Burke John M, Shustov Andrei, Essell James, Patel-Donnelly Dipti, Yang Jay, Chen Robert, Ye Wei, Shi Wen, Assouline Sarit, Sharman Jeff
Rocky Mountain Cancer Centers, The US Oncology Network, Aurora, CO.
University of Washington School of Medicine, Seattle, WA.
Clin Lymphoma Myeloma Leuk. 2018 Aug;18(8):e327-e331. doi: 10.1016/j.clml.2018.05.022. Epub 2018 Jun 6.
Entospletinib (GS-9973) is an oral, selective inhibitor of spleen tyrosine kinase. Entospletinib monotherapy was evaluated in a multicenter, phase II study of subjects with relapsed or refractory B-cell malignancy.
The study included 43 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The participants received 800 mg of the original, monomesylate formulation of entospletinib twice daily as a starting dose; the doses could be reduced because of toxicity throughout the study.
No patient achieved a complete or partial response, 5 patients (12%) had stable disease, and 26 patients (60%) had progressive disease. Progression-free survival (PFS) at 16 weeks was 3.6% (95% confidence interval [CI], 0.3%-15.3%), and the median PFS was 1.5 months (95% CI, 1-1.7 months). The independent review committee-assessed nodal response for 27 evaluable patients showed a reduced tumor burden in 6 patients (22%). The median duration of entospletinib treatment for these 6 patients was 9 weeks (range, 3-24 weeks). One patient (4%) had a decrease of ≥ 50% in the sum of the product of the nodal diameters. The treatment-emergent adverse events occurring in ≥ 20% of the cohort were fatigue, nausea, decreased appetite, constipation, dyspnea, diarrhea, dehydration, cough, insomnia, and peripheral edema. The common laboratory abnormalities occurring in ≥ 20% of the subjects were lymphocytopenia, anemia, creatinine (chronic kidney disease), increased aspartate aminotransferase, hypoalbuminemia, total bilirubin, hyponatremia, leukopenia, increased alanine aminotransferase, increased alkaline phosphatase, and hyperglycemia.
Entospletinib monotherapy at 800 mg twice daily demonstrated limited activity in patients with advanced, relapsed DLBCL.
恩托司替尼（GS-9973）是一种口服的脾酪氨酸激酶选择性抑制剂。在一项针对复发或难治性B细胞恶性肿瘤患者的多中心II期研究中对恩托司替尼单药治疗进行了评估。
该研究纳入了43例复发或难治性弥漫性大B细胞淋巴瘤（DLBCL）患者。参与者接受800mg恩托司替尼原研单甲磺酸盐制剂，每日两次作为起始剂量；在整个研究过程中，剂量可因毒性而降低。
无患者达到完全缓解或部分缓解，5例患者（12%）疾病稳定，26例患者（60%）疾病进展。16周时的无进展生存期（PFS）为3.6%（95%置信区间[CI]，0.3%-15.3%），中位PFS为1.5个月（95%CI，1-1.7个月）。独立审查委员会评估的27例可评估患者的淋巴结反应显示，6例患者（22%）肿瘤负荷减轻。这6例患者接受恩托司替尼治疗的中位持续时间为9周（范围3-24周）。1例患者（4%）淋巴结直径乘积总和下降≥50%。在≥20%的队列中发生的治疗中出现的不良事件为疲劳、恶心、食欲减退、便秘、呼吸困难、腹泻、脱水、咳嗽、失眠和外周水肿。在≥20%的受试者中出现的常见实验室异常为淋巴细胞减少、贫血、肌酐（慢性肾病）、天冬氨酸转氨酶升高、低白蛋白血症、总胆红素、低钠血症、白细胞减少、丙氨酸转氨酶升高、碱性磷酸酶升高和高血糖。
每日两次800mg恩托司替尼单药治疗在晚期复发DLBCL患者中显示出有限的活性。
