TY - JOUR
T1 - Novel therapies in myeloproliferative neoplasms
T2 - Beyond JAK inhibitor monotherapy
AU - Lee, Sophia S.
AU - Verstovsek, Srdan
AU - Pemmaraju, Naveen
N1 - Publisher Copyright:
© Innovative Healthcare Institute.
PY - 2021/8
Y1 - 2021/8
N2 - 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.
AB - 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.
KW - JAK inhibitor
KW - MPN
KW - Myelofibrosis
KW - Myeloproliferative neoplasms
KW - Novel therapy
KW - Ruxolitinib
UR - http://www.scopus.com/inward/record.url?scp=85113768510&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85113768510&partnerID=8YFLogxK
U2 - 10.36401/JIPO-20-35
DO - 10.36401/JIPO-20-35
M3 - Review article
C2 - 35663101
AN - SCOPUS:85113768510
SN - 2666-2345
VL - 4
SP - 117
EP - 128
JO - Journal of Immunotherapy and Precision Oncology
JF - Journal of Immunotherapy and Precision Oncology
IS - 3
ER -