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Novel Therapies in Myeloproliferative Neoplasms (MPN): Beyond JAK Inhibitors

Current Hematologic Malignancy Reports volume 14, pages 460–468 (2019)Cite this article

Abstract

Purpose of Review

With increased understanding of the pathobiology of myeloproliferative neoplasms (MPNs), multiple new agents are now being investigated. We aim to cover some of the current treatment options for MPNs and discuss new agents in development.

Recent Findings

The introduction of ruxolitinib improved the treatment of many patients with intermediate and higher risk myelofibrosis. However, ruxolitinib monotherapy does not benefit all patients, and not all patients can receive this therapy due to limiting cytopenias. The unraveling of new molecular abnormalities and cellular pathways led to the development of several novel targeted agents that are currently under investigation in clinical trials. These agents have different mechanisms of action and are being used either alone or in combination with ruxolitinib.

Summary

Novel targets include inhibition of apoptosis, the tumor microenvironment, telomerase enzyme action, immunotherapy, and fibrosis with associated cytokines. We comprehensively review and summarize the available preclinical and clinical trials with novel agents for MPNs.

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Funding

This research is supported in part by the M. D. Anderson Cancer Center Support Grant P30 CA016672.

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Authors and Affiliations

  1. Department of Internal Medicine, The University of Texas School of Health Sciences at Houston, Houston, TX, USA

    Minas P. Economides

  2. Department of Leukemia, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA

    Srdan Verstovsek & Naveen Pemmaraju

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  1. Minas P. Economides
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  2. Srdan Verstovsek
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Correspondence to Naveen Pemmaraju.

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Conflict of Interest

Minas P. Economides declares no conflict of interest.

Srdan Verstovsek declares the following: Consulting/honorarium from Constellation, Pragmatist, Sierra, Incyte Corporation, Novartis, and Celgene. Research funding/clinical trials support from Incyte Corporation, Roche, NS Pharma, Celgene, Gilead, Promedior, CTI BioPharma Corp., Genentech, Blueprint Medicines Corp., and Novartis.

Naveen Pemmaraju declares the following: Consulting/honorarium from Celgene, Stemline, Incyte Corporation, Novartis, MustangBio, Roche Diagnostics, and LFB. Research funding/clinical trials support from Stemline, Novartis, Abbvie, Samus, Cellectis, Plexxikon, Daiichi-Sankyo, Affymetrix, and SagerStrong Foundation.

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This article is part of the Topical Collection on Myeloproliferative Neoplasms

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Economides, M.P., Verstovsek, S. & Pemmaraju, N. Novel Therapies in Myeloproliferative Neoplasms (MPN): Beyond JAK Inhibitors. Curr Hematol Malig Rep 14, 460–468 (2019). https://doi.org/10.1007/s11899-019-00538-4

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Keywords

  • Ruxolitinib
  • Myeloproliferative neoplasms
  • Novel therapies
  • JAK inhibitors
  • Novel drugs