Pembrolizumab is an effective anticancer immunotherapy. It is generally well tolerated although immune-related adverse events can occur. Autoimmune thyroid dysfunction is the most common one among these events. Several evidences suggested that pembrolizumab can induce thyroid dysfunction after several treatment cycles. The aim of the study is to evaluate the incidence and risk factors of thyroid function abnormalities related to pembrolizumab therapy. This is a multicenter prospective study including 100 patients with different cancers who initiated pembrolizumab treatment. Demographic data was collected in addition to the number of treatment cycles, history of thyroid surgery, thyroid disease, chemotherapy and steroid treatment. Baseline T3, T4 and TSH were measured and assessed periodically. Patients were distributed into 2 groups, those who maintained euthyroid state and the others who developed thyroid dysfunction. Assessment was analyzed looking for any relationship of this dysfunction with age, gender, dose, underlying diagnosis or previous disease or treatment lines. Thyroid dysfunction was reported in 31 patients (31%). Female patients were the predominant affected group, (P <0.001). Intriguingly, 38.75% of patients with euthyroidism were ex/current smokers compared with 19.35% of patients with thyroid dysfunction (P <0.028). The median number of pembrolizumab cycles in patients with euthyroidism and with thyroid dysfunction was 5.0 and 6.5, respectively (P <0.028). Finally, the presence of thyroid disease was more frequent among patients with thyroid dysfunction than those with euthyroidism (P <0.005). Conclusions: A considerable proportion of patients receiving pembrolizumab can develop thyroid dysfunction. Female gender, number of treatment cycles and history of thyroid disease may be risk factors for thyroid dysfunction in those patients. |
REFERENCES:
- Iwai Y, Hamanishi J, Chamoto K, et al. Cancer immunotherapies targeting the PD-1 signaling pathway. Biomed. Sci. 2017;24:26.
- Ferrari SM, Fallahi P, Galetta F, et al. Thyroid disorders induced by checkpoint inhibitors. Rev Endocr Metab Disord. 2018;19:325–33.
- Kassi E, Angelousi A, Asonitis N, et al. Endocrine-related adverse events associated with immune-checkpoint inhibitors in patients with melanoma. Cancer Med. 2019; 8:6585-94.
- Latif MF, Abdelgadir E, Omara M, Rashid F, Tirmazy SH, Khan F, et al. Immune checkpoint inhibitors-induced thyroid dysfunction in patients with advanced malignancies. Middle East J Cancer. 2022;13:616-23. doi: 10.30476/mejc.2022. 89620.1538.
- Chalan P, Di Dalmazi G, Pani F, et al. P. Thyroid dysfunctions secondary to cancer immunotherapy. J. Endocrinol Invest. 2018; 41:625–38.
- Barroso-Sousa R. Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis. JAMAONCOL. 2018;4:173–82.
- Lee H, Hodi FS, Giobbie-Hurder A. Characterization of Thyroid Disorders in Patients Receiving Immune Checkpoint Inhibition Therapy. Cancer Immunol Res. 2017;5:1133–40.
- De Filette J, Jansen Y, Schreuer M. Incidence of Thyroid-Related Adverse Events in Melanoma Patients Treated With Pembrolizumab. J Clin Endocrinol Metab. 2016;101:4431–39.
- Ruggeri RM, Campennì A, Giuffrida G, et al. Endocrine and metabolic adverse effects of immune checkpoint inhibitors: an overview (what endocrinologists should know). J Endocrinol Invest. 2019;42 :745–56.
-
- Brahmer JR, Lacchetti C, Schneider BJ. Management of Immune-Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2018;36:1714–68.
- Angell TE, Min L, Wieczorek TJ, Hodi FS. Unique cytologic features of thyroiditis caused by immune checkpoint inhibitor therapy for malignant melanoma. Genes Dis. 2018;5:46–48.
- Yoon JH, Hong AR, Kim HK, Kang HC. Characteristics of Immune-Related Thyroid Adverse Events in Patients Treated with PD-1/PD-L1 Inhibitors. Endocrinol Metab (Seoul). 2021;36:413-23. doi: 10.3803/EnM.2020.906. Epub 2021 Apr 6. PMID: 33820396; PMCID: PMC8090457.
- Morganstein DL, Lai Z, Spain L, et al. Thyroid abnormalities following the use of cytotoxic T-lymphocyte antigen-4 and programmed death receptor protein-1 inhibitors in the treatment of melanoma. Clin Endocrinol (Oxf) 2017;86: 614-20.
- Sakakida T, Ishikawa T, Uchino J, et al. Clinical features of immune-related thyroid dysfunction and its association with outcomes in patients with advanced malignancies treated by PD-1 blockade. Oncol Lett. 2019; 18:2140-47.
- Delivanis DA, Gustafson MP, Bornschlegl S, et al. Pembrolizumab-Induced Thyroiditis: Comprehensive Clinical Review and Insights into Underlying Involved Mechanisms. J Clin Endocrinol Metab. 2017 Aug 1; 102:2770-80.
- Osorio JC, Ni A, Chaft JE, et al. Antibody-mediated thyroid dysfunction during T-cell checkpoint blockade in patients with non-small-cell lung cancer. Ann Oncol. 2017; 28:583–89.
- Ribas A, Puzanov I, Dummer R, et al. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Lancet Oncol. 2015;16:908–18.
- Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015; 372:2018–28.
- Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1- positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016; 387:1540–50.
- CastelloR, Caputo M. Thyroid disease and gender. Ital J Gender-Specific Med 2019; 5:136-41.
- Parkes GC, Whelan K, Lindsay JO. Smoking in inflammatory bowel disease: impact on disease course and insights into the aetiology of its effect. J Crohns Colitis. 2014; 8:717-25.
- Jantunen R, Juvonen E, Ikkala E, et al. The predictive value of vascular risk factors and gender for the development of thrombotic complications in essential thrombocythemia. Ann Hematol 2001; 80:74–8.
- Karantanis D, Bogsrud TV, Wiseman GA, et al. Clinical significance of diffusely increased 18F-FDG uptake in the thyroid gland. J Nucl Med. 2007; 48:896–901.
|