Komrokji Rami S, Seymour John F, Roberts Andrew W, Wadleigh Martha, To L Bik, Scherber Robyn, Turba Elyce, Dorr Andrew, Zhu Joy, Wang Lixia, Granston Tanya, Campbell Mary S, Mesa Ruben A
Moffitt Cancer Center, Tampa, FL;
Peter McCallum Cancer Center, Melbourne, Australia; Sir Peter MacCallum Department of Oncology.
Blood. 2015 Apr 23;125(17):2649-55. doi: 10.1182/blood-2013-02-484832. Epub 2015 Mar 11.
Pacritinib (SB1518) is a Janus kinase 2 (JAK2), JAK2(V617F), and Fms-like tyrosine kinase 3 inhibitor that does not inhibit JAK1. It demonstrated a favorable safety profile with promising efficacy in phase 1 studies in patients with primary and secondary myelofibrosis (MF). This multicenter phase 2 study further characterized the safety and efficacy of pacritinib in the treatment of patients with MF. Eligible patients had clinical splenomegaly poorly controlled with standard therapies or were newly diagnosed with intermediate- or high-risk Lille score. Patients with any degree of cytopenia were eligible. Thirty-five patients were enrolled. At entry, 40% had hemoglobin <10 g/dL and 43% had platelets <100 000× 10(9)/L. Up to week 24, 8 of 26 evaluable patients (31%) achieved a ≥35% decrease in spleen volume determined by magnetic resonance imaging and 14 of 33 (42%) attained a ≥50% reduction in spleen size by physical examination. Median MF symptom improvement was ≥50% for all symptoms except fatigue. Grade 1 or 2 diarrhea (69%) and nausea (49%) were the most common treatment-emergent adverse events. The study drug was discontinued in 9 patients (26%) due to adverse events (4 severe). Pacritinib is an active agent in patients with MF, offering a potential treatment option for patients with preexisting anemia and thrombocytopenia. This trial was registered at www.clinicaltrials.gov as #NCT00745550.
帕西替尼（SB1518）是一种不抑制JAK1的 Janus激酶2（JAK2）、JAK2（V617F）和Fms样酪氨酸激酶3抑制剂。在原发性和继发性骨髓纤维化（MF）患者的1期研究中，它显示出良好的安全性和有前景的疗效。这项多中心2期研究进一步明确了帕西替尼治疗MF患者的安全性和疗效。符合条件的患者临床脾肿大经标准治疗控制不佳，或新诊断为中高危里尔评分。任何程度血细胞减少的患者均符合条件。共纳入35例患者。入组时，40%的患者血红蛋白<10 g/dL，43%的患者血小板<100 000×10⁹/L。至第24周，26例可评估患者中有8例（31%）经磁共振成像测定脾脏体积减少≥35%，33例中有14例（42%）经体格检查脾脏大小缩小≥50%。除疲劳外，所有症状的MF症状改善中位数≥50%。1级或2级腹泻（69%）和恶心（49%）是最常见的治疗中出现的不良事件。9例患者（26%）因不良事件（4例严重）停用研究药物。帕西替尼对MF患者是一种有效药物，为已有贫血和血小板减少的患者提供了一种潜在的治疗选择。该试验在www.clinicaltrials.gov上注册，编号为#NCT00745550。
