Abstract

Case Report

Clinical Approach to Immunotherapy-induced Type 1 Diabetes Mellitus: A Case of Pembrolizumab Associated Insulin-dependent Diabetes in a Patient with NSCLC

Nikolaos Ntertsos, George Christantoniou, Krystallia Kyrka, Persefoni Pezirkianidou, Vasileios Bikos, Papadaki Konstantina and Theodora Tsiouda*

Published: 25 September, 2023 | Volume 7 - Issue 2 | Pages: 024-027

As the introduction of immune checkpoint inhibitors in the treatment of various cancers is now proven to be already acquired knowledge, so does a new challenge arise for clinicians; the understanding, diagnosis, and management of the rarest adverse effects of immunotherapy. We present a case of type-1 diabetes Mellitus (T1DM) in a patient with non-small cell lung carcinoma (NSCLC) treated with pembrolizumab. Following ten cycles of treatment, our patient was diagnosed with T1DM after being admitted for diabetic ketoacidosis and stayed hospitalized in the ICU. Later, they continued treatment with insulin, having shown disease response to pembrolizumab, and resumed immunotherapy while on insulin. Immunotherapy-induced T1DM can sometimes occur with PD1/PD-L1 blockage therapies. It has a rapid onset, is characterized by insulin deficiency due to the autoimmune destruction of beta-cells, and usually presents itself with diabetic ketoacidosis. Unlike most of the other adverse effects of immunotherapy, glucocorticoids don’t seem to be of therapeutic value, and insulin substitution is required. Regular glucose monitoring can be key to early diagnosis and prevention of hospitalization. 

Read Full Article HTML DOI: 10.29328/journal.jprr.1001047 Cite this Article Read Full Article PDF

Keywords:

Immunotherapy; Pembrolizumab; Type 1 diabetes mellitus; Non-small cell lung cancer; Insulin; Diabetic ketoacidosis

References

  1. Alsaab HO, Sau S, Alzhrani R, Tatiparti K, Bhise K, Kashaw SK, Iyer AK. PD-1 and PD-L1 Checkpoint Signaling Inhibition for Cancer Immunotherapy: Mechanism, Combinations, and Clinical Outcome. Front Pharmacol. 2017 Aug 23;8:561. doi: 10.3389/fphar.2017.00561. PMID: 28878676; PMCID: PMC5572324.
  2. Liu J, Chen Z, Li Y, Zhao W, Wu J, Zhang Z. PD-1/PD-L1 Checkpoint Inhibitors in Tumor Immunotherapy. Front Pharmacol. 2021 Sep 1;12:731798. doi: 10.3389/fphar.2021.731798. PMID: 34539412; PMCID: PMC8440961.
  3. Olszanski AJ. Principles of immunotherapy. J Natl Compr Canc Netw. 2015 May;13(5 Suppl):670-2. doi: 10.6004/jnccn.2015.0199. PMID: 25995426.
  4. Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O, Bhatia S, Martins R, Eaton K, Chen S, Salay TM, Alaparthy S, Grosso JF, Korman AJ, Parker SM, Agrawal S, Goldberg SM, Pardoll DM, Gupta A, Wigginton JM. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012 Jun 28;366(26):2455-65. doi: 10.1056/NEJMoa1200694. Epub 2012 Jun 2. PMID: 22658128; PMCID: PMC3563263.
  5. Barroso-Sousa R, Barry WT, Garrido-Castro AC, Hodi FS, Min L, Krop IE, Tolaney SM. Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis. JAMA Oncol. 2018 Feb 1;4(2):173-182. doi: 10.1001/jamaoncol.2017.3064. PMID: 28973656; PMCID: PMC5838579.
  6. Tsang VHM, McGrath RT, Clifton-Bligh RJ, Scolyer RA, Jakrot V, Guminski AD, Long GV, Menzies AM. Checkpoint Inhibitor-Associated Autoimmune Diabetes Is Distinct From Type 1 Diabetes. J Clin Endocrinol Metab. 2019 Nov 1;104(11):5499-5506. doi: 10.1210/jc.2019-00423. PMID: 31265074.
  7. Stamatouli AM, Quandt Z, Perdigoto AL, Clark PL, Kluger H, Weiss SA, Gettinger S, Sznol M, Young A, Rushakoff R, Lee J, Bluestone JA, Anderson M, Herold KC. Collateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors. Diabetes. 2018 Aug;67(8):1471-1480. doi: 10.2337/dbi18-0002. Epub 2018 Jun 24. PMID: 29937434; PMCID: PMC6054443.
  8. https://cdn-links.lww.com/permalink/cm9/a/cm9_2020_06_08_cai_cmj-2020-382_sdc2.pdf
  9. Imagawa A, Hanafusa T, Miyagawa J, Matsuzawa Y. A novel subtype of type 1 diabetes mellitus characterized by a rapid onset and an absence of diabetes-related antibodies. Osaka IDDM Study Group. N Engl J Med. 2000 Feb 3;342(5):301-7. doi: 10.1056/NEJM200002033420501. PMID: 10655528.
  10. Clotman K, Janssens K, Specenier P, Weets I, De Block CEM. Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. J Clin Endocrinol Metab. 2018 Sep 1;103(9):3144-3154. doi: 10.1210/jc.2018-00728. PMID: 29955867.
  11. Aleksova J, Lau PK, 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 Nov 23;2016:bcr2016217454. doi: 10.1136/bcr-2016-217454. PMID: 27881588; PMCID: PMC5174822.
  12. Smati S, Buffier P, Bouillet B, Archambeaud F, Vergès B, Cariou B. Expert opinion on immunotherapy induced diabetes. Ann Endocrinol (Paris). 2018 Oct;79(5):545-549. doi: 10.1016/j.ando.2018.07.006. Epub 2018 Jul 25. PMID: 30126628.

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