TY - JOUR
T1 - Therapy with the histone deacetylase inhibitor pracinostat for patients with myelofibrosis
AU - Quintás-Cardama, Alfonso
AU - Kantarjian, Hagop
AU - Estrov, Zeev
AU - Borthakur, Gautam
AU - Cortes, Jorge
AU - Verstovsek, Srdan
N1 - Funding Information:
Conflict of interest . AQ-C and SV have received research funding from SBIO. All other authors have no conflict of interest.
PY - 2012/9
Y1 - 2012/9
N2 - 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 60mg 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 3cm, range 1-4cm). 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.
AB - 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 60mg 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 3cm, range 1-4cm). 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.
KW - Histone deacetylase inhibitor
KW - JAK2
KW - Myelofibrosis
KW - Pracinostat
KW - SB939
UR - http://www.scopus.com/inward/record.url?scp=84864008019&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84864008019&partnerID=8YFLogxK
U2 - 10.1016/j.leukres.2012.03.003
DO - 10.1016/j.leukres.2012.03.003
M3 - Article
C2 - 22475363
AN - SCOPUS:84864008019
SN - 0145-2126
VL - 36
SP - 1124
EP - 1127
JO - Leukemia Research
JF - Leukemia Research
IS - 9
ER -