title: Therapy for myeloproliferative neoplasms: when, which agent, and how?
abstract: Myeloproliferative neoplasms, including polycythemia vera (PV), essential thrombocythemia, and myelofibrosis (MF) (both primary and secondary), are recognized for their burdensome symptom profiles, life-threatening complications, and risk of progression to acute leukemia. Recent advancements in our ability to diagnose and prognosticate these clonal malignancies have paralleled the development of MPN-targeted therapies that have had a significant impact on disease burden and quality of life. Ruxolitinib has shown success in alleviating the symptomatic burden, reducing splenomegaly and improving quality of life in patients with MF. The role and clinical expectations of JAK2 inhibition continues to expand to a variety of investigational arenas. Clinical trials for patients with MF focus on new JAK inhibitors with potentially less myelosuppression (pacritinib) or even activity for anemia (momelotinib). Further efforts focus on combination trials (including a JAK inhibitor base) or targeting new pathways (ie, telomerase). Similarly, therapy for PV continues to evolve with phase 3 trials investigating optimal frontline therapy (hydroxyurea or IFN) and second-line therapy for hydroxyurea-refractory or intolerant PV with JAK inhibitors. In this chapter, we review the evolving data and role of JAK inhibition (alone or in combination) in the management of patients with MPNs.
authors.affiliation: Division of Hospital Internal Medicine and.
authors.forename: Holly L
authors.initials: HL
authors.lastname: Geyer
authors.affiliation: Division of Hematology and Medical Oncology, Mayo Clinic, Scottsdale, AZ.
authors.forename: Ruben A
authors.initials: RA
authors.lastname: Mesa
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009196:Myeloproliferative Disorders / Q000188:drug therapy* / Q000201:enzymology; D017410:Practice Guidelines as Topic; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C507924:JAK2 protein, human; D053614:Janus Kinase 2