替雷利珠单抗致不良反应的文献分析

目的 分析替雷利珠单抗不良反应的临床表现和特点,为临床安全用药提供参考。方法 检索中国知网、万方、维普、PubMed、Embase、Web of Science等数据库有关替雷利珠单抗导致不良反应的文献报道,并进行整理分析。结果 共收集到替雷利珠单抗导致不良反应的文献报道17篇,18例患者,其中男性13例（72.2%）、女性5例（27.8%）,年龄分布在60岁以上居多（72.2%）,发生时间大多在用药后3个月内（72.2%）,替雷利珠单抗致不良反应以皮肤及其附件损害最多见（6例,33.3%）,17例经停药和对症治疗好转,1例因继发肺部感染死亡。结论 替雷利珠单抗致不良反应累及多个器官/系统,应增强监测,防范严重不良反应的发生,确保用药安全。     

Tislelizumab in Asian patients with previously treated locally advanced or metastatic urothelial carcinoma

Tislelizumab, an anti‐programmed death protein‐1 (PD‐1) monoclonal antibody, was engineered to minimize binding to the FcγR on macrophages to abrogate antibody‐dependent phagocytosis, a mechanism of T‐cell clearance and potential resistance to anti‐PD‐1 therapy. This single‐arm phase 2 trial ({"type":"clinical-trial","attrs":{"text":"NCT04004221","term_id":"NCT04004221"}}NCT04004221/CTR20170071) assessed the safety, tolerability, and efficacy of tislelizumab in patients with PD‐L1‐positive urothelial carcinoma who progressed during/following platinum‐containing therapy and had no prior PD‐(L)1 inhibitor treatment. Patients were considered PD‐L1 positive if ≥ 25% of tumor/immune cells expressed PD‐L1 when using the VENTANA™ PD‐L1 (SP263) assay. The primary endpoint was objective response rate by independent review committee. As of September 16, 2019, 113 patients had a median study follow‐up time of 9.4 mo. Most patients (76%) had visceral metastases, including 24% with liver and 23% with bone metastases. Among 104 efficacy‐evaluable patients, confirmed objective response rate was 24% (95% confidence interval, 16, 33), including 10 complete and 15 partial responses. Median duration of response was not reached. Among 25 responders, 17/25 (68%) had ongoing responses. Median progression‐free survival and overall survival times were 2.1 and 9.8 mo, respectively. The most common treatment‐related adverse events were anemia (27%) and pyrexia (19%). Anemia (7%) and hyponatremia (5%) were the only grade 3‐4 treatment‐related adverse events and occurred in ≥ 5% of patients. Three investigator‐assessed deaths were considered to be possibly related to study treatment (hepatic failure, n = 2; respiratory arrest, n = 1). Tislelizumab demonstrated meaningful clinical benefits in patients with previously treated locally advanced or metastatic PD‐L1‐positive urothelial carcinoma and had a manageable safety profile.     

Clinical outcomes and influencing factors of PD-1/PD-L1 in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) has an increasing incidence worldwide, and the global 5-year survival rate ranges from 5–30%. In China, HCC seriously threatens the nation''s health; the incidence of HCC ranks fourth among all theriomas, and the mortality rate is the third highest worldwide. The main therapies for HCC are surgical treatment or liver transplantation; however, most patients with HCC will experience postoperative recurrence or metastasis, eventually resulting in mortality. As for advanced or unresectable HCC, the current appropriate treatment strategy is transarterial chemoembolization; however, limited therapeutic effect and natural or acquired drug resistance affect the efficacy of this approach. Previous studies have demonstrated that PD-L1 expression on host cells and myeloid cells plays an important role in PD-L1 blocked-mediated tumor regression. Thus, further research on programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) is required. Countries including the United States, France, Britain and China have developed PD-1/PD-L1 blockers, including nivolumab, pembrolizumab, cemiplimab, atezolizumab, avelumab, durvalumab, toripalimab, sintilimab and camrelizumab. Notably, all of these blockers have therapeutic effect and influencing factors in HCC. Factors that influence the clinical outcome of PD-1 have also been discovered, such as inflammatory genes, specific receptors and signaling pathways. The discovery of these factors will help to identify novel methods, such as combination treatment, to decrease the influence of other factors on the efficacy of PD-1/PD-L1. Sorafenib and lenvatinib have been approved for first-line treatment for patients with advanced HCC. When first-line treatment frequently fails, pembrolizumab and ipilimumab plus nivolumab are used following sorafenib (but not lenvatinib) treatment in advanced HCC. Thus, tumor immunotherapy using PD-1/PD-L1 blockers exhibits promising outcomes for the treatment of HCC, and more novel PD-1/PD-L1 inhibitors are being developed to fight against this disease. The present review discusses the clinical results and influencing factors of PD-1/PD-L1 inhibitors in HCC to provide insight into the development and optimization of PD-1/PD-L1 inhibitors in the treatment of HCC.     

替雷利珠单抗相关药物不良反应文献分析

目的：归纳替雷利珠单抗引起药物不良反应（adverse drug reactions,ADRs）的特点,为临床用药安全提供参考。方法：检索中国知网、万方、维普、PubMed、ScienceDirect 和 Embase 数据库（截至2022年4月）,收集关于替雷利珠单抗相关ADRs的个案报道,对纳入病例的临床资料、替雷利珠单抗用药情况以及ADRs的临床表现、名称、发生时间、处置及转归等进行统计分析。结果：纳入替雷利珠单抗致ADRs的个案报道15篇,共计16例患者,其中男性11例,女性5例;年龄26~78岁,平均年龄（64.81±12.92）岁。ADRs发生时间在1个用药周期内的有4例,2个用药周期内的有2例,3~9周期时间内8例,10个周期后的有2例;涉及皮肤软组织、内分泌、消化、泌尿和心血管等系统,经对症治疗后,16例患者均好转。结论：临床使用中应加强替雷利珠单抗相关ADRs的关注,提高临床用药安全性。     

4种准入中国医保的PD-1抑制剂药学特性及临床应用评价

PD-1抑制剂是一种免疫检查点抑制剂，其通过阻断PD-1/PD-L1信号通路可使T细胞活化上调，激活内源性抗肿瘤免疫反应，从而发挥对肿瘤的治疗作用，已成为肿瘤治疗领域中最大的突破。2020年12月中国公布的新版医保目录中，有4种PD-1抑制剂通过药品谈判准入，并于2021年3月1日正式执行医保报销。鉴于进入医保的4种PD-1抑制剂，上市时间较短，尚缺乏较为系统、全面的药学评价，故本研究对这4种PD-1抑制剂药学特点、药品说明书适应证、医保获批适应证及临床应用等内容进行总结评价，以期为中国临床合理使用PD-1抑制剂提供参考。     

免疫检查点抑制剂相关Stevens-Johnson综合征一例

本文报道1例经13程替雷利珠单抗治疗肺腺癌的37岁男性患者,使用伏美替尼1个月后出现Stevens-Johnson综合征(SJS),自行服用安罗替尼1天后加重,诊断为SJS,CTCAE分级3级,经激素冲击治疗后1个月内恢复。免疫检查点抑制剂、表皮生长因子抑制剂、多激酶抑制剂均可以引起角质形成细胞凋亡,导致SJS/TEN,其中免疫治疗导致的SJS/TEN病情重、死亡率高,免疫治疗后使用靶向药物会提高严重皮肤不良事件的发生率。在免疫治疗后引入靶向治疗,脱敏可能是必要的。     

2020—2022年辽宁省肿瘤医院免疫检查点抑制剂的使用情况分析

目的 分析辽宁省肿瘤医院2020—2022年免疫检查点抑制剂的使用情况以及变化趋势，为规范其管理及临床合理使用提供参考。方法 收集2020—2022年辽宁省肿瘤医院免疫检查点抑制剂使用数据，分析销售金额、用药频度（DDDs）、限定日费用（DDC）以及排序比（B/A）。结果 2020—2022年免疫检查点抑制剂销售金额大幅增长。帕博利珠单抗和替雷利珠单抗使用金额较大，排名靠前。2022年新增的品种（阿替利珠单抗、卡度尼利单抗、赛帕利单抗、斯鲁利单抗、舒格利单抗、恩沃利单抗）销售金额排名靠后。替雷利珠单抗的DDDs近3年大幅增加。卡度尼利单抗、度伐利尤单抗、帕博利珠单抗、纳武利尤单抗DDC值偏高，且B/A＜1。信迪利单抗、替雷利珠单抗、卡瑞利珠单抗、特瑞普利单抗DDC在2022年有大幅度的下降，DDC值较低，且B/A＞1。结论 2020—2022年辽宁省肿瘤医院免疫检查点抑制剂的使用总体上比较合理，但仍需进一步加强监管力度，保障患者用药的安全、有效和经济。     

替雷利珠单抗致中毒性表皮坏死松解症1例报告

目的 了解程序性细胞死亡受体-1（programmed cell death-1,PD-1）/程序性细胞死亡受体-配体1（programmed cell death-ligand 1,PD-L1）抑制剂治疗肿瘤导致Stevens-Johnson综合征（Stevens-Johnson syndrome,SJS）/中毒性表皮坏死松解症（toxic epidermal necrolysis,TEN）的临床特点。方法 回顾性分析海军军医大学第三附属医院皮肤科诊治的1例及既往文献报道的31例PD-1/PD-L1抑制剂治疗肿瘤导致SJS/TEN的临床资料。结果 共收集32例，其中SJS 15例，潜伏期平均8.4周，SJS-TEN 3例，潜伏期平均2.5周，TEN 14例，潜伏期平均3.8周。好转21例，转为慢性扁平苔鲜1例，加重1例，死亡8例，未报道1例。结论PD-1/PD-L1抑制剂治疗肿瘤导致SJS/TEN少见但危重，需引起临床医师的高度重视。     

Tislelizumab plus chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal cancer: A multicenter phase 3 trial (RATIONALE-309)

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