Multinational Association of Supportive Care in Cancer (MASCC) 2020 clinical practice recommendations for the management of immune checkpoint inhibitor endocrinopathies and the role of advanced practice providers in the management of immune-mediated toxicities

Cooksley, Tim; Girotra, Monica; Ginex, Pamela; Gordon, Ruth Ann; Anderson, Ronald; Blidner, Ada G.; Choi, Jennifer N.; Dougan, Michael; Glezerman, Ilya G.; Gupta, Dhiraj; Johnson, Douglas B.; Shannon, Vickie R.; Suarez‐Almazor, María E.; Rapoport, Bernardo Leon

doi:10.1007/s00520-020-05709-1

Cited by 17 publications

(8 citation statements)

References 31 publications

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“…The increasing trend of incidence of ICI-TDs may be explained by a more profound and prevalent understanding of the disease by both oncologists and endocrinologists. In a recent couple of years, patients on ICIs therapy were arranged for regular surveillance of thyroid function by the oncologists along with the latest published guidelines for ICI therapy, 7 which may contribute to the increasing diagnosis rate of ICI-TDs by reporting years. Due to the decreasing prescription of anti-CTLA-4 (ipilimumab) mono-therapy and more frequent application of anti-PD-1 + anti-CTLA-4 therapy, the incidence of anti-CTLA-4 mono-therapy induced thyroid dysfunction reduced over time.…”

Section: Discussionmentioning

confidence: 99%

Immune Checkpoint Inhibitor-related New-onset Thyroid Dysfunction: A Retrospective Analysis Using the US FDA Adverse Event Reporting System

Yao

Yuan

et al. 2022

The Oncologist

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Objectives The study aimed to investigate the prevalence and demographic characteristics of an immune checkpoint inhibitor (ICI)-related thyroid dysfunction (ICI-TD), and to explore risk factors of poor clinical outcome using data from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Methods This is a retrospective study. All cases, aged over 18-year olds, of new-onset or new-diagnosed thyroid dysfunction related to FDA-approved ICIs from January 1, 2011 to December 31, 2020 were identified using FAERS. Data of age, gender, other combined endocrinopathies related to ICIs besides ICI-TDs, and the prognosis was analyzed. Results In total, 2.60% (2971/114 121) cases of ICI-TDs were identified. Among them, 1842 (62.0%) developed hypothyroidism, 675 (22.7%) were hyperthyroidism, and 454 (15.3%) presented in thyroiditis without the mention of thyroid function. Patients on anti- programmed cell death protein-1 (PD-1) therapy displayed higher risk of hypothyroidism compared with other 3 regimens, respectively (P < .01 for all). The likelihood of other immune-related endocrinopathies in patients on the combination therapy of anti-cytotoxic T-cell-associated protein-4 (CTLA-4) and anti-PD-1 was significantly elevated than anti-PD-1 (odds ratio [OR] 2.362, 95% confidence interval [CI] [1.925-2.898], P < .001) and anti-programmed death-ligand 1 (PD-L1) regimens (OR 4.857, 95%CI [3.228-7.308], P < .001). The risk of severe cases was positively related to hypothyroidism in individuals on anti-PD-1 therapy (OR 1.587, 95%CI [1.146-2.197], P = .005) and those on anti-CTLA-4 therapy (OR 3.616, 95%CI [1.285-10.171], P = .015). The risk of severe cases was positively associated with the comorbidity with other endocrinopathies (anti-PD-1 group, OR 0.285, 95%CI [0.200-0.467], P < .001; anti-PD-1+anti-CTLA-4 group, OR 0.574, 95%CI [0.371-0.890], P = .013). Conclusions Regular monitor of thyroid function is indispensable, since ICI-TDs manifested as hypothyroidism or hyperthyroidism, especially those on the combination therapy. Awareness among health care professionals is critical when hypothyroidism occurs, which might indicate poor clinical outcomes.

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Section: Discussionmentioning

confidence: 99%

Immune Checkpoint Inhibitor-related New-onset Thyroid Dysfunction: A Retrospective Analysis Using the US FDA Adverse Event Reporting System

Yao

Yuan

et al. 2022

The Oncologist

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“…Generally, pharmacological dose of glucocorticoids is used as first-line therapy for treatment of irAEs. However, in terms of ICI-related hypophysitis, it is recommended to use physiological doses of glucocorticoids as a replacement therapy unless the presence of severe visual disturbance or intolerable headache because pharmacological dose of glucocorticoids does not restore pituitary function and recent study suggested high-dose glucocorticoids in patients with ICI-related hypophysitis might impair the effect of ICIs and survival [ 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

Mechanistic insights into immune checkpoint inhibitor-related hypophysitis: a form of paraneoplastic syndrome

Kanie

Iguchi

Bando

et al. 2021

Cancer Immunol Immunother

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Background Immune checkpoint inhibitors (ICIs) as a cancer immunotherapy have emerged as a treatment for multiple advanced cancer types. Because of enhanced immune responses, immune-related adverse events (irAEs), including endocrinopathies such as hypophysitis, have been associated with the use of ICIs. Most underlying mechanisms of ICI-related hypophysitis remain unclear, especially for programmed cell death-1 (PD-1)/PD-1 ligand 1 (PD-L1) inhibitors. We hypothesized that ICI-related hypophysitis is associated with paraneoplastic syndrome caused by ectopic expression of pituitary-specific antigens. Methods Twenty consecutive patients with ICI-related hypophysitis between 2017 and 2019 at Kobe University Hospital were retrospectively analyzed. Circulating anti-pituitary antibodies were detected using immunofluorescence staining and immunoblotting. Ectopic expression of pituitary autoantigens in tumor specimens was also examined. Results Eighteen patients were treated with PD-1/PD-L1 inhibitors, and two were treated with a combination of cytotoxic T-lymphocyte antigen-4 (CTLA-4) and PD-1 inhibitors. All patients showed adrenocorticotropic hormone (ACTH) deficiency and additionally, three showed thyroid-stimulating hormone (TSH) deficiency, and one showed gonadotropin-releasing hormone (GnRH) deficiency. Among these patients, three exhibited anti-pituitary antibodies, two with anti-corticotroph antibody and one with anti-somatotroph antibody. Interestingly, the anti-corticotroph antibody recognized proopiomelanocortin (POMC) and those two patients exhibited ectopic ACTH expression in the tumor, while the patients without anti-corticotroph antibody did not. Conclusions We demonstrated 10% of PD-1/PD-L1 inhibitors-related hypophysitis were associated with the autoimmunity against corticotrophs and maybe caused as a form of paraneoplastic syndrome, in which ectopic expression of ACTH in the tumor was observed. It is also suggested that the pathophysiology is heterogenous in ICI-related hypophysitis.

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“…Long-term hormone replacement therapy is therefore necessary. 1,5 Lichen and autoimmune thyroid disorders are more frequent in females, and some data suggest they share genetic risk. Thus, their co-occurrence in some patients could be explained by a common pathogenic mechanism.…”

Section: E396 |mentioning

confidence: 99%

Cutaneous, oral and genital lichenoid reactions associated with retifanlimab, a new PD‐1 inhibitor

Damme

Demols

Marmol

2022

Acad Dermatol Venereol

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Multinational Association of Supportive Care in Cancer (MASCC) 2020 clinical practice recommendations for the management of immune checkpoint inhibitor endocrinopathies and the role of advanced practice providers in the management of immune-mediated toxicities

Cited by 17 publications

References 31 publications

Immune Checkpoint Inhibitor-related New-onset Thyroid Dysfunction: A Retrospective Analysis Using the US FDA Adverse Event Reporting System

Immune Checkpoint Inhibitor-related New-onset Thyroid Dysfunction: A Retrospective Analysis Using the US FDA Adverse Event Reporting System

Mechanistic insights into immune checkpoint inhibitor-related hypophysitis: a form of paraneoplastic syndrome

Cutaneous, oral and genital lichenoid reactions associated with retifanlimab, a new PD‐1 inhibitor

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