Novel Therapies in Myeloproliferative Neoplasms (MPN): Beyond JAK Inhibitors
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.
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.
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.
KeywordsRuxolitinib Myeloproliferative neoplasms Novel therapies JAK inhibitors Novel drugs
This research is supported in part by the M. D. Anderson Cancer Center Support Grant P30 CA016672.
Compliance with Ethical Standards
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.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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