TY - JOUR
T1 - A phase 2 study of pracinostat combined with ruxolitinib in patients with myelofibrosis
AU - Bose, Prithviraj
AU - Swaminathan, Mahesh
AU - Pemmaraju, Naveen
AU - Ferrajoli, Alessandra
AU - Jabbour, Elias J.
AU - Daver, Naval G.
AU - DiNardo, Courtney D.
AU - Alvarado, Yesid
AU - Yilmaz, Musa
AU - Huynh-Lu, Julie
AU - Qiao, Wei
AU - Wang, Xuemei
AU - Matamoros, Aurelio
AU - Zhou, Lingsha
AU - Pierce, Sherry
AU - Schroeder, Kurt D.
AU - Kantarjian, Hagop M.
AU - Verstovsek, Srdan
N1 - Funding Information:
This work was supported in part by MEI Pharma, who provided pracinostat and financial support for the study, as well as the MD Anderson Cancer Center Support Grant P30 CA016672 from the National Cancer Institute (National Institutes of Health).
Publisher Copyright:
© 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2019/6/7
Y1 - 2019/6/7
N2 - Although ruxolitinib improves symptoms and splenomegaly in patients with advanced myelofibrosis, whether this agent is truly disease-modifying remains unclear. Histone deacetylase inhibitors (HDACi) downregulate JAK2 via interference with chaperone function. Pracinostat, a pan-HDACi, has modest single-agent activity in myelofibrosis. We conducted a single-institution, phase 2, investigator-initiated trial of ruxolitinib plus pracinostat (begun after 12 weeks of ruxolitinib) in 25 patients with myelofibrosis, of whom 20 received both agents. Sixteen (80%) patients had objective responses (all ‘clinical improvement’). The rate of spleen response (by palpation) was 74%, and that of symptom response 80%. Most responses occurred prior to pracinostat initiation. Three patients experienced improvement in bone marrow fibrosis, and one a near-complete molecular response after two years on study treatment. All patients discontinued pracinostat and are currently off-study. Pracinostat interruptions and dose reductions were frequent, often due to worsening anemia. These findings do not support continued development of pracinostat in myelofibrosis.
AB - Although ruxolitinib improves symptoms and splenomegaly in patients with advanced myelofibrosis, whether this agent is truly disease-modifying remains unclear. Histone deacetylase inhibitors (HDACi) downregulate JAK2 via interference with chaperone function. Pracinostat, a pan-HDACi, has modest single-agent activity in myelofibrosis. We conducted a single-institution, phase 2, investigator-initiated trial of ruxolitinib plus pracinostat (begun after 12 weeks of ruxolitinib) in 25 patients with myelofibrosis, of whom 20 received both agents. Sixteen (80%) patients had objective responses (all ‘clinical improvement’). The rate of spleen response (by palpation) was 74%, and that of symptom response 80%. Most responses occurred prior to pracinostat initiation. Three patients experienced improvement in bone marrow fibrosis, and one a near-complete molecular response after two years on study treatment. All patients discontinued pracinostat and are currently off-study. Pracinostat interruptions and dose reductions were frequent, often due to worsening anemia. These findings do not support continued development of pracinostat in myelofibrosis.
KW - HDAC inhibitors
KW - JAK2 inhibitors
KW - Myelofibrosis
KW - rational combinations
KW - targeted therapies
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U2 - 10.1080/10428194.2018.1543876
DO - 10.1080/10428194.2018.1543876
M3 - Article
C2 - 30632841
AN - SCOPUS:85060037678
SN - 1042-8194
VL - 60
SP - 1767
EP - 1774
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 7
ER -