Novel Therapies in Myeloproliferative Neoplasms: Beyond JAK Inhibitor Monotherapy.
| Autor: | Lee SS; Department of Internal Medicine, The University of Texas School of Health Sciences at Houston, Houston, TX, USA., Verstovsek S; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Pemmaraju N; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. |
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| Jazyk: | angličtina |
| Zdroj: | Journal of immunotherapy and precision oncology [J Immunother Precis Oncol] 2021 Jun 29; Vol. 4 (3), pp. 117-128. Date of Electronic Publication: 2021 Jun 29 (Print Publication: 2021). |
| DOI: | 10.36401/JIPO-20-35 |
| Abstrakt: | 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. Competing Interests: 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. (© Innovative Healthcare Institute 2021.) |
| Databáze: | MEDLINE |
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