Givinostat: an emerging treatment for polycythemia vera.

Expert Opinion on Investigational Drugs
Helen T ChifotidesSrdan Verstovsek

Abstract

Polycythemia vera (PV), a Philadelphia chromosome-negative myeloproliferative neoplasm, is characterized by panmyelosis, pancytosis, and a JAK2 mutation. Patients are at increased risk of thrombohemorrhagic events, and progression to myelofibrosis or acute leukemia. Current treatments include aspirin, phlebotomy, and cytoreductive drugs (most commonly hydroxyurea). Givinostat is a potent, class I/II histone deacetylase (HDAC) inhibitor that is in phase I/II clinical trials in PV. Givinostat was well tolerated and yielded promising clinico-hematological responses. A phase III study of givinostat versus hydroxyurea in high-risk PV patients is planned. We present an overview of PV, current treatment guidelines, and the putative mechanism(s) of action of givinostat. We discuss the preclinical and clinical studies of givinostat in PV and briefly review approved and investigational competitor compounds. HDAC inhibitors have long been known to be active in PV, but chronic toxicities can be challenging. Givinostat, however, is active and well tolerated, and is entering a pivotal Phase III randomized trial. Givinostat offers the possibility of replacing hydroxyurea as the standard first-line cytoreductive choice for PV patients. This wo...Continue Reading

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Citations

Mar 2, 2021·Hematology/oncology Clinics of North America·Ashwin Kishtagari, Aaron T Gerds
Mar 25, 2021·Therapeutics and Clinical Risk Management·Giulia BenevoloValentina Giai
Apr 13, 2021·Journal of Biomedical Science·Kunal Nepali, Jing-Ping Liou
Apr 21, 2021·Current Hematologic Malignancy Reports·Brandi N Reeves, Joan D Beckman
May 30, 2021·Biomarker Research·Rory M Shallis, Nikolai A Podoltsev

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