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Predictors of thyroid adverse events during cancer immunotherapy: a real-life experience at a single center

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Abstract

Background

Thyroid dysfunction is among the most common immune-related adverse events (irAEs) of immune checkpoint inhibitors (ICIs) therapy. Data regarding potential predictors of the development of thyroid irAEs are still limited and sometimes conflicting.

Patients and methods

We assessed potential risk factors and clinical outcomes associated with the onset of thyroid irAEs in a cohort of patients with different types of cancer treated with ICIs at a single center. Clinical and biochemical data, including thyroid function tests and autoantibodies at baseline and during treatment, were collected, and the onset of thyroid irAEs was recorded. Patients with thyroid dysfunction and/or under levothyroxine therapy before starting ICI were excluded.

Results

110 patients (80 M, 30 F, aged 32–85 years; 56.4% non-small-cell lung cancer, 87% treated with anti-PD-1) with complete information were included in the study. Among them, 32 (29%) developed thyroid irAEs during ICIs therapy. Primary hypothyroidism was the most common irAEs, occurring in 31 patients (28.18% of the whole cohort), including 14 patients who experienced a transient thyrotoxicosis. About 60% of irAEs occurred within the first 8 weeks of therapy. At multivariate analysis, anti-thyroid autoantibodies positivity at baseline (OR 18.471, p = 0.022), a pre-existing (autoimmune and non-autoimmune) thyroid disorder (OR 16.307, p < 0.001), and a family history of thyroid diseases (OR = 9.287, p = 0.002) were independent predictors of the development of thyroid irAEs.

Conclusion

Our data confirm the high frequency of thyroid dysfunctions (mostly hypothyroidism) during ICIs, and provide data on valuable predictors of thyroid toxicities that may help clinicians in identifying patients at risk for developing irAEs.

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Funding

This research did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector.

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Author notes

  1. R. M. Ruggeri, C. C. Spagnolo and M. Santarpia have contributed equally to the paper.

  2. R. M. Ruggeri and M. Santarpia share the first author position.

Authors and Affiliations

  1. Endocrinology Unit, Department of Human Pathology of Adulthood and Childhood DETEV “G. Barresi”, University of Messina, Messina, Italy

    R. M. Ruggeri, C. C. Spagnolo, A. Alibrandi, N. Silvestris, S. Cannavò & M. Santarpia

  2. Medical Oncology Unit, Department of Human Pathology of Adulthood and Childhood DETEV “G. Barresi”, University of Messina, Messina, Italy

    R. M. Ruggeri, C. C. Spagnolo, A. Alibrandi, N. Silvestris, S. Cannavò & M. Santarpia

  3. Unit of Statistical and Mathematical Sciences, Department of Economics, University of Messina, Messina, Italy

    R. M. Ruggeri, C. C. Spagnolo, A. Alibrandi, N. Silvestris, S. Cannavò & M. Santarpia

  4. Endocrine Unit, Department of Clinical and Experimental Medicine, “Gaetano Martino” University Hospital, 98125, Messina, Italy

    R. M. Ruggeri

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Patients were treated and followed according to international guidelines and local practices. Local Ethics Research Committee approval was obtained. All procedures performed in this study were in accordance with the ethical standards of the institutional research committee. This study complies with the Declaration of Helsinki.

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All procedures were approved by he Local Ethics Research Committee of the University Hospital Policlinico “G. Martino”. The study was carried out in accordance with the World Medical Association’s Declaration of Helsinki. No animals were used for this study.

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Ruggeri, R.M., Spagnolo, C.C., Alibrandi, A. et al. Predictors of thyroid adverse events during cancer immunotherapy: a real-life experience at a single center. J Endocrinol Invest 46, 2399–2409 (2023). https://doi.org/10.1007/s40618-023-02096-2

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