Imke Grimmelmann1, Michael Momma2, Lisa Zimmer3, Jessica C Hassel4, Lucie Heinzerling5, Claudia Pföhler6, Carmen Loquai7, Cristel Ruini8, Jochen Utikal9, Kai-Martin Thoms10, Katharina C Kähler11, Thomas Eigentler12, Rudolf A Herbst13, Friedegund Meier14, Dirk Debus15, Carola Berking16, Corinna Kochanek17, Selma Ugurel18, Ralf Gutzmer19. 1. Skin Cancer Center Hannover, Department of Dermatology, Hannover Medical School, Carl Neuberg Str. 1, 30625, Hannover, Germany. Electronic address: Grimmelmann.Imke@mh-hannover.de. 2. Diabetes Center L1, Lohstrasse 1-2, 31785, Hameln, Germany. Electronic address: m.momma@diabeteszentrum-l1.de. 3. Department of Dermatology, University of Duisburg-Essen, Essen, Germany. Electronic address: lisa.zimmer@uk-essen.de. 4. Department of Dermatology, National Center for Tumor Diseases, University Hospital Heidelberg, Im Neuenheimer Feld 460, 69120, Heidelberg, Germany. Electronic address: Jessica.hassel@med.uni-heidelberg.de. 5. Department of Dermatology, Universitätsklinikum Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Comprehensive Cancer Center Erlangen - European Metropolitan Region of Nuremberg, Germany. Electronic address: lucie.heinzerling@uk-erlangen.de. 6. Saarland University Medical School, Homburg, Germany. Electronic address: Claudia.pfoehler@uks.eu. 7. Department of Dermatology, University Medical Center Mainz, Mainz, Germany. Electronic address: carmen.loquai@unimedizin-mainz.de. 8. Department of Dermatology, University Hospital, LMU Munich, Munich, Germany. Electronic address: Cristel.Ruini@med.uni-muenchen.de. 9. Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany. Electronic address: jochen.utikal@umm.de. 10. Department of Dermatology, Venerology and Allergology, University Medical Center Goettingen, Goettingen, Germany. Electronic address: kai.thoms@med.uni-goettingen.de. 11. Department of Dermatology, Skin Cancer Center, Schleswig-Holstein University Hospital, Campus Kiel, Kiel, Germany. Electronic address: kkaehler@dermatology.uni-kiel.de. 12. Department of Dermatology, University Tübingen, Tübingen, Germany. Electronic address: thomas.eigentler@live.com. 13. Department of Dermatology, Helios Klinikum Erfurt, Erfurt, Germany. Electronic address: rudolf.herbst@helios-gesundheit.de. 14. Skin Cancer Center at the University Cancer Centre Dresden and National Center for Tumor Diseases, Dresden, Germany; Department of Dermatology, University Hospital Carl Gustav Carus, TU, Dresden, Germany. Electronic address: Friedegund.meier@uniklinikum-dresden.de. 15. Department of Dermatology, Nuremberg General Hospital, Paracelsus Medical University, Nuremberg, Germany. Electronic address: Dirk.Debus@klinikum-nuernberg.de. 16. Department of Dermatology, Universitätsklinikum Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Comprehensive Cancer Center Erlangen - European Metropolitan Region of Nuremberg, Germany. Electronic address: Carola.Berking@uk-erlangen.de. 17. Skin Cancer Center Hannover, Department of Dermatology, Hannover Medical School, Carl Neuberg Str. 1, 30625, Hannover, Germany. 18. Department of Dermatology, University of Duisburg-Essen, Essen, Germany. Electronic address: selma.ugurel@uk-essen.de. 19. Skin Cancer Center Hannover, Department of Dermatology, Hannover Medical School, Carl Neuberg Str. 1, 30625, Hannover, Germany. Electronic address: Gutzmer.ralf@mh-hannover.de.
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.
AIM: Immune checkpoint inhibition (ICI) triggers immune-related adverse events (irAEs). The relevance of lipase elevation remains unclear. PATIENTS AND METHODS: Skin cancerpatients 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.