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

Grimmelmann, Imke; Momma, M.; 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; Meier, Friedegund; Debus, Dirk; Berking, Carola; Kochanek, Corinna; Ugurel, Selma; Gutzmer, Ralf

doi:10.1016/j.ejca.2021.02.017

Cited by 16 publications

(25 citation statements)

References 19 publications

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“…Interestingly, routine blood tests revealed marginal associations with Blastocystis infection; patients with an abnormal lipase index (OR = 3.90, 95% CI: 0.78-19.58) were more likely to infect with Blastocystis compared to those with a normal index. Such elevation of lipase is regularly observed during immune checkpoint inhibition (ICI) [40]. We speculate that the elevation seen in our cohort might reflect such immune suppression.…”

Section: Discussionsupporting

confidence: 66%

Echinococcosis Is Associated with the Increased Prevalence of Intestinal Blastocystis Infection in Tibetans and Host Susceptibility to the Blastocystis in Mice

Zou

Wang

Liu

et al. 2022

Biology

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Blastocystis is a common human intestinal protozoan parasite. Little is known about its prevalence in echinococcosis. This study tested whether Echinococcus multilocularis infection would increase host susceptibility to Blastocystis. A total of 114 fecal samples (68 hydatid disease patients and 46 healthy people) were collected from Tibetans in the Qinghai province in China. The presence of Blastocystis was identified by sequencing of the small subunit (SSU) rRNA gene. Balb/c mice were co-infected with Blastocystis and E. multilocularis and tested for host susceptibility to Blastocystis. The overall Blastocystis prevalence was 12.3%; 16.2% in the patients and 4.4% in healthy people (p < 0.05). Sequence analysis identified three known Blastocystis genotypes, including ST1, ST2, and ST3, and one unknown genotype. Experimental dual infection significantly reduced mouse survival rate (20%), induced more severe signs, and increased intestinal damages with a higher intestinal colonization level of Blastocystis. The mouse model showed that E. multilocularis infection increases host susceptibility to Blastocystis. Our study shows a significantly higher prevalence of Blastocystis in patients with liver echinococcosis and reveals that non-intestinal E. multilocularis infection increases host susceptibility to the Blastocystis. Our results highlight that E. multilocularis infection is associated with Blastocystis. These findings remind us that more attention should be paid to the gut health of the patients with a helminth infection during clinical patient care.

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Section: Discussionsupporting

confidence: 66%

Echinococcosis Is Associated with the Increased Prevalence of Intestinal Blastocystis Infection in Tibetans and Host Susceptibility to the Blastocystis in Mice

Zou

Wang

Liu

et al. 2022

Biology

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“…ICI-associated diabetes mellitus (ICI-DM) is defined as new-onset insulin-dependent diabetes, characterized by an acute attack of dramatic hyperglycemia with the destruction of beta cells and severe insulin deficiency (Stamatouli et al, 2018;de Filette et al, 2019;Quandt et al, 2020). A retrospective study has reported that lipase elevation is mainly caused by extrapancreatic AEs such as colitis rather than pancreatitis (Grimmelmann et al, 2021). Considering that the relevance of lipase elevation with ICI-associated pancreatitis (ICI-P) remains controversial (Friedman et al, 2017;Grimmelmann et al, 2021), pancreatic enzyme elevation was excluded from the study.…”

Section: Adverse Event and Drug Identificationmentioning

confidence: 99%

“…A retrospective study has reported that lipase elevation is mainly caused by extrapancreatic AEs such as colitis rather than pancreatitis (Grimmelmann et al, 2021). Considering that the relevance of lipase elevation with ICI-associated pancreatitis (ICI-P) remains controversial (Friedman et al, 2017;Grimmelmann et al, 2021), pancreatic enzyme elevation was excluded from the study. Based on previous reports (Raschi et al, 2013;Friedman et al, 2017;Eshet et al, 2018;Stamatouli et al, 2018;Wright et al, 2018;Abu-Sbeih et al, 2019;de Filette et al, 2019;Liu et al, 2020;Porcu et al, 2020;Quandt et al, 2020;Grimmelmann et al, 2021;Liu et al, 2021), the PTs of ICIPI selected from the Medical Dictionary for Regulatory Activities (MedDRA) and included in this study are provided in Supplementary Table S1.…”

Section: Adverse Event and Drug Identificationmentioning

confidence: 99%

Pancreatic Adverse Events Associated With Immune Checkpoint Inhibitors: A Large-Scale Pharmacovigilance Analysis

Zhang

Fang

et al. 2022

Front. Pharmacol.

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Backgrounds: Immune checkpoint inhibitors (ICIs) are considered cornerstones of oncology treatment with durable anti-tumor efficacy, but the increasing use of ICIs is associated with the risk of developing immune-related adverse events (irAEs). Although ICI-associated pancreatic adverse events (AEs) have been reported in patients treated with ICIs, the clinical features and spectrum of pancreatic AEs are still not well-defined. Therefore, this study aimed to identify the association between pancreatic AEs and ICIs treatments and to characterize the main features of ICI-related pancreatic injury (ICIPI) based on the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: Data from the first quarter of 2015 to the first quarter of 2021 in the database were extracted to conduct a disproportionality analysis. The selection of AEs related to the pancreas relied on previous studies and preferred terms from the Medical Dictionary for Regulatory Activities. Two main disproportionality analyses—the reporting odds ratio (ROR) and information component (IC)—were used to evaluate potential associations between ICIs and pancreatic AEs. Results: In total, 2,364 cases of pancreatic AEs in response to ICIs were extracted from the FAERS database, of which, 647 were identified as ICI-associated pancreatitis and 1,293 were identified as ICI-associated diabetes mellitus. Generally, significant signals can be detected between pancreatic AEs and all ICIs treatments (ROR025 = 3.30, IC025 = 1.71). For monotherapy, the strongest signal associated with pancreatitis was reported for anti-PD-L1 (ROR025 = 1.75, IC025 = 0.76), whereas that with diabetes mellitus was reported for anti-PD-1 (ROR025 = 6.39, IC025 = 2.66). Compared with monotherapy, combination therapy showed stronger associations with both ICI-associated pancreatitis (ROR025 = 2.35, IC025 = 1.20 vs. ROR025 = 1.52, IC025 = 0.59) and ICI-associated diabetes mellitus (ROR025 = 9.53, IC025 = 3.23 vs. ROR025 = 5.63, IC025 = 2.48), but lower fatality proportion. Conclusions: ICIs were significantly associated with the over-reporting frequency of pancreatic AEs, in which combination therapy posed a higher reporting frequency. Therefore, patients should be informed of these potential toxicities before ICIs medications are administered.

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“…Although lipase elevation is a common side effect of ICI, the medical significance remains uncertain. Recently, a multicentric study from the German Dermatooncology Group examined the relevance of lipase elevation and type I diabetes in melanoma patients treated with ICI [4]. In 68 patients with lipase elevation of at least >2.0 x upper limit normal (ULN) and a median of 6.4 x ULN, only 22% of the patients showed symptoms of pancreatitis, whereas 78% of the patients were asymptomatic.…”

Section: Lipase Elevationmentioning

confidence: 99%

From Lipase Elevation to Diabetes – Pancreatic Involvement during Immune Checkpoint Inhibition

2023

Journal of Cellular Immunology

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Nowadays, as a standard of care treatment of several cancers, immune checkpoint inhibitors have changed the field of oncology. However, their empowerment of T cell-mediated anti-tumor immunity bears the risk for injury of various organs as a side effect. Many years of treatment with immune checkpoint inhibitors have taught oncologists the management of common immune-related adverse events such as cutaneous, gastrointestinal, lung and cardiovascular toxicities. Nonetheless, there is still a lack of knowledge about different mechanisms, significance and management of pancreatic involvement during immune checkpoint inhibition. In this review, we examine the current evidence on lipase elevation, acute pancreatitis, diabetes mellitus and pancreatic exocrine insufficiency related to immune checkpoint inhibition. We further present approaches of diagnosis and management of these adverse events.

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

Cited by 16 publications

References 19 publications

Echinococcosis Is Associated with the Increased Prevalence of Intestinal Blastocystis Infection in Tibetans and Host Susceptibility to the Blastocystis in Mice

Echinococcosis Is Associated with the Increased Prevalence of Intestinal Blastocystis Infection in Tibetans and Host Susceptibility to the Blastocystis in Mice

Pancreatic Adverse Events Associated With Immune Checkpoint Inhibitors: A Large-Scale Pharmacovigilance Analysis

From Lipase Elevation to Diabetes – Pancreatic Involvement during Immune Checkpoint Inhibition

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