Therapy with the histone deacetylase inhibitor pracinostat for patients with myelofibrosis

Abstract

Approximately half of the patients with myelofibrosis (MF) carry mutant JAK2(V617F) proteins. JAK2(V617F) has been recently shown to translocate to the nucleus and modify specific histones, thus regulating transcription. We report on a phase II study testing the activity and tolerability of the histone deacetylase inhibitor pracinostat given at 60 mg every other day for three weeks per month in 22 patients with intermediate or high risk MF. Eight (36%) patients experienced clinical benefit, with 6 (27%) experiencing reductions in splenomegaly (median 3 cm, range 1-4 cm). According to International Working Group criteria, 2 (9%) patients had clinical improvement (anemia response in both cases). The most frequent side effect associated to pracinostat therapy was fatigue, which occurred in 20 (91%) patients (grade 2 in 3 patients). Grade 3-4 neutropenia, anemia, and thrombocytopenia occurred in 13%, 0%, and 21%, respectively. Twenty-one patients permanently discontinued pracinostat, mainly due to lack of efficacy. In conclusion, pracinostat at the dose tested is reasonably tolerated and has modest activity in patients with MF.

Conflict of interest statement

Conflict of interest: AQ-C and SV have received research funding from SBIO. All other authors have no conflict of interest.

Copyright © 2012 Elsevier Ltd. All rights reserved.

Figures

Figure 1

Dynamics of splenomegaly reduction during pracinostat therapy for all patients with splenomegaly (n=21) and for those that responded to pracinostat therapy (n=6).

Figure 2

Dynamics of JAK2V617F allele burden during pracinostat therapy (n=18)