Keywords
Lung neoplasms
Diabetic ketoacidosis
Diabetes mellitus type 1
Insulin
Humanized Monoclonal Antibodies (anti-PD-1)
Diabetic ketoacidosis
Diabetes mellitus type 1
Insulin
Humanized Monoclonal Antibodies (anti-PD-1)
How to Cite
Bedoya-Trujillo, L. N., & Bedoya-Trujillo, P. N. (2021). Case report: pembrolizumab-induced Type 1 diabetes mellitus in a patient with lung adenocarcinoma. Revista Colombiana De Endocrinología, Diabetes &Amp; Metabolismo, 7(3), 188–192. https://doi.org/10.53853/encr.7.3.632
Abstract
We present a female patient without metabolic comorbidities, diagnosed with lung adenocarcinoma, in management with pembrolizumab after the third course of treatment, debuted with diabetic ketoacidosis, requiring management for hyperglycemic crisis and insulin needed. Diabetes mellitus type 1 is diagnosed, to get control of this metabolic complication infrequent in immunotherapy, it is decided to reintroduce pembrolizumab treatment at 200 mg every three weeks in addition to insulin management. At present the patient remains with a partial response after 1 year of diagnosis and continues to be managed with insulin therapy. Given that currently there are no protocols and management guidelines for this entity, a review of the management and the literature is carried out because only 6 reported cases are found, this being the first case reported in Colombia.
References
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5. Gaudy C, Clevy C, Monestier S, Dubois N, Preau Y, Mallet S, et al. Anti-PD1 pembrolizumab can induce exceptional fulminant type 1 diabetes. Diabetes Care. 2015;38(11):e182-3. doi: 10.2337/dc15-1331
6. Maamari, J., Yeung, S. C. J., & Chaftari, P. S. (2019). Diabetic ketoacidosis induced by a single dose of pembrolizumab. The American journal of emergency medicine, 37(2), 376-e1.
7. Ansari MJ, Salama AD, Chitnis T, Smith RN, Yagita H, Akiba H, et al. The programmed death-1 (PD-1) pathway regulates autoimmune diabetes in nonobese diabetic (NOD) mice. J Exp Med. 2003;198(1):63-9. doi: 10.1084/ jem.20022125
8. Chae YK, Chiec L, Mohindra N, Gentzler R, Patel J, Giles F. A case of pembrolizumab-induced type-1 diabetes mellitus and discussion of immune checkpoint inhibitor-induced type 1 diabetes. Cancer Immunol Immunother. 2017;66(1):25-32. doi: 10.1007/s00262-016-1913-7.
9. Aleksova J, Lau P, Soldatos G, McArthur G. Glucocorticoids did not reverse type 1 diabetes mellitus secondary to pembrolizumab in a patient with metastatic melanoma. BMJ Case Rep. 2016;2016:bcr2016217454. doi: 10,11135/bcr-2016-217454
10. Hansen E, Sahasrabudhe D, Sievert L. A case report of insulin-dependent diabetes as immune-related toxicity of pembrolizumab: presentation, management and outcome. Cancer Immunol Immunother. 2016;65(6):765-7. doi: 10.1007/s00262-016-1835-4
11. Sanlorenzo M, Vujic I, Daud A, Algazi A, Gubens M, Alcántara S, et al. Pembrolizumab Cutaneous Adverse Events and Their Association With Disease Progression. JAMA. 2015;151(11):1206-12. doi: 10.1001/jamadermatol.2015.1916
12. Baxi S, Yang A, Gennarelli R, Khan N, Wang Z, Boyce L, et al. Immune-related adverse events for anti-PD-1 and anti-PD-L1 drugs: systematic review and meta-analysis. BMJ. 2018;360:k793. doi: 10.1136/bmj.k793
13. Shamy T, Aguasvivas M, Serhan M, Fojas M. Diabetic Ketoacidosis Triggered by Pembrolizumab in a Patient with Bladder Cancer. Diabetes. 2018;67(Supplement 1). doi: 10.2337/db18-219-LB
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15. Alarcon-Casas L, VargasR, Batacchi Z, Hirsch I. Progression to insulin dependence post-treatment with immune checkpoint inhibitors in pre-existing type 2 diabetes. AACE Clin Case Rep. 2017;3(2):e153-7.
16. Wang P, Chen Y, Song S, Wang t, Ji W, Li S, et al. Immune-Related Adverse Events Associated with Anti-PD-1/PD-L1 Treatment for Malignancies: A Meta-Analysis. Front Pharmacol. 2017;8:730. doi: 10.3389/ fphar.2017.00730
17. Kapke J, Shaheen Z, Kilari D, Knudson P, Wong S. Immune Checkpoint Inhibitor-Associated Type 1 Diabetes mellitus: Case Series, Review of the Literature, and Optimal Management. Case Rep Oncol. 2017;10(3):897- 909. doi: 10.1159/000480634.
18. Humayun MA, Poole R. A case of multiple immune toxicities from Ipilimumab and pembrolizumab treatment. Hormones. 2016;15(2):303-6.
19. Hughes J, Vudattu N, Sznol M, Gettinger S, Kluger H, Lupsa B, et al. Precipitation of autoimmune diabetes with anti-PD-1 immunotherapy. Diabetes Care. 2015;38(4):e55-e57. doi: 10.2337/dc14-2349
20. Martin-Liberal J, Furness AJ, Joshi K, Peggs KS, Quezada SA, Larkin J. Antiprogrammed cell death-1 therapy and insulin-dependent diabetes: a case report. Cancer Immunology, Immunotherapy. 2015;64(6):765-7.
2. Abdel-Wahab N, Shah M, Suarez-Almazor ME. Adverse events associated with immune checkpoint blockade in patients with cancer: a systematic review of case reports. PLoS One. 2016;11(7):e0160221. doi: 10.1371/ journal.pone.0160221
3. Faghfuri E, Faramarzi MA, Nikfar S, Abdollahi M. Nivolumab and pembrolizumab as immune-modulating monoclonal antibodies targeting the PD-1 receptor to treat melanoma. Expert Rev Anticancer Ther. 2015;15(9):981- 93. doi: 10.1586/14737140.2015.1074862
4. Smith-Cohn, M. A., Gill, D., Voorhies, B. N., Agarwal, N., & Garrido-Laguna, I. (2017). Case report: pembrolizumab-induced Type 1 diabetes in a patient with metastatic cholangiocarcinoma. Immunotherapy, 9(10), 797-804.
5. Gaudy C, Clevy C, Monestier S, Dubois N, Preau Y, Mallet S, et al. Anti-PD1 pembrolizumab can induce exceptional fulminant type 1 diabetes. Diabetes Care. 2015;38(11):e182-3. doi: 10.2337/dc15-1331
6. Maamari, J., Yeung, S. C. J., & Chaftari, P. S. (2019). Diabetic ketoacidosis induced by a single dose of pembrolizumab. The American journal of emergency medicine, 37(2), 376-e1.
7. Ansari MJ, Salama AD, Chitnis T, Smith RN, Yagita H, Akiba H, et al. The programmed death-1 (PD-1) pathway regulates autoimmune diabetes in nonobese diabetic (NOD) mice. J Exp Med. 2003;198(1):63-9. doi: 10.1084/ jem.20022125
8. Chae YK, Chiec L, Mohindra N, Gentzler R, Patel J, Giles F. A case of pembrolizumab-induced type-1 diabetes mellitus and discussion of immune checkpoint inhibitor-induced type 1 diabetes. Cancer Immunol Immunother. 2017;66(1):25-32. doi: 10.1007/s00262-016-1913-7.
9. Aleksova J, Lau P, Soldatos G, McArthur G. Glucocorticoids did not reverse type 1 diabetes mellitus secondary to pembrolizumab in a patient with metastatic melanoma. BMJ Case Rep. 2016;2016:bcr2016217454. doi: 10,11135/bcr-2016-217454
10. Hansen E, Sahasrabudhe D, Sievert L. A case report of insulin-dependent diabetes as immune-related toxicity of pembrolizumab: presentation, management and outcome. Cancer Immunol Immunother. 2016;65(6):765-7. doi: 10.1007/s00262-016-1835-4
11. Sanlorenzo M, Vujic I, Daud A, Algazi A, Gubens M, Alcántara S, et al. Pembrolizumab Cutaneous Adverse Events and Their Association With Disease Progression. JAMA. 2015;151(11):1206-12. doi: 10.1001/jamadermatol.2015.1916
12. Baxi S, Yang A, Gennarelli R, Khan N, Wang Z, Boyce L, et al. Immune-related adverse events for anti-PD-1 and anti-PD-L1 drugs: systematic review and meta-analysis. BMJ. 2018;360:k793. doi: 10.1136/bmj.k793
13. Shamy T, Aguasvivas M, Serhan M, Fojas M. Diabetic Ketoacidosis Triggered by Pembrolizumab in a Patient with Bladder Cancer. Diabetes. 2018;67(Supplement 1). doi: 10.2337/db18-219-LB
14. Manrique C, Silva D. Pancreatic beta cells apoptosis in type 1 diabetes. Rev Fac Med. 2006;54(3):181-90.
15. Alarcon-Casas L, VargasR, Batacchi Z, Hirsch I. Progression to insulin dependence post-treatment with immune checkpoint inhibitors in pre-existing type 2 diabetes. AACE Clin Case Rep. 2017;3(2):e153-7.
16. Wang P, Chen Y, Song S, Wang t, Ji W, Li S, et al. Immune-Related Adverse Events Associated with Anti-PD-1/PD-L1 Treatment for Malignancies: A Meta-Analysis. Front Pharmacol. 2017;8:730. doi: 10.3389/ fphar.2017.00730
17. Kapke J, Shaheen Z, Kilari D, Knudson P, Wong S. Immune Checkpoint Inhibitor-Associated Type 1 Diabetes mellitus: Case Series, Review of the Literature, and Optimal Management. Case Rep Oncol. 2017;10(3):897- 909. doi: 10.1159/000480634.
18. Humayun MA, Poole R. A case of multiple immune toxicities from Ipilimumab and pembrolizumab treatment. Hormones. 2016;15(2):303-6.
19. Hughes J, Vudattu N, Sznol M, Gettinger S, Kluger H, Lupsa B, et al. Precipitation of autoimmune diabetes with anti-PD-1 immunotherapy. Diabetes Care. 2015;38(4):e55-e57. doi: 10.2337/dc14-2349
20. Martin-Liberal J, Furness AJ, Joshi K, Peggs KS, Quezada SA, Larkin J. Antiprogrammed cell death-1 therapy and insulin-dependent diabetes: a case report. Cancer Immunology, Immunotherapy. 2015;64(6):765-7.
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