (2022), and momelotinib (2023), the latter two in the context of thrombocytopenia (platelet count <50 Â 10 9 /L), and anemia, respectively. 4 All four FDA-approved JAKi alleviate