A phase 2 study of pracinostat combined with ruxolitinib in patients with myelofibrosis.
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| Abstract |
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.
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| Authors | Prithviraj Bose, Mahesh Swaminathan, Naveen Pemmaraju, Alessandra Ferrajoli, Elias J Jabbour, Naval G Daver, Courtney D DiNardo, Yesid Alvarado, Musa Yilmaz, Julie Huynh-Lu, Wei Qiao, Xuemei Wang, Aurelio Matamoros, Lingsha Zhou, Sherry Pierce, Kurt D Schroeder, Hagop M Kantarjian, Srdan Verstovsek |
| Journal | Leukemia & lymphoma (Leuk Lymphoma) Vol. 60 Issue 7 Pg. 1767-1774 (07 2019) ISSN: 1029-2403 [Electronic] United States |
| PMID | 30632841 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't) |
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