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

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

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Vydané v:	European journal of cancer (1990) Ročník 149; s. 1 - 10
Hlavní autori:	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
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	England Elsevier Ltd 01.05.2021 Elsevier Science Ltd
Predmet:	Blood Cancer Colitis Diabetes Diabetes mellitus Diabetes mellitus (insulin dependent) Diabetic ketoacidosis Glucose Immune checkpoint inhibitors Immune-related adverse events Ipilimumab Ketoacidosis Lipase Nivolumab Pancreas Pancreatitis PD-1 inhibitor Pembrolizumab Signs and symptoms Skin cancer Thyroiditis Pembrolizumab Immune-related adverse events Nivolumab Ipilimumab Diabetes mellitus Pancreatitis Immune checkpoint inhibitors PD-1 inhibitor Diabetes Lipase
ISSN:	0959-8049, 1879-0852, 1879-0852
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Abstract	Immune checkpoint inhibition (ICI) triggers immune-related adverse events (irAEs). The relevance of lipase elevation remains unclear. 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. 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. 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. •Lipase elevation is often associated with e.g. colitis but not pancreatitis.•Immune checkpoint inhibition diabetes occurs often with endocrine immune-related adverse event and in 50% with lipase elevation.•Lipase elevation shortly precedes the onset of type I diabetes mellitus.•Therefore, blood glucose but not lipase monitoring is recommended.
AbstractList	Immune checkpoint inhibition (ICI) triggers immune-related adverse events (irAEs). The relevance of lipase elevation remains unclear.AIMImmune checkpoint inhibition (ICI) triggers immune-related adverse events (irAEs). The relevance of lipase elevation remains unclear.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.PATIENTS AND METHODSSkin 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.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.RESULTSWe 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.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.CONCLUSIONIncreased 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. Immune checkpoint inhibition (ICI) triggers immune-related adverse events (irAEs). The relevance of lipase elevation remains unclear. 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. 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. 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. •Lipase elevation is often associated with e.g. colitis but not pancreatitis.•Immune checkpoint inhibition diabetes occurs often with endocrine immune-related adverse event and in 50% with lipase elevation.•Lipase elevation shortly precedes the onset of type I diabetes mellitus.•Therefore, blood glucose but not lipase monitoring is recommended. 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. Immune checkpoint inhibition (ICI) triggers immune-related adverse events (irAEs). The relevance of lipase elevation remains unclear. 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. 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. 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.
Author	Meier, Friedegund Berking, Carola Momma, Michael Kochanek, Corinna Gutzmer, Ralf Pföhler, Claudia Ugurel, Selma Utikal, Jochen Thoms, Kai-Martin Debus, Dirk Hassel, Jessica C. Ruini, Cristel Heinzerling, Lucie Herbst, Rudolf A. Eigentler, Thomas Kähler, Katharina C. Zimmer, Lisa Grimmelmann, Imke Loquai, Carmen
Author_xml	– sequence: 1 givenname: Imke surname: Grimmelmann fullname: Grimmelmann, Imke email: Grimmelmann.Imke@mh-hannover.de organization: Skin Cancer Center Hannover, Department of Dermatology, Hannover Medical School, Carl Neuberg Str. 1, 30625, Hannover, Germany – sequence: 2 givenname: Michael surname: Momma fullname: Momma, Michael email: m.momma@diabeteszentrum-l1.de organization: Diabetes Center L1, Lohstrasse 1-2, 31785, Hameln, Germany – sequence: 3 givenname: Lisa orcidid: 0000-0002-3680-3521 surname: Zimmer fullname: Zimmer, Lisa email: lisa.zimmer@uk-essen.de organization: Department of Dermatology, University of Duisburg-Essen, Essen, Germany – sequence: 4 givenname: Jessica C. surname: Hassel fullname: Hassel, Jessica C. email: Jessica.hassel@med.uni-heidelberg.de organization: Department of Dermatology, National Center for Tumor Diseases, University Hospital Heidelberg, Im Neuenheimer Feld 460, 69120, Heidelberg, Germany – sequence: 5 givenname: Lucie surname: Heinzerling fullname: Heinzerling, Lucie email: lucie.heinzerling@uk-erlangen.de organization: Department of Dermatology, Universitätsklinikum Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Comprehensive Cancer Center Erlangen - European Metropolitan Region of Nuremberg, Germany – sequence: 6 givenname: Claudia surname: Pföhler fullname: Pföhler, Claudia email: Claudia.pfoehler@uks.eu organization: Saarland University Medical School, Homburg, Germany – sequence: 7 givenname: Carmen surname: Loquai fullname: Loquai, Carmen email: carmen.loquai@unimedizin-mainz.de organization: Department of Dermatology, University Medical Center Mainz, Mainz, Germany – sequence: 8 givenname: Cristel orcidid: 0000-0002-9860-1095 surname: Ruini fullname: Ruini, Cristel email: Cristel.Ruini@med.uni-muenchen.de organization: Department of Dermatology, University Hospital, LMU Munich, Munich, Germany – sequence: 9 givenname: Jochen surname: Utikal fullname: Utikal, Jochen email: jochen.utikal@umm.de organization: Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany – sequence: 10 givenname: Kai-Martin surname: Thoms fullname: Thoms, Kai-Martin email: kai.thoms@med.uni-goettingen.de organization: Department of Dermatology, Venerology and Allergology, University Medical Center Goettingen, Goettingen, Germany – sequence: 11 givenname: Katharina C. surname: Kähler fullname: Kähler, Katharina C. email: kkaehler@dermatology.uni-kiel.de organization: Department of Dermatology, Skin Cancer Center, Schleswig-Holstein University Hospital, Campus Kiel, Kiel, Germany – sequence: 12 givenname: Thomas orcidid: 0000-0003-0019-2770 surname: Eigentler fullname: Eigentler, Thomas email: thomas.eigentler@live.com organization: Department of Dermatology, University Tübingen, Tübingen, Germany – sequence: 13 givenname: Rudolf A. surname: Herbst fullname: Herbst, Rudolf A. email: rudolf.herbst@helios-gesundheit.de organization: Department of Dermatology, Helios Klinikum Erfurt, Erfurt, Germany – sequence: 14 givenname: Friedegund surname: Meier fullname: Meier, Friedegund email: Friedegund.meier@uniklinikum-dresden.de organization: Skin Cancer Center at the University Cancer Centre Dresden and National Center for Tumor Diseases, Dresden, Germany – sequence: 15 givenname: Dirk surname: Debus fullname: Debus, Dirk email: Dirk.Debus@klinikum-nuernberg.de organization: Department of Dermatology, Nuremberg General Hospital, Paracelsus Medical University, Nuremberg, Germany – sequence: 16 givenname: Carola orcidid: 0000-0003-0229-8931 surname: Berking fullname: Berking, Carola email: Carola.Berking@uk-erlangen.de organization: Department of Dermatology, Universitätsklinikum Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Comprehensive Cancer Center Erlangen - European Metropolitan Region of Nuremberg, Germany – sequence: 17 givenname: Corinna surname: Kochanek fullname: Kochanek, Corinna organization: Skin Cancer Center Hannover, Department of Dermatology, Hannover Medical School, Carl Neuberg Str. 1, 30625, Hannover, Germany – sequence: 18 givenname: Selma surname: Ugurel fullname: Ugurel, Selma email: selma.ugurel@uk-essen.de organization: Department of Dermatology, University of Duisburg-Essen, Essen, Germany – sequence: 19 givenname: Ralf orcidid: 0000-0001-7921-2820 surname: Gutzmer fullname: Gutzmer, Ralf email: Gutzmer.ralf@mh-hannover.de organization: Skin Cancer Center Hannover, Department of Dermatology, Hannover Medical School, Carl Neuberg Str. 1, 30625, Hannover, Germany
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Keywords	Pembrolizumab Immune-related adverse events Nivolumab Ipilimumab Diabetes mellitus Pancreatitis Immune checkpoint inhibitors PD-1 inhibitor Diabetes Lipase
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Snippet	Immune checkpoint inhibition (ICI) triggers immune-related adverse events (irAEs). The relevance of lipase elevation remains unclear. Skin cancer patients with... Aim Immune checkpoint inhibition (ICI) triggers immune-related adverse events (irAEs). The relevance of lipase elevation remains unclear. Patients and methods... Immune checkpoint inhibition (ICI) triggers immune-related adverse events (irAEs). The relevance of lipase elevation remains unclear.AIMImmune checkpoint...
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SubjectTerms	Blood Cancer Colitis Diabetes Diabetes mellitus Diabetes mellitus (insulin dependent) Diabetic ketoacidosis Glucose Immune checkpoint inhibitors Immune-related adverse events Ipilimumab Ketoacidosis Lipase Nivolumab Pancreas Pancreatitis PD-1 inhibitor Pembrolizumab Signs and symptoms Skin cancer Thyroiditis
Title	Lipase elevation and type 1 diabetes mellitus related to immune checkpoint inhibitor therapy – A multicentre study of 90 patients from the German Dermatooncology Group
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