■这篇综述旨在确定与实体瘤的免疫检查点抑制剂(ICIs)治疗相关的胰腺不良事件(AE)的发生率和风险。
■我们在PubMed,Embase,和Cochrane图书馆截至2023年3月15日,以确定所有随机对照试验,比较ICIs与实体瘤的标准治疗。我们纳入了报道免疫相关胰腺炎或血清淀粉酶或脂肪酶水平升高的研究。在PROSPERO中注册协议之后,我们进行了系统评价和荟萃分析.
■检索了59个独特的随机对照试验,其中至少有一个含有ICI的手臂(41757名患者)。所有级别胰腺炎的发病率,淀粉酶升高和脂肪酶升高为0.93%(95%CI0.77-1.13),2.57%(95%CI1.83-3.60)和2.78%(95%CI1.83-4.19),分别。≥3级胰腺炎的发生率,淀粉酶升高和脂肪酶升高为0.68%(95%CI0.54-0.85),1.17%(95%CI0.83-1.64)和1.71%(95%CI1.18-2.49),分别。使用ICIs与包括胰腺炎在内的所有级别胰腺免疫相关AE(irAEs)的风险增加相关(OR=2.04,95%CI1.42-2.94,P=0.0001),淀粉酶升高(OR=1.91,95%CI1.47-2.49,P<0.0001)和脂肪酶升高(OR=1.77,95%CI1.37-2.29,P<0.0001)。除了这些,事后分析发现,与PD-L1抑制剂相比,PD-1抑制剂发生胰腺AE的风险显著更高,并且与接受单一ICI治疗的患者相比,接受双重ICI治疗的患者发生胰腺AE的风险显著更高.
■我们的研究概述了实体瘤治疗中ICI相关胰腺炎和胰酶升高的发生率和风险。我们的发现可能有助于提高临床医生对临床实践中ICI相关胰腺AE的潜在认识。
■https://www.crd.约克。AC.英国/PROSPERO,标识符345350。
This
review aims to determine the incidence and risk of pancreatic adverse events (AEs) associated with immune checkpoint inhibitors (ICIs) therapy for solid tumors.
We conducted a comprehensive systematic literature search in PubMed, Embase, and Cochrane Library up to March 15, 2023, to identify all randomized controlled trials comparing ICIs with standard treatment in solid tumors. We included studies that reported immune-related pancreatitis or elevation of serum amylase or lipase levels. Following protocol registration in PROSPERO, we conducted a systematic
review and meta-analysis.
59 unique randomized controlled trials with at least one ICI-containing arm (41 757 patients) were retrieved. The incidences for all-grade pancreatitis, amylase elevation and lipase elevation were 0.93% (95% CI 0.77-1.13), 2.57% (95% CI 1.83-3.60) and 2.78% (95% CI 1.83-4.19), respectively. The incidences for grade ≥3 pancreatitis, amylase elevation and lipase elevation were 0.68% (95% CI 0.54-0.85), 1.17% (95% CI 0.83-1.64) and 1.71% (95% CI 1.18-2.49), respectively. The use of ICIs was associated with an increased risk of all-grade pancreatic immune-related AEs (irAEs) including pancreatitis (OR=2.04, 95% CI 1.42-2.94, P =0.0001), amylase elevation (OR=1.91, 95% CI 1.47-2.49, P < 0.0001) and lipase elevation (OR=1.77, 95% CI 1.37-2.29, P < 0.0001). In addition to these, the post-hoc analysis found that PD-1 inhibitors had a significant higher risk of pancreatic AEs compared with PD-L1 inhibitors and the patients undergoing dual ICI therapy were at a significantly higher risk of pancreatic AEs than the patients receiving single ICI therapy.
Our study provides an overview of the incidence and risk of ICI-associated pancreatitis and pancreatic enzyme elevations in the treatment of solid tumors. Our findings may help raise awareness among clinicians of the potential for ICI-associated pancreatic AEs in clinical practice.
https://www.crd.york.ac.uk/PROSPERO, identifier 345350.