JAK Inhibitors in the Treatment of Myelofibrosis

Abstract: Myelofibrosis (MF) is a myeloproliferative neoplasm driven by constitutive activation of the JAK/STAT pathway, resulting in clonal hematopoiesis, fibrotic replacement of the bone marrow, extramedullary […]

How Early Intervention Impacts Long-Term Survival in Myelofibrosis

H&O  What are the signs and symptoms indicating that a patient with myelofibrosis requires treatment?  SV  According to standard practice, there are typically 3 indications for […]

Hem/Onc News

Entrectinib Approved for NTRK Fusion–Positive Solid Tumors and ROS1-Rearranged Non–Small Cell Lung Cancer On August 15, the US Food and Drug Administration (FDA) granted approval to […]

Proactive Steps to Optimize the Management of Polycythemia Vera and Myelofibrosis

  H&O  What are the management goals for polycythemia vera? RM  The first goal is to control hematocrit levels and avoid erythrocytosis to decrease the likelihood […]

Myelofibrosis: Clinicopathologic Features, Prognosis, and Management 

  Abstract: Myelofibrosis is one of the BCR-ABL–negative clonal disorders that collectively are known as myeloproliferative neoplasms (MPNs). It is caused by the proliferation of clonal […]

Polycythemia Vera: From New, Modified Diagnostic Criteria to New Therapeutic Approaches

  Abstract: Polycythemia vera (PV) is a Philadelphia chromosome–negative chronic myeloproliferative neoplasm that is associated with a Janus kinase 2 (JAK2) mutation in most cases. The […]

The New NCCN Guidelines for the Management of Myelofibrosis

H&O  What is myelofibrosis? RM  Myelofibrosis is a myeloproliferative neoplasm, a type of chronic leukemia. Myelofibrosis can evolve from an antecedent polycythemia vera or essential thrombocythemia, […]

When to Initiate Treatment in Myelofibrosis

H&O  What are the characteristics of myelofibrosis? CH The cardinal features of the blood cancer myelofibrosis are splenomegaly, fibrosis in the marrow, and either myeloid proliferation […]

Preclinical and Clinical Activity of ATP Mimetic JAK2 Inhibitors

Abstract: The discovery of a common Janus kinase 2 (JAK2) point mutation, JAK2V617F, in myeloproliferative neoplasms has generated enormous interest in the development and therapeutic use of small molecule JAK2 inhibitor–targeted therapy in these diseases. A handful of compounds are currently in clinical development in primary myelofibrosis or post-polycythemia vera (PV)/essential thrombocythemia (ET) myelofibrosis. To date, clinical benefit has been demonstrated in terms of reduction of splenomegaly, improvement in constitutional symptoms, and control of leukocytosis. Some of the drugs have also been evaluated in PV and ET, with demonstrated activity against erythrocytosis, thrombocytosis, pruritus, and splenomegaly. However, drug effect on bone marrow fibrosis or JAK2 allele burden has been modest so far. Regardless, it is important to keep in mind that current anti-JAK2 treatment trials constitute only the beginning of many upcoming similar clinical trials, and that it is premature to make generalizations or any form of comparative conclusions regarding drug activity or toxicity.