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Review
. 2021 Jun 29;4(3):117-128.
doi: 10.36401/JIPO-20-35. eCollection 2021 Aug.

Novel Therapies in Myeloproliferative Neoplasms: Beyond JAK Inhibitor Monotherapy

Sophia S Lee  1 , Srdan Verstovsek  2 , Naveen Pemmaraju  2
Affiliations
Review

Novel Therapies in Myeloproliferative Neoplasms: Beyond JAK Inhibitor Monotherapy

Sophia S Lee et al. J Immunother Precis Oncol. .

Abstract

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic disorders that consist classically of polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF). Janus kinase (JAK) inhibitors have become the standard of therapy in treating patients with intermediate- to higher-risk MF. However, JAK inhibitor (JAKi) treatment can be associated with development of resistance, suboptimal response, relapse, or treatment-related adverse effects. With no approved therapies beyond the JAKi class, the estimated median survival, post JAKi failure, is approximately two years or less; therefore, novel therapies are urgently needed in the MF field. In this review, we discuss ruxolitinib use in MPNs as well as causes of ruxolitinib failure or discontinuation. In addition, we review novel therapies being investigated alone or in combination with JAKi administration. We summarize concepts and mechanisms behind emerging novel therapies being studied for MPNs. This review of emerging novel therapies outlines several novel mechanisms of agents, including via promotion of apoptosis, alteration of the microenvironment, activation or inactivation of various pathways, targeting fibrosis, and telomerase inhibition.

Keywords: JAK inhibitor; MPN; myelofibrosis; myeloproliferative neoplasms; novel therapy; ruxolitinib.

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Conflict of interest statement

Conflict of Interest: Sophia S. Lee: None. Srdan Verstovsek: Research support for conduct of clinical studies from Incyte, Roche, NS Pharma, Celgene, Gilead, Promedior, CITI BioPharma Corp., Genentech, Blueprint Medicines Corp., Novartis, Sierra Oncology, Pharma Essentia, Astrazeneca, Ital Pharma, and Protagonist Therapeutics. Consulting fees from Constellation, Pragmatist, Sierra, Incyte, Novartis, and Celgene. Naveen Pemmaraju: Consulting/honorarium from Pacylex Pharmaceuticals, Incyte, Novartis, LFB Biotechnologies, Stemline, Celgene, AbbVie, MustangBio, Roche Diagnostics, Blueprint Medicines, and DAVA Oncology; research funding/clinical trials support from Affymetrix, SagerStrong Foundation, Novaris, Stemline, Samus, AbbVie, Cellectis, Daiichi Sankyo, and Plexxikon.

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