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脂肪酶升高与免疫检查点抑制剂治疗相关的1型糖尿病——来自德国皮肤肿瘤学组的90例患者的多中心研究

Lipase elevation and type 1 diabetes mellitus related to immune checkpoint inhibitor therapy - A multicentre study of 90 patients from the German Dermatooncology Group.

作者信息

Grimmelmann Imke, Momma Michael, Zimmer Lisa, Hassel Jessica C, Heinzerling Lucie, Pföhler Claudia, Loquai Carmen, Ruini Cristel, Utikal Jochen, Thoms Kai-Martin, Kähler Katharina C, Eigentler Thomas, Herbst Rudolf A, Meier Friedegund, Debus Dirk, Berking Carola, Kochanek Corinna, Ugurel Selma, Gutzmer Ralf

机构信息

Skin Cancer Center Hannover, Department of Dermatology, Hannover Medical School, Carl Neuberg Str. 1, 30625, Hannover, Germany.

Diabetes Center L1, Lohstrasse 1-2, 31785, Hameln, Germany.

出版信息

Eur J Cancer. 2021 May;149:1-10. doi: 10.1016/j.ejca.2021.02.017. Epub 2021 Mar 31.

DOI:
10.1016/j.ejca.2021.02.017
PMID:33812141
Abstract

AIM

Immune checkpoint inhibition (ICI) triggers immune-related adverse events (irAEs). The relevance of lipase elevation remains unclear.

PATIENTS AND METHODS

Skin cancer patients with newly detected serum lipase elevation (at least twofold upper normal limit) or newly diagnosed type I diabetes mellitus upon ICI therapy were retrospectively collected at 14 German skin cancer centres.

RESULTS

We identified 68 patients with lipase elevation occurring after a median time of 19 (range 1-181) weeks on ICI, 15 (22%) thereof had symptoms consistent with pancreatitis. Forty-seven patients (73%) had other irAE, mainly colitis. Discontinuation (n = 24, 35%) or interruption (n = 26, 38%) of ICI resulted in decrease of lipase after reinduction of ICI lipase levels increased again in 12 of 24 patients. In 18 patients (27%), ICI was continued unchanged, and in 12 (67%) of them, lipase levels normalised. Twenty-two patients were identified with newly diagnosed type I diabetes mellitus related to ICI, and 12 (55%) thereof had also lipase elevation mainly shortly before or after the diagnosis of diabetes. Fourteen (64%) patients had other irAE, mainly thyroiditis. Irrespective of lipase elevation, patients frequently showed a rapid onset with ketoacidosis, decreased c-peptide, and strongly increased blood glucose levels.

CONCLUSION

Increased serum lipase during ICI is often not associated with pancreatitis but with other irAE as possible cause. Therefore, it might be sufficient to regularly monitor blood glucose levels and perform further workup only in case of signs or symptoms of pancreatitis and/or exocrine pancreas insufficiency.

摘要

目的

免疫检查点抑制(ICI)引发免疫相关不良事件(irAE)。脂肪酶升高的相关性仍不明确。

患者与方法

在德国14个皮肤癌中心回顾性收集了接受ICI治疗后新检测出血清脂肪酶升高(至少两倍于正常上限)或新诊断为I型糖尿病的皮肤癌患者。

结果

我们确定了68例在ICI治疗中位时间19周(范围1 - 181周)后出现脂肪酶升高的患者,其中15例(22%)有与胰腺炎相符的症状。47例患者(73%)有其他irAE,主要是结肠炎。ICI停药(n = 24,35%)或中断(n = 26,38%)后脂肪酶水平下降,再次诱导ICI后,24例患者中有12例脂肪酶水平再次升高。18例患者(27%)继续使用未改变的ICI,其中12例(67%)脂肪酶水平恢复正常。确定了22例与ICI相关的新诊断为I型糖尿病的患者,其中12例(55%)在糖尿病诊断前后不久也有脂肪酶升高。14例(64%)患者有其他irAE,主要是甲状腺炎。无论脂肪酶是否升高,患者常表现为酮症酸中毒迅速发作、C肽降低和血糖水平大幅升高。

结论

ICI治疗期间血清脂肪酶升高通常与胰腺炎无关,而可能与其他irAE有关。因此,定期监测血糖水平可能就足够了,仅在出现胰腺炎和/或外分泌胰腺功能不全的体征或症状时进行进一步检查。

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