Thyroid dysfunction after immune checkpoint inhibitors in a single-centre UK pan-cancer cohort: A retrospective study.

Autor: Kennedy OJ; The Christie NHS Foundation Trust, Manchester, M20 4BX, UK; Division of Cancer Sciences, The University of Manchester, Manchester, M13 9PL, UK. Electronic address: ojk@doctors.org.uk., Ali N; The Christie NHS Foundation Trust, Manchester, M20 4BX, UK., Lee R; The Christie NHS Foundation Trust, Manchester, M20 4BX, UK; Division of Cancer Sciences, The University of Manchester, Manchester, M13 9PL, UK., Monaghan P; Division of Cancer Sciences, The University of Manchester, Manchester, M13 9PL, UK; The Christie Pathology Partnership, Manchester, M20 4BX, UK., Adam S; The Christie NHS Foundation Trust, Manchester, M20 4BX, UK; Division of Cancer Sciences, The University of Manchester, Manchester, M13 9PL, UK., Cooksley T; The Christie NHS Foundation Trust, Manchester, M20 4BX, UK., Lorigan P; The Christie NHS Foundation Trust, Manchester, M20 4BX, UK; Division of Cancer Sciences, The University of Manchester, Manchester, M13 9PL, UK.
Jazyk: angličtina
Zdroj: European journal of cancer (Oxford, England : 1990) [Eur J Cancer] 2024 May; Vol. 202, pp. 113949. Date of Electronic Publication: 2024 Feb 21.
DOI: 10.1016/j.ejca.2024.113949
Abstrakt: Purpose: This study investigated thyroid dysfunction with immune checkpoint inhibitors (ICIs) in terms of proportions affected, risk factors, thyroid sequelae, and overall survival (OS).
Methods: Among patients with normal baseline free T4 (fT4) and thyroid stimulating hormone (TSH) receiving ICIs at a large cancer centre, proportions of hyperthyroidism/hypothyroidism were determined (any, subclinical [normal fT4, abnormal TSH], overt [abnormal fT4, abnormal TSH], isolated hyperthyroxinaemia/hypothyroxinaemia and secondary) with onset times and subsequent thyroid statuses. Associations of overt dysfunction with OS were estimated using Cox regression and methods robust to immortal time bias (time-dependent Cox regression and 3- and 6-month landmark analyses). Associations of baseline variables with overt hyperthyroidism and hypothyroidism were estimated using Fine and Gray regression.
Results: Of 1349 patients, 34.2% developed hyperthyroidism (10.3% overt), including 54.9% receiving combination ICIs, while 28.2% developed hypothyroidism (overt 9.3%, secondary 0.5%). A third of overt hypothyroidism cases occurred without preceding hyperthyroidism. Subclinical thyroid dysfunction returned directly to normal in up to half. Overt hyperthyroidism progressed to overt hypothyroidism in 55.4% (median 1.6 months). Melanoma treatment in the adjuvant vs. advanced setting caused more overt hyperthyroidism (12.1% vs. 7.5%) and overt hypothyroidism (14.5% vs. 9.7%). Baseline eGFR < 60 mL/min/1.73 m 2 (HR=1.68, 1.07-2.63) was associated with overt hyperthyroidism and sex (HR=0.60, 0.42-0.87) and TSH (4th vs. 1st quartile HR=1.87, 1.10-3.19) with overt hypothyroidism. Overt dysfunction was associated with OS in the Cox analysis (HR=0.65, 0.50-0.85, median follow-up 22.2 months) but not in the time-dependent Cox (HR=0.79, 0.60-1.03) or landmark analyses (3-month HR=0.74, 0.51-1.07; 6-month HR=0.91, 0.66-1.24).
Conclusion: Thyroid dysfunction affects up to half of patients receiving ICIs. The association with OS is unclear after considering immortal time bias. The clinical courses include recovery, thyrotoxicosis and de novo overt hypothyroidism. Adjuvant treatment for melanoma, where longer-term harms are of concern, causes more frequent/aggressive dysfunction.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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