β-glucan combined with Envafolimab and Endostar as immune rechallenge for metastatic non-small cell lung cancer

IF 2.9 4区 医学 Q3 IMMUNOLOGY BMC Immunology Pub Date : 2024-09-14 DOI:10.1186/s12865-024-00651-x
Qian Geng, Yingying Lu, Dongqing Li, Lanqun Qin, Chunjian Qi, Xiaolin Pu, Yi Zhuang, Yajun Zhu, Quanbin Zha, Ge Wang, Hua Jiang
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Abstract

Immune checkpoint inhibitor rechallenge has emerged as a prominent study area in non-small cell lung cancer (NSCLC). β-glucan was reported to reverse resistance to anti-PD-1/PD-L1 inhibitors by regulating the tumor microenvironment. In this self-initiated clinical trial (ChiCTR2100054796), NSCLC participants who have previously failed anti-PD-1 therapy received β-glucan (500 mg, bid, d1-21), Envafolimab (300 mg, d1) and Endostar (210 mg, civ72h) every 3 weeks until disease progression or unacceptable toxicity. The clinical efficacy and adverse events were observed, while serum samples were collected for proteomic analysis. Twenty Three patients were enrolled from January 2022 to March 2023 (median age, 65 years; male, n = 18 [78.3%]; squamous NSCLC, n = 9 [39.1%]; mutant type, n = 13 [56.5%]). The overall response rate (ORR) was 21.7% and disease control rate (DCR) was 73.9%. Median progression-free survival (mPFS) and median overall survival (mOS) was 4.3 months [95% CI: 2.0–6.6] and 9.8 months [95% CI: 7.2–12.4], respectively. The mPFS between PD-L1 positive and negative subgroup has significant difference (6.3 months vs. 2.3 months, p = 0.002). Treatment-related adverse events (TRAEs) occurred in 52.2% of patients. The most common TRAEs were hypothyroidism (26.1%) and fatigue (26.1%). 2 (8.7%) grade 3 adverse events were reported. No adverse reaction related deaths have been observed. Proteomic analysis revealed that the levels of CASP-8, ARG1, MMP12, CD28 and CXCL5 correlated with resistance to the treatment while the levels of CD40-L and EGF related to the favorable response. β-glucan combined with Envafolimab and Endostar has considerable efficacy and safety for immune rechallenge in metastatic NSCLC patients who failed of anti-PD-1 treatment previously, especially for PD-L1 positive patients.
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β-葡聚糖与恩伐利单抗和 Endostar 联合作为转移性非小细胞肺癌的免疫再挑战疗法
免疫检查点抑制剂再挑战已成为非小细胞肺癌(NSCLC)的一个重要研究领域。据报道,β-葡聚糖可通过调节肿瘤微环境来逆转抗PD-1/PD-L1抑制剂的耐药性。在这项自发的临床试验(ChiCTR2100054796)中,既往抗PD-1治疗失败的NSCLC参与者每3周接受一次β-葡聚糖(500毫克,bid,d1-21)、恩华利单抗(300毫克,d1)和Endostar(210毫克,civ72h)治疗,直至疾病进展或出现不可接受的毒性。观察临床疗效和不良反应,同时收集血清样本进行蛋白质组分析。从 2022 年 1 月到 2023 年 3 月,共招募了 23 名患者(中位年龄 65 岁;男性,n = 18 [78.3%];鳞状 NSCLC,n = 9 [39.1%];突变型,n = 13 [56.5%])。总反应率(ORR)为21.7%,疾病控制率(DCR)为73.9%。中位无进展生存期(mPFS)和中位总生存期(mOS)分别为4.3个月[95% CI:2.0-6.6]和9.8个月[95% CI:7.2-12.4]。PD-L1阳性亚组和阴性亚组的mPFS差异显著(6.3个月 vs. 2.3个月,P = 0.002)。52.2%的患者发生了治疗相关不良事件(TRAEs)。最常见的不良反应是甲状腺功能减退(26.1%)和疲劳(26.1%)。报告了 2 例(8.7%)3 级不良反应。未发现与不良反应相关的死亡病例。蛋白质组分析显示,CASP-8、ARG1、MMP12、CD28和CXCL5的水平与治疗耐药性相关,而CD40-L和EGF的水平与良好反应相关。β-葡聚糖与恩伐利单抗和恩度斯达联合治疗既往抗PD-1治疗失败的转移性NSCLC患者,尤其是PD-L1阳性患者的免疫再挑战具有相当高的疗效和安全性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
BMC Immunology
BMC Immunology 医学-免疫学
CiteScore
5.50
自引率
0.00%
发文量
54
审稿时长
1 months
期刊介绍: BMC Immunology is an open access journal publishing original peer-reviewed research articles in molecular, cellular, tissue-level, organismal, functional, and developmental aspects of the immune system as well as clinical studies and animal models of human diseases.
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