收稿日期: 2020-06-03
网络出版日期: 2021-02-28
基金资助
上海市教育委员会高峰高原学科建设计划(20152219);上海市科学技术委员会医学引导类项目(18411968300);上海申康医院发展中心临床科技创新项目(SHDC2019X02)
A pilot study on the efficacy and safety of anlotinib in the treatment of refractory natural killer/T-cell lymphoma
Received date: 2020-06-03
Online published: 2021-02-28
Supported by
Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support(20152219);Medical Guide Project of Shanghai Science and Technology Commission(18411968300);Clinical Science and Technology Innovation Project of Shanghai Shenkang Hospital Development Center(SHDC2019X2)
目的·观察安罗替尼用于治疗难治性自然杀伤/T细胞淋巴瘤（natural killer/T-cell lymphoma，NKTCL）的有效性和安全性。方法·招募于2018年8月至2019年12月在上海交通大学医学院附属新华医院门诊就诊的经病理检查确诊为NKTCL，表现为门冬酰胺酶耐药，且具有可测量/可评估病灶和一定器官功能储备的患者纳入研究；患者接受安罗替尼单药（12 mg/d）或安罗替尼（10 mg/d）联合程序性死亡蛋白-1（programmed death-1，PD-1）单克隆抗体（单抗）治疗，直至疾病进展或者不能耐受不良反应，根据Lugano 2014标准评估治疗应答。不良反应按照美国国家癌症研究所常见不良反应事件评价标准4.03版进行分级评估。Kaplan-Meier法对患者进行生存分析。结果·共12例患者纳入研究，中位年龄44岁，其中男性9例；6例患者接受安罗替尼单药治疗，6例患者接受安罗替尼联合PD-1单抗治疗。所有受试者均出现了治疗相关的不良反应，3级不良反应为高血压（2例）和低钠血症（1例），无非预期的不良反应。50.0%的患者获得客观应答，安罗替尼单药的应答率为33.3%，安罗替尼联合PD-1单抗的应答率为66.7%。中位疾病无进展生存期为3.0个月，中位总生存期（overall survival，OS）为3.0个月。接受安罗替尼单药治疗患者的中位OS为2.8个月，接受安罗替尼联合PD-1单抗治疗患者的中位OS为8.0个月；应答患者的中位OS为8.0个月，无应答患者的中位OS仅2.8个月。结论·安罗替尼可能是一个治疗难治性NKTCL的潜在药物，且与PD-1单抗具有潜在协同增效作用；该药整体安全性良好，患者普遍耐受。
关键词： 自然杀伤/T细胞淋巴瘤; 安罗替尼; 程序性死亡蛋白-1单克隆抗体
李高扬 , 姜霁峰 , 刘传绪 , 张文皓 , 朱杨 , 马玉杰 , 陶荣 . 安罗替尼治疗难治性自然杀伤/T细胞淋巴瘤的有效性与安全性的探索性研究[J]. 上海交通大学学报（医学版）, 2021 , 41(2) : 196 -201 . DOI: 10.3969/j.issn.1674-8115.2021.02.011
·To observe the efficacy and safety of anlotinib in the treatment of refractory natural killer/T-cell lymphoma (NKTCL).
·The patients who had been pathologically diagnosed as having NKTCL with measurable/assessable lesions and some organ function reserve after failing in L-asparaginase-containing regimen were recruited in this study from August 2018 to December 2019 in the Outpatient Department of Xinhua Hospital, Shanghai Jiao Tong University School of Medicine. They were given anlotinib (12 mg/d) alone or anlotinib (10 mg/d) with programmed death-1 (PD-1) monoclonal antibody until the disease progression or intolerable adverse reactions. Responses were evaluated as per Lugano 2014 criteria. Adverse reactions were assessed according to Common Terminology Criteria for Adverse Events of National Cancer Institute, USA (version 4.03). Kaplan-Meier method was used for survival analysis.
·Twelve patients were included in this study with a median age of 44 years, and 9 patients were males. Among them, 6 patients received anlotinib monotherapy, and 6 patients received anlotinib combined with PD-1 monoclonal antibody therapy. Treatment-related adverse events were observed in all 12 subjects without unexpected adverse reactions. The grade 3 adverse events included hypertension (2 cases) and hyponatremia (1 case). There were 50.0% patients obtaining objective responses with 33.3% in the anlotinib monotherapy group and 66.7% in the combined treatment group. The median progression-free survival was 3.0 months and the median overall survival (OS) was 3.0 months. The median OS of the patients receiving anlotinib alone was 2.8 months, while it was 8.0 months in the patients receiving anlotinib combined with PD-1 monoclonal antibody. The median OS of the responding patients was 8.0 months, while it was 2.8 months in the non-responding patients.
·Anlotinib may be a promising drug for the treatment of refractory NKTCL, which has a potentially synergistic effect with PD-1 monoclonal antibody; the overall safety of the drug is good, and patients generally tolerate it.
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