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Article

Immune-Related Endocrine Dysfunctions in Combined Modalities of Treatment: Real-World Data

1
Department of Clinical Oncology, The University of Hong Kong, Hong Kong, China
2
Department of Clinical Oncology, Queen Mary Hospital, Hong Kong, China
*
Author to whom correspondence should be addressed.
Academic Editors: Mohd W. Nasser, Klaus Podar, Constantin N. Baxevanis, Shahab Uddin and Martin Sattler
Cancers 2021, 13(15), 3797; https://doi.org/10.3390/cancers13153797
Received: 29 May 2021 / Revised: 16 July 2021 / Accepted: 25 July 2021 / Published: 28 July 2021
(This article belongs to the Special Issue Targeting Signal Transduction Pathways in Cancer)
Immune-checkpoint inhibitors (ICI) have been increasingly used in the management of various types of cancers. More studies and guidelines also recommended the combination of ICI with other anti-cancer agents to improve the efficacy and treatment outcome. This retrospective study showed that the combination of ICI and targeted agents increased the risk of immune-related endocrine dysfunction and hypothyroidism. Moreover, older patients on ICI had a higher risk of immune-related diabetes mellitus. ICI is safe and well-tolerated regardless of age, but close monitoring of fasting glucose is essential in older populations.
The number of immune-related endocrine dysfunctions (irEDs) has concurrently increased with the widespread use of immunotherapy in clinical practice and further expansion of the approved indications for immune checkpoint inhibitor (ICI) in cancer management. A retrospective analysis was conducted on consecutive patients ≥18 years of age with advanced solid malignancies who had received at least one dose of anti-programmed cell death protein 1 (anti-PD-1) and/or anti-CTLA4 antibodies between January 2014 and December 2019 at a university hospital in Hong Kong. Patients were reviewed up to two months after the last administration of an ICI. The types, onset times and grades of irEDs, including hypothyroidism, hyperthyroidism, adrenal insufficiency and immune-related diabetes mellitus, were recorded. Factors associated with irEDs were identified using multivariate analysis. A total of 953 patients (male: 603, 64.0%; median age: 62.0 years) were included. Of these, 580 patients (60.9%) used ICI-alone, 132 (13.9%) used dual-ICI, 187 (19.6%) used an ICI combined with chemotherapy (chemo + ICI), and 54 (5.70%) used immunotherapy with a targeted agent (targeted + ICI). A significantly higher proportion of patients using targeted + ICI had irEDs and hypothyroidism; in contrast, a higher proportion of patients using dual-ICI had adrenal insufficiency. There was no significant difference in the incidence of irED between the younger (<65 years) and older (≥65 years) patients. Using logistic regression, only treatment type was significantly associated with irEDs. Notably, older patients had a higher risk of having immune-related diabetes mellitus. This large, real-world cohort demonstrates that targeted + ICI has a higher risk of overall irED and hypothyroidism. Immunotherapy is safe and well-tolerated regardless of age, but close monitoring of fasting glucose is essential in older populations. View Full-Text
Keywords: immune checkpoint inhibitors; immune-related endocrine dysfunction; hypothyroidism; targeted therapy; malignancy immune checkpoint inhibitors; immune-related endocrine dysfunction; hypothyroidism; targeted therapy; malignancy
MDPI and ACS Style

Chan, W.-L.; Choi, H.C.-W.; Ho, P.P.-Y.; Lau, J.K.-S.; Tse, R.P.-Y.; Au, J.; Lam, V.; Liu, R.; Ho, I.; Wong, C.; Cheung, B.; Lam, E.; Chow, D.; Lam, K.-O.; Yuen, K.-K.; Kwong, D.L.-W. Immune-Related Endocrine Dysfunctions in Combined Modalities of Treatment: Real-World Data. Cancers 2021, 13, 3797. https://doi.org/10.3390/cancers13153797

AMA Style

Chan W-L, Choi HC-W, Ho PP-Y, Lau JK-S, Tse RP-Y, Au J, Lam V, Liu R, Ho I, Wong C, Cheung B, Lam E, Chow D, Lam K-O, Yuen K-K, Kwong DL-W. Immune-Related Endocrine Dysfunctions in Combined Modalities of Treatment: Real-World Data. Cancers. 2021; 13(15):3797. https://doi.org/10.3390/cancers13153797

Chicago/Turabian Style

Chan, Wing-Lok, Horace C.-W. Choi, Patty P.-Y. Ho, Johnny K.-S. Lau, Rosa P.-Y. Tse, Joyce Au, Vivian Lam, Ronald Liu, Isaac Ho, Charlotte Wong, Ben Cheung, Eric Lam, Daryn Chow, Ka-On Lam, Kwok-Keung Yuen, and Dora L.-W. Kwong 2021. "Immune-Related Endocrine Dysfunctions in Combined Modalities of Treatment: Real-World Data" Cancers 13, no. 15: 3797. https://doi.org/10.3390/cancers13153797

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