The Impact of High-Dose Glucocorticoids on the Outcome of Immune-Checkpoint Inhibitor–Related Thyroid Disorders

Ma, Chanjuan; Hodi, F. Stephen; Giobbie‐Hurder, Anita; Wang, Xiaocheng; Zhou, Jing; Zhang, Amy; Zhou, Ying; Mao, Fei; Angell, Trevor Te.; Andrews, Chelsea; Hu, Jiani; Barroso‐Sousa, Romualdo; Kaiser, Ursula B.; Tolaney, Sara M.; Min, Le

doi:10.1158/2326-6066.cir-18-0613

Cited by 53 publications

(50 citation statements)

References 43 publications

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“…ICIs can be continued in the context of thyroiditis, and most patients are simply treated with thyroid replacement. Treatment with corticosteroids has not been shown to affect the duration or degree of thyroid dysfunction 68…”

Section: Clinical Presentation Of Checkpoint Inhibitor Associated Autmentioning

confidence: 99%

Autoimmune complications of immunotherapy: pathophysiology and management

Chan

Bass

2020

BMJ

100

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Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that target inhibitory molecules, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), or its ligand, programmed cell death protein ligand 1 (PD-L1), and lead to immune activation in the tumor micro-environment. ICIs can induce durable treatment responses in patients with advanced cancers, but they are commonly associated with immune related adverse events (irAEs) such as rash, colitis, hepatitis, pneumonitis, and endocrine and musculoskeletal disorders. Almost all patients experience some form of irAE, but high grade irAEs occur in approximately half of those on combination therapy (eg, anti-CTLA-4 plus anti-PD-1), and up to one quarter receiving ICI monotherapy. Fatal irAEs occur in approximately 1.2% of patients on CTLA-4 blockade and 0.4% of patients receiving PD-1 or PD-L1 blockade, and case fatality rates are highest for myocarditis and myositis. IrAEs typically occur in the first three months after ICI initiation, but can occur as early as one day after the first dose to years after ICI initiation. The mainstay of treatment is with corticosteroids, but tumor necrosis factor inhibitors are commonly used for refractory irAEs. Although ICIs are generally discontinued when high grade irAEs occur, ICI discontinuation alone is rarely adequate to resolve irAEs. Consensus guidelines have been published to help guide management, but will likely be modified as our understanding of irAEs grows.

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Section: Clinical Presentation Of Checkpoint Inhibitor Associated Autmentioning

confidence: 99%

Autoimmune complications of immunotherapy: pathophysiology and management

Chan

Bass

2020

BMJ

100

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“…These patients may present with elevated Thyroid stimulating hormone (TSH) and low levels of T4. According to a retrospective cohort study by Ma et al [ 24 ], the median time to onset of hypothyroidism in patients receiving pembrolizumab (PD-1 inhibitor) was found to be 84 d (range: 43-544; P = 0.333) . For those receiving nivolumab (PD-1 inhibitor) and ipilimumab (CTLA-4 inhibitor) + nivolumab (PD-1 inhibitor), the median time to onset was 84 d (range: 14–154; P = 0.002) and 62 d (range: 21–141; P = 0.057) respectively[ 24 ].…”

Section: Endocrinementioning

confidence: 99%

“…Furthermore, many patients may commonly be asymptomatic, with the hyperthyroid state uncovered on routine laboratory investigations[ 21 ]. Ma et al [ 24 ] found that the median time to onset of thyrotoxicosis in patients treated with pembrolizumab (PD-1 inhibitor) was 44 d (range: 19-447; P = 0.593), while time for those receiving nivolumab (PD-1 inhibitor) was 56 d (range: 13-126; P = 0.004) and ipilimumab (CTLA-4 inhibitor) + nivolumab (PD-1 inhibitor) was 21 d (range: 7-64; P = 0.158). It is abundantly evident from these studies that the use of combination therapy leads to a more rapid symptom onset.…”

Section: Endocrinementioning

confidence: 99%

Systemic adverse effects and toxicities associated with immunotherapy: A review

Kichloo

Albosta

Dahiya

et al. 2021

WJCO

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Immunotherapy is rapidly evolving secondary to the advent of newer immunotherapeutic agents and increasing approval of the current agents by the United States Food and Drug Administration to treat a wide spectrum of cancers. Immunotherapeutic agents have gained immense popularity due to their tumor-specific action. Immunotherapy is slowly transforming into a separate therapeutic entity, and the fifth pillar of management for cancers alongside surgery, radiotherapy, chemotherapy, and targeted therapy. However, like any therapeutic entity it has its own adverse effects. With the increasing use of immuno-therapeutic agents, it is vital for physicians to acquaint themselves with these adverse effects. The aim of this review is to investigate the common systemic adverse effects and toxicities associated with the use of different classes of immunotherapeutic agents. We provide an overview of potential adverse effects and toxicities associated with different classes of immunotherapeutic agents organized by organ systems, as well as an extensive discussion of the current recommendations for treatment and clinical trial data. As we continue to see increasing usage of these agents in clinical practice, it is vital for physicians to familiarize themselves with these effects.

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“…Typically, hypothyroidism [elevated thyroid-stimulating hormone (TSH), normal or low FT4] presents with nonspecific symptoms such as fatigue, asthenia, cold intolerance, and dry skin. The management of hypothyroidism consists of thyroid hormone replacement (levothyroxine), usually starting with 0.8–1.0 µg kg −1 day −1 (Ma et al, 2019) and supportive care. ICI therapy is withheld in severe cases until symptoms resolve to baseline with appropriate supplementation.…”

Section: Common Iraes and The Relevant Management In Hnsccmentioning

confidence: 99%

“…In the most recent study of MA and colleagues, high-dose glucocorticoids (HDGs) did not improve the outcome of ICI-related thyroid disorders; therefore, routine use of HDGs in patients with suspected thyroid disorders such as thyrotoxicosis is not recommended. In addition, they suggested using HDGs in patients who present with symptoms of thyroid storm or in patients with cardiac disease (Ma et al, 2019).…”

Section: Common Iraes and The Relevant Management In Hnsccmentioning

confidence: 99%

Immune Checkpoint Inhibitor Toxicity in Head and Neck Cancer: From Identification to Management

et al. 2019

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Benefiting from the continuously clarifying underlying biology of immune checkpoints and ligand–receptor interactions, the emergence of new anticancer treatment strategy, immunotherapy has shown substantial benefits on several liquid and solid tumors. Immune checkpoint inhibitors (ICIs) can block the negative regulatory components and enhance the T cell function, thus leading to prominent anticancer activity. On account of their promising effect on various malignancies shown in clinical trials, ICIs have been considered to be the most potent anticancer agents in the near future. Head and neck cancer is the seventh most common neoplasm worldwide, and the gross 5-year survival rate was only 60%. Managing locoregionally advanced, recurrent, or metastatic head and neck tumors is still a challenging problem for both oncologists and surgeons. Recent clinical trials employing the immune-modulating antibodies that target cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death 1 (PD-1) herald a new era of anticancer therapy. However, like all other anticancer drugs, ICIs also have side effects while upregulating the immune system to enhance antitumor response, which were known as immune-related adverse events (irAEs). Generally, most irAEs were transient, but sometimes they can cause serious organ dysfunction, even fatal. In addition, due to the distinct anatomical feature, advanced head and neck tumors often affect the upper aerodigestive tract and cause serious dyspnea or dysphagia. Toxicities of ICIs may be more lethal for such patients. Thus, with the increasing application of anti-checkpoint agents in head and neck cancer, there is urgent need to ascertain the safety of this novel treatment strategy. Here, we compile this review of existing clinical trials on the toxicity of ICIs during cancer treatment. The particular clinical manifestation, characteristics of complication development in fatal cases, and the management strategies were discussed. This may provide vital information for future oncology trials and clinical practice.

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The Impact of High-Dose Glucocorticoids on the Outcome of Immune-Checkpoint Inhibitor–Related Thyroid Disorders

Cited by 53 publications

References 43 publications

Autoimmune complications of immunotherapy: pathophysiology and management

Autoimmune complications of immunotherapy: pathophysiology and management

Systemic adverse effects and toxicities associated with immunotherapy: A review

Immune Checkpoint Inhibitor Toxicity in Head and Neck Cancer: From Identification to Management

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