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

被引：20

作者：

Grimmelmann, Imke ^{[1
]}

Momma, Michael ^{[2
]}

Zimmer, Lisa ^{[3
]}

Hassel, Jessica C. ^{[4
]}

Heinzerling, Lucie ^{[5
]}

Pfohler, Claudia ^{[6
]}

Loquai, Carmen ^{[7
]}

Ruini, Cristel ^{[8
]}

Utikal, Jochen ^{[9
,10
]}

Thoms, Kai-Martin ^{[11
]}

Kaehler, Katharina C. ^{[12
]}

Eigentler, Thomas ^{[13
]}

Herbst, Rudolf A. ^{[14
]}

Meier, Friedegund ^{[15
,16
,17
]}

Debus, Dirk ^{[18
]}

Berking, Carola ^{[5
]}

Kochanek, Corinna ^{[1
]}

Ugurel, Selma ^{[3
]}

Gutzmer, Ralf ^{[1
]}

机构：

[1] Hannover Med Sch, Skin Canc Ctr Hannover, Dept Dermatol, Carl Neuberg Str 1, D-30625 Hannover, Germany

[2] Diabet Ctr L1, Lohstr 1-2, D-31785 Hameln, Germany

[3] Univ Duisburg Essen, Dept Dermatol, Essen, Germany

[4] Univ Hosp Heidelberg, Natl Ctr Tumor Dis, Dept Dermatol, Neuenheimer Feld 460, D-69120 Heidelberg, Germany

[5] Friedrich Alexander Univ Erlangen Nurnberg, Univ Klinikum Erlangen, Comprehens Canc Ctr Erlangen European Metropolita, Dept Dermatol, Erlangen, Germany

[6] Saarland Univ, Med Sch, Homburg, Germany

[7] Univ Med Ctr Mainz, Dept Dermatol, Mainz, Germany

[8] Ludwig Maximilians Univ Munchen, Dept Dermatol, Univ Hosp, Munich, Germany

[9] German Canc Res Ctr, Skin Canc Unit, Heidelberg, Germany

[10] Ruprecht Karl Univ Heidelberg, Dept Dermatol Venereol & Allergol, Univ Med Ctr Goettingen, Mannheim, Germany

[11] Univ Med Ctr Goettingen, Dept Dermatol Venerol & Allergol, Gottingen, Germany

[12] Schleswig Holstein Univ Hosp, Skin Canc Ctr, Dept Dermatol, Campus Kiel, Kiel, Germany

[13] Univ Tubingen, Dept Dermatol, Tubingen, Germany

[14] Helios Klinikum Erfurt, Dept Dermatol, Erfurt, Germany

[15] Univ Canc Ctr Dresden, Skin Canc Ctr, Dresden, Germany

[16] Natl Ctr Tumor Dis, Dresden, Germany

[17] TU, Dept Dermatol, Univ Hosp Carl Gustav Carus, Dresden, Germany

[18] Paracelsus Med Univ, Nuremberg Gen Hosp, Dept Dermatol, Nurnberg, Germany

来源：

EUROPEAN JOURNAL OF CANCER | 2021年 / 149卷

关键词：

Nivolumab; Pembrolizumab; PD-1; inhibitor; Ipilimumab; Immune checkpoint inhibitors; Lipase; Diabetes; Pancreatitis; Diabetes mellitus; Immune-related adverse events; MANAGEMENT;

D O I：

10.1016/j.ejca.2021.02.017

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. (c) 2021 Elsevier Ltd. All rights reserved.

引用

页码：1 / 10

页数：10

共 20 条

[1] Characteristics and clinical course of type 1 diabetes mellitus related to anti-programmed cell death-1 therapy [J].

Baden, Megu Yamaguchi ;

Imagawa, Akihisa ;

Abiru, Norio ;

Awata, Takuya ;

Ikegami, Hiroshi ;

Uchigata, Yasuko ;

Oikawa, Yoichi ;

Osawa, Haruhiko ;

Kajio, Hiroshi ;

Kawasaki, Eiji ;

Kawabata, Yumiko ;

Kozawa, Junji ;

Shimada, Akira ;

Takahashi, Kazuma ;

Tanaka, Shoichiro ;

Chujo, Daisuke ;

Fukui, Tomoyasu ;

Miura, Junnosuke ;

Yasuda, Kazuki ;

Yasuda, Hisafumi ;

Kobayashi, Tetsuro ;

Hanafusa, Toshiaki ;

Nagafuchi, Seiho ;

Okamoto, Masahide ;

Ogawa, Osamu ;

Itateyama, Emi ;

Ohtake, Hiroyuki ;

Hirota, Yushi ;

Tomoyasu, Masako ;

Nakajima, Yasushi ;

Yano, Seiichi ;

Ashida, Kenji ;

Kumagai, Ryo ;

Yagyu, Hiroaki ;

Koriyama, Nobuyuki ;

Fukui, Michiaki ;

Daikoku, Harumi ;

Asai, Shiko ;

Mochida, Akihiro ;

Okajima, Fumitaka ;

Takagi, Satoshi ;

Nagasawa, Kaoru ;

Taketomo, Yasunori .

DIABETOLOGY INTERNATIONAL, 2019, 10 (01) :58-66

[2] Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination [J].

Boutros, Celine ;

Tarhini, Ahmad ;

Routier, Emilie ;

Lambotte, Olivier ;

Ladurie, Francois Leroy ;

Carbonnel, Franck ;

Izzeddine, Hassane ;

Marabelle, Aurelien ;

Champiat, Stephane ;

Berdelou, Armandine ;

Lanoy, Emilie ;

Texier, Matthieu ;

Libenciuc, Cristina ;

Eggermont, Alexander M. M. ;

Soria, Jean-Charles ;

Mateus, Christine ;

Robert, Caroline .

NATURE REVIEWS CLINICAL ONCOLOGY, 2016, 13 (08) :473-486

[3] Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline [J].

Brahmer, Julie R. ;

Lacchetti, Christina ;

Schneider, Bryan J. ;

Atkins, Michael B. ;

Brassil, Kelly J. ;

Caterino, Jeffrey M. ;

Chau, Ian ;

Ernstoff, Marc S. ;

Gardner, Jennifer M. ;

Ginex, Pamela ;

Hallmeyer, Sigrun ;

Chakrabarty, Jennifer Holter ;

Leighl, Natasha B. ;

Mammen, Jennifer S. ;

McDermott, David F. ;

Naing, Aung ;

Nastoupil, Loretta J. ;

Phillips, Tanyanika ;

Porter, Laura D. ;

Puzanov, Igor ;

Reichner, Cristina A. ;

Santomasso, Bianca D. ;

Seigel, Carole ;

Spira, Alexander ;

Suarez-Almazor, Maria E. ;

Wang, Yinghong ;

Weber, Jeffrey S. ;

Wolchok, Jedd D. ;

Thompson, John A. .

JOURNAL OF CLINICAL ONCOLOGY, 2018, 36 (17) :1714-+

[4] Immune checkpoint inhibitors and type 1 diabetes mellitus: a case report and systematic review [J].

de Filette, Jeroen M. K. ;

Pent, Joeri J. ;

Decoster, Lore ;

Vissers, Thomas ;

Bravenboer, Bert ;

Van der Auwera, Bart J. ;

Goruss, Frans K. ;

Roep, Bart O. ;

Aspeslagh, Sandrine ;

Neyns, Bart ;

Velkeniers, Brigitte ;

Kharagjitsingh, Aan, V .

EUROPEAN JOURNAL OF ENDOCRINOLOGY, 2019, 181 (03) :363-374

[5] Diagnosis, monitoring and management of immune-related adverse drug reactions of anti-PD-1 antibody therapy [J].

Eigentler, Thomas K. ;

Hassel, Jessica C. ;

Berking, Carola ;

Aberle, Jens ;

Bachmann, Oliver ;

Gruenwald, Viktor ;

Kaehler, Katharina C. ;

Loquai, Carmen ;

Reinmuth, Niels ;

Steins, Martin ;

Zimmer, Lisa ;

Sendl, Anna ;

Gutzmer, Ralf .

CANCER TREATMENT REVIEWS, 2016, 45 :7-18

[6] New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1) [J].

Eisenhauer, E. A. ;

Therasse, P. ;

Bogaerts, J. ;

Schwartz, L. H. ;

Sargent, D. ;

Ford, R. ;

Dancey, J. ;

Arbuck, S. ;

Gwyther, S. ;

Mooney, M. ;

Rubinstein, L. ;

Shankar, L. ;

Dodd, L. ;

Kaplan, R. ;

Lacombe, D. ;

Verweij, J. .

EUROPEAN JOURNAL OF CANCER, 2009, 45 (02) :228-247

[7] Clinical Significance of Pancreatic Atrophy Induced by Immune-Checkpoint Inhibitors: A Case-Control Study [J].

Eshet, Yael ;

Baruch, Erez Nissim ;

Shapira-Frommer, Ronnie ;

Steinberg-Silman, Yael ;

Kuznetsov, Teodor ;

Ben-Betzalel, Guy ;

Daher, Sameh ;

Gluck, Iris ;

Asher, Nethanel ;

Apter, Sara ;

Schachter, Jacob ;

Bar, Jair ;

Boursi, Ben ;

Markel, Gal .

CANCER IMMUNOLOGY RESEARCH, 2018, 6 (12) :1453-1458

[8] Thinking Critically About Classifying Adverse Events: Incidence of Pancreatitis in Patients Treated With Nivolumab plus Ipilimumab [J].

Friedman, Claire F. ;

Clark, Varina ;

Raikhel, Andrew V. ;

Barz, Tim ;

Shoushtari, Alexander N. ;

Momtaz, Parisa ;

Callahan, Margaret K. ;

Wolchok, Jedd D. ;

Chapman, Paul B. ;

Hellmann, Matthew D. ;

Postow, Michael A. .

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2017, 109 (04)

[9] Day-to-day variations of serum pancreatic enzymes in benign pancreatic hyperenzymemia [J].

Gullo, Lucio .

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY, 2007, 5 (01) :70-74

[10] Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (vol 28, pg 119, 2017) [J].

Haanen, J. B. A. G. ;

Carbonnel, F. ;

Robert, C. ;

Kerr, K. M. ;

Peters, S. ;

Larkin, J. ;

Jordan, K. .

ANNALS OF ONCOLOGY, 2018, 29 :264-266

← 1 2 →