Departments of Gastroenterology, Hepatology & Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Minimally Invasive Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People's Republic of China.
J Immunother Cancer. 2019 Feb 6;7(1):31. doi: 10.1186/s40425-019-0502-7.
Immune checkpoint inhibitor (ICI)-induced pancreatic injury (ICIPI) is not well documented in the literature. We aimed to describe the clinical characteristics and outcomes of patients who developed ICIPI.
We reviewed the medical records of consecutive patients who had a confirmed diagnosis of ICIPI (Common Terminology Criteria for Adverse Events grade ≥ 3 lipase elevation with or without clinical symptoms) from April 2011 through April 2018.
Among the 2,279 patients received ICI and had lipase values checked thereafter, 82 (4%) developed ICIPI. Overall, 65% of patients received inhibitors of programmed death protein-1 or its ligand. Compared with asymptomatic presentation, patients who had clinical symptoms of pancreatitis (n = 32) had higher levels of lipase (P = 0.032), more frequent imaging evidence of pancreatitis (P = 0.055), and more frequent hospitalization (P < 0.001) and received intravenous fluids (P < 0.001) and steroids more frequently (P = 0.008). Twelve patients (15%) developed long-term adverse outcomes of ICIPI; three had chronic pancreatitis, four had recurrence of ICIPI, and six had subsequent diabetes. Among 35 patients who resumed ICI therapy, four (11%) had recurrence of lipase elevation. Logistic regression revealed that smoking and hyperlipidemia were associated with increased risk for long-term adverse outcomes of ICIPI, and intravenous fluids were associated with reduced risk. Patients who resumed ICI therapy survived longer than patients who discontinued ICI therapy permanently, statistically not significant (P = 0.0559). Patients who developed long-term adverse outcomes of ICIPI survived significantly longer than those who did not (P = 0.0295). The highest proportion of patients (6/21, 29%) developed long-term adverse outcomes of ICIPI was among those without typical symptoms of pancreatitis, continued ICI therapy after ICIPI, and did not receive intravenous fluids.
ICIPI can present as typical acute pancreatitis, with risk of the development of a pseudocyst, diabetes, and chronic pancreatitis. ICI resumption after ICIPI may lead to recurrence of lipase elevation without increased risk of long-term adverse outcomes, and can increase survival duration. Intravenous fluids may prevent long-term adverse outcomes, but steroids do not appear to affect outcomes of ICIPI. Asymptomatic ICIPI presentation may lead to undertreatment of ICIPI owing to underestimation of its degree, and therefore, intravenous fluid administration could potentially could potentially be benificial to prevent long-term adverse outcomes even in asymptomatic patients.
免疫检查点抑制剂（ICI）诱导的胰腺损伤（ICIPI）在文献中报道较少。我们旨在描述发生 ICIPI 的患者的临床特征和结局。
我们回顾了 2011 年 4 月至 2018 年 4 月期间确诊为 ICIPI（不良事件通用术语标准≥3 级脂肪酶升高，伴有或不伴有临床症状）的连续患者的病历。
在接受 ICI 治疗并随后检查脂肪酶值的 2279 名患者中，有 82 名（4%）发生了 ICIPI。总体而言，65%的患者接受了程序性死亡蛋白-1 或其配体抑制剂的治疗。与无症状表现相比，有胰腺炎临床症状的患者（n=32）的脂肪酶水平更高（P=0.032），胰腺炎的影像学证据更频繁（P=0.055），住院治疗更频繁（P<0.001），更常接受静脉补液（P<0.001）和皮质类固醇治疗（P=0.008）。12 名患者（15%）发生了 ICIPI 的长期不良结局；3 名患者患有慢性胰腺炎，4 名患者复发 ICIPI，6 名患者继发糖尿病。在 35 名重新开始 ICI 治疗的患者中，有 4 名（11%）出现脂肪酶升高复发。逻辑回归显示，吸烟和高脂血症与 ICIPI 的长期不良结局风险增加相关，而静脉补液与风险降低相关。重新开始 ICI 治疗的患者比永久停止 ICI 治疗的患者存活时间更长，但统计学上无显著差异（P=0.0559）。发生 ICIPI 长期不良结局的患者比未发生的患者存活时间更长（P=0.0295）。在没有典型胰腺炎症状、发生 ICIPI 后继续接受 ICI 治疗且未接受静脉补液的患者中，有 6 名患者（29%）发生 ICIPI 的长期不良结局的比例最高。
ICIPI 可表现为典型的急性胰腺炎，有发展为假性囊肿、糖尿病和慢性胰腺炎的风险。发生 ICIPI 后重新开始 ICI 治疗可能会导致脂肪酶升高复发，但不会增加长期不良结局的风险，并能延长生存时间。静脉补液可能预防长期不良结局，但皮质类固醇似乎不会影响 ICIPI 的结局。无症状的 ICIPI 表现可能会由于对其严重程度的低估而导致对 ICIPI 的治疗不足，因此，即使在无症状患者中，静脉补液也可能有助于预防长期不良结局。
