Interim analysis of safety and efficacy of ruxolitinib in patients with myelofibrosis and low platelet counts.
Interim analysis of safety and efficacy of ruxolitinib in patients with myelofibrosis and low platelet counts.
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DOI：
10.1186/1756-8722-6-81
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发表时间：
2013-10-29
影响因子：
28.5
通讯作者：
Verstovsek S
中科院分区：
文献类型：
--
作者：
Talpaz M;Paquette R;Afrin L;Hamburg SI;Prchal JT;Jamieson K;Terebelo HR;Ortega GL;Lyons RM;Tiu RV;Winton EF;Natrajan K;Odenike O;Claxton D;Peng W;O'Neill P;Erickson-Viitanen S;Leopold L;Sandor V;Levy RS;Kantarjian HM;Verstovsek S
Ruxolitinib是一种Janus激酶1和2抑制剂，在III期研究中显示，与安慰剂相比，Ruxolitinib在脾脏体积、症状和生存方面都有改善，是基线血小板计数≥100 × 109/L的中2或高危骨髓纤维化患者的最佳治疗方法。最常见的不良事件是剂量依赖性贫血和血小板减少症，这是由于血小板生成素和红细胞生成素通过JAK2发出信号而预料到的。这些事件是可控的，很少导致停止治疗。由于大约四分之一的MF患者的血小板计数<100 × 109/L，因此使用较低的初始剂量对这部分患者进行了ruxolitinib评估。报告了鲁索利替尼在基线血小板计数为50-100 × 109/L的骨髓纤维化患者中的II期研究的中期结果。Ruxolitinib的起始剂量为5mg每日两次（BID），如果血小板计数保持足够，剂量可以每4周增加5mg每日一次至10mg BID。额外的剂量增加需要次优疗效的证据。评估包括MRI测量脾脏体积、MF症状评估表v2.0总症状评分（TSS）、患者整体变化印象（PGIC）；EORTC QLQ-C30，安全性/耐受性。到第24周，62%的患者达到稳定剂量≥10mg BID。脾脏体积和TSS的中位减少分别为24.2%和43.8%。需要减少剂量和中断剂量的血小板减少症患者分别有12例和8例，主要发生在基线血小板计数≤75 × 109/L的患者中。7例患者血小板升高≥15 × 109/L。平均血红蛋白水平在治疗期间保持稳定。两名患者因不良事件停药：1名患者继发于多个和疑似存在的肾动脉动脉瘤的4级腹膜后出血，1名患者4级血小板减少。结果表明，对于血小板计数低的骨髓纤维化患者，低起始剂量的鲁索利替尼（ruxolitinib）可能是合适的。ClinicalTrials.gov: NCT01348490。
Ruxolitinib, a Janus kinase 1 and 2 inhibitor, demonstrated improvements in spleen volume, symptoms, and survival over placebo and best available therapy in intermediate-2 or high-risk myelofibrosis patients with baseline platelet counts ≥100 × 109/L in phase III studies. The most common adverse events were dose-dependent anemia and thrombocytopenia, which were anticipated because thrombopoietin and erythropoietin signal through JAK2. These events were manageable, rarely leading to treatment discontinuation. Because approximately one-quarter of MF patients have platelet counts <100 × 109/L consequent to their disease, ruxolitinib was evaluated in this subset of patients using lower initial doses. Interim results of a phase II study of ruxolitinib in myelofibrosis patients with baseline platelet counts of 50-100 × 109/L are reported. Ruxolitinib was initiated at a dose of 5 mg twice daily (BID), and doses could be increased by 5 mg once daily every 4 weeks to 10 mg BID if platelet counts remained adequate. Additional dosage increases required evidence of suboptimal efficacy. Assessments included measurement of spleen volume by MRI, MF symptoms by MF Symptom Assessment Form v2.0 Total Symptom Score [TSS]), Patient Global Impression of Change (PGIC); EORTC QLQ-C30, and safety/tolerability. By week 24, 62% of patients achieved stable doses ≥10 mg BID. Median reductions in spleen volume and TSS were 24.2% and 43.8%, respectively. Thrombocytopenia necessitating dose reductions and dose interruptions occurred in 12 and 8 patients, respectively, and occurred mainly in patients with baseline platelet counts ≤75 × 109/L. Seven patients experienced platelet count increases ≥15 × 109/L. Mean hemoglobin levels remained stable over the treatment period. Two patients discontinued for adverse events: 1 for grade 4 retroperitoneal hemorrhage secondary to multiple and suspected pre-existing renal artery aneurysms and 1 for grade 4 thrombocytopenia. Results suggest that a low starting dose of ruxolitinib with escalation to 10 mg BID may be appropriate in myelofibrosis patients with low platelet counts. ClinicalTrials.gov: NCT01348490.
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影响因子：
45.3
作者：
Mesa, Ruben A.;Gotlib, Jason;Verstovsek, Srdan
通讯作者：
Verstovsek, Srdan
DOI：
10.1056/nejmoa1002028
发表时间：
2010-09-16
期刊：
The New England journal of medicine
影响因子：
--
作者：
Verstovsek S;Kantarjian H;Mesa RA;Pardanani AD;Cortes-Franco J;Thomas DA;Estrov Z;Fridman JS;Bradley EC;Erickson-Viitanen S;Vaddi K;Levy R;Tefferi A
通讯作者：
Tefferi A
DOI：
10.1056/nejmoa1110557
发表时间：
2012-03-01
期刊：
The New England journal of medicine
影响因子：
--
作者：
Verstovsek S;Mesa RA;Gotlib J;Levy RS;Gupta V;DiPersio JF;Catalano JV;Deininger M;Miller C;Silver RT;Talpaz M;Winton EF;Harvey JH Jr;Arcasoy MO;Hexner E;Lyons RM;Paquette R;Raza A;Vaddi K;Erickson-Viitanen S;Koumenis IL;Sun W;Sandor V;Kantarjian HM
通讯作者：
Kantarjian HM
影响因子：
20.3
作者：
Cervantes, Francisco;Dupriez, Brigitte;Tefferi, Ayalew
通讯作者：
Tefferi, Ayalew
影响因子：
3.7
作者：
Balduini, Alessandra;Badalucco, Stefania;Barosi, Giovanni
通讯作者：
Barosi, Giovanni