Reporte de caso: diabetes mellitus tipo 1 inducida por pembrolizumab en un paciente con adenocarcinoma de pulmón

Presentamos el caso de una paciente sin comorbilidades metabólicas con diagnóstico de adenocarcinoma de pulmón en manejo con pembrolizumab, quien, posterior al tercer ciclo de tratamiento, debuta con cetoacidosis diabética, requiere manejo para crisis hiperglucémica e insulina. Se realizó diagnóstico de diabetes mellitus tipo 1 y se reintrodujo el tratamiento de pembrolizumab a 200 mg cada tres semanas además del manejo con insulina. En la actualidad la paciente permanece con una respuesta parcial posterior a 1 año del diagnóstico y sigue en manejo con insulinoterapia. En vista que en la actualidad no se cuenta con protocolos y guías de manejo para esta entidad, se realiza revisión del manejo y de la literatura debido a que solo se encuentran 6 casos reportados, siendo este el primer caso reportado en Colombia.

1. Cheema A, Makadia B, Karwadia T, Bajwa R, Hossain M. Autoimmune diabetes associated with pembrolizumab: A review of published case report. World J Oncol. 2018;9(1):1-4. doi: 10.14740/wjon1085w
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.

neoplasias pulmonares
cetoacidosis diabética
diabetes mellitus tipo 1
insulina
anticuerpos monoclonales humanizados (anti-PD-1)