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Therapy with the histone deacetylase inhibitor pracinostat for patients with myelofibrosis
Alfonso Quintás-Cardama1, Hagop Kantarjian, Zeev Estrov
1Department of Leukemia, MD Anderson Cancer Center, Houston, TX 77030, USA. aquintas@mdanderson.org
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.
Insights
Pracinostat showed modest activity in myelofibrosis (MF) patients, with some experiencing spleen size reduction and anemia improvement. However, fatigue was common, and many discontinued treatment due to limited efficacy.
Area of Science:
- Oncology
- Hematology
- Pharmacology
Background:
- Myelofibrosis (MF) is a bone marrow cancer.
- Mutant JAK2(V617F) protein plays a role in MF pathogenesis.
- JAK2(V617F) influences gene transcription via histone modification.
Purpose of the Study:
- To evaluate the efficacy and tolerability of pracinostat in intermediate or high-risk MF patients.
- To assess clinical benefit, including spleen size reduction and anemia response.
Main Methods:
- A phase II study was conducted.
- 22 patients with intermediate or high-risk MF received pracinostat (60 mg every other day for three weeks per month).
- Outcomes included clinical benefit, splenomegaly reduction, anemia response, and adverse events.
Main Results:
- Eight patients (36%) experienced clinical benefit.
- Six patients (27%) showed reduced splenomegaly.
- Two patients (9%) achieved clinical improvement, with anemia response in both.
- Fatigue was the most frequent side effect (91%).
- Grade 3-4 neutropenia and thrombocytopenia occurred in 13% and 21% of patients, respectively.
Conclusions:
- Pracinostat at the tested dose is reasonably tolerated in MF patients.
- The drug demonstrated modest activity in this patient population.
- Lack of efficacy led to treatment discontinuation in most patients.
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