a Department of Leukemia , University of Texas MD Anderson Cancer Center , Houston , TX , USA.
b Department of Biostatistics , University of Texas MD Anderson Cancer Center , Houston , TX , USA.
Leuk Lymphoma. 2019 Jul;60(7):1767-1774. doi: 10.1080/10428194.2018.1543876. Epub 2019 Jan 11.
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.
虽然芦可替尼可改善晚期骨髓纤维化患者的症状和脾肿大，但该药物是否真正具有疾病修饰作用尚不清楚。组蛋白去乙酰化酶抑制剂（HDACi）通过干扰伴侣功能下调 JAK2。帕司他司坦是一种泛 HDACi，在骨髓纤维化中具有适度的单药活性。我们在一家机构进行了一项单臂、2 期、研究者发起的临床试验，评估了芦可替尼联合帕司他司坦（在芦可替尼治疗 12 周后开始）在 25 例骨髓纤维化患者中的疗效，其中 20 例患者接受了两种药物治疗。16 名（80%）患者有客观缓解（均为“临床改善”）。脾脏反应（触诊）率为 74%，症状反应率为 80%。大多数反应发生在开始使用帕司他司坦之前。3 名患者的骨髓纤维化有改善，1 名患者在研究治疗两年后出现近乎完全的分子缓解。所有患者均停用了帕司他司坦，目前已停止研究。帕司他司坦中断和剂量减少很常见，通常是由于贫血恶化。这些发现不支持继续开发帕司他司坦治疗骨髓纤维化。
