Pembrolizumab-Induced Adrenal Insufficiency in Patients with Untreated Advanced Non-Small Cell Lung Cancer: A Case Series

Sonehara, Kei; Tateishi, Kazunari; Araki, Taisuke; Komatsu, Masamichi; Akahane, Jumpei; Yamamoto, Hiroshi; Hanaoka, Masayuki

doi:10.1159/000519597

Cited by 7 publications

(5 citation statements)

References 13 publications

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“…Upon literature review, there are very few cases documenting a diagnosis of AI following treatment withdrawal. In a case series by Sonehara et al, five out of 49 patients developed AI, and all five of the patients presented with symptoms while receiving treatment with pembrolizumab [ 7 ]. In a retrospective study by Kurokawa et al, nine out of 10 patients were diagnosed with AI while being treated with pembrolizumab and only one patient developed AI after pembrolizumab was discontinued; in their case, it was 4.5 months later [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

Pembrolizumab-Induced Adrenal Insufficiency Presenting Eight Months After Cessation of Treatment

Zilberman¹,

Rafii²,

Giunta³

2023

Cureus

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Pembrolizumab is a monoclonal antibody that functions as an immune checkpoint inhibitor. It is an FDAapproved immunotherapy used to treat various malignancies. With its wide use in cancer therapy, there are many known side effects. It is a common cause of endocrinopathies such as thyroid disease and adrenal insufficiency (AI). AI has been most commonly reported during active treatment cycles with pembrolizumab, as well as quickly after the termination of treatment. However, we describe a case of pembrolizumabinduced AI with an onset at eight months following the discontinuation of treatment and discuss prompt treatment when AI is diagnosed.

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Section: Discussionmentioning

confidence: 99%

Pembrolizumab-Induced Adrenal Insufficiency Presenting Eight Months After Cessation of Treatment

Zilberman¹,

Rafii²,

Giunta³

2023

Cureus

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“…We were left with 23 publications to evaluate in full text after removing duplicates and analyzing titles and abstracts. A total of eleven studies with 1,417 patients were included in the final analysis (26,(30)(31)(32)(33)(34)(35)(36)(37)(38)(39). Figure 1 uses a PRISMA flowchart to show the research selection process.…”

Section: Characteristics Of Studiesmentioning

confidence: 99%

“…In the field of cancer treatment, GNRI has been related to survival following chemotherapy, surgery, or chemoradiotherapy in various malignancies (21)(22)(23). Additionally, although GNRI was initially created for older people, it can be used for younger populations as well (24)(25)(26).…”

Section: Introductionmentioning

confidence: 99%

Low geriatric nutritional risk index as a poor prognostic biomarker for immune checkpoint inhibitor treatment in solid cancer

Zhang,

Wang,

Kuang

et al. 2023

Front. Nutr.

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ObjectiveIn this investigation, we focused on the geriatric nutritional risk index (GNRI), a comprehensive metric that takes into account the patient’s ideal weight, actual weight, and serum albumin levels to measure malnutrition. Our primary objective was to examine the predictive value of GNRI-defined malnutrition in determining the response to immunotherapy among cancer patients.MethodsRelevant articles for this study were systematically searched in PubMed, the Cochrane Library, EMBASE, and Google Scholar up to July 2023. Our analysis evaluated overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) as clinical outcomes.ResultsThis analysis comprised a total of eleven articles encompassing 1,417 patients. The pooled results revealed that cancer patients with low GNRI levels exhibited shorter OS (HR: 2.64, 95% CI: 2.08–3.36, p < 0.001) and PFS (HR: 1.87, 95% CI: 1.46–2.41, p < 0.001), and lower ORR (OR: 0.46, 95% CI: 0.33–0.65, p < 0.001) and DCR (OR: 0.42, 95% CI: 0.29–0.61, p < 0.001). Sensitivity analyses confirmed that the above results were stable. Egger’s and Begg’s tests revealed that there was no publication bias in the above results.ConclusionOur results imply that the GNRI is a useful predictor of immunotherapy response in cancer patients.

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“… 3 One such endocrinopathy is adrenal insufficiency (AI), which has a reported incidence of 0.98%. 2 We describe a case of secondary AI and primary hypothyroidism in a 59-year-old man secondary to pembrolizumab use for lung cancer.…”

Section: Introductionmentioning

confidence: 98%

“…1 Pembrolizumab, a humanized IgG4 monoclonal antibody, inhibits the PD-1 receptor and is approved for various malignancies, including melanoma, non-small cell lung cancer (NSCLC), Hodgkin lymphoma, cervical cancer, and renal cell carcinoma. 2,3 Pembrolizumab's mechanism involves selectively silencing immunological cell surface proteins, thereby shielding both healthy and tumor cells from immune system-induced apoptosis. 4 Although ICIs have improved the survival rates in those suffering from malignancy, rare immune-related adverse effects such as endocrinopathies can occur.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous Presentation of Secondary Adrenal Insufficiency and Primary Hypothyroidism due to Pembrolizumab: A Case Report

Khatri,

Alom,

Kashfi

et al. 2023

Journal of Investigative Medicine High Impact Case Reports

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Checkpoint inhibitors have gained increased traction in recent years as they have improved prognosis in various malignancies. Pembrolizumab, an anti-programmed cell death protein (PD-1) monoclonal antibody, has become a first-line chemotherapeutic agent for stage II non–small cell lung cancer since 2019. Although much more common with nivolumab, several immune-related adverse effects, particularly endocrinopathies, have been linked with pembrolizumab. We describe a case of a 59-year-old man with a history of unspecified lung cancer who presented with severe hyponatremia later attributed to secondary adrenal insufficiency and accompanying primary hypothyroidism secondary to pembrolizumab. Diagnosing adrenal insufficiency in patients on immune checkpoint inhibitors like pembrolizumab can be challenging due to nonspecific symptoms, making it crucial to rule out other causes of hyponatremia. Immunotherapy is known to cause thyroid immune-related adverse events, and anti-thyroid antibodies may not always be present in the diagnosis of hypothyroidism. Although there are some reported cases of pembrolizumab-induced adrenal insufficiency, the link between immunotherapy and endocrine disorders remains unclear. To our knowledge, no case reports exist that describe both primary hypothyroidism and secondary adrenal insufficiency after taking pembrolizumab, although such cases have been documented with axitinib. Timely diagnosis and treatment of adrenal insufficiency is crucial to prevent adverse effects, especially in patients with cancer receiving immunotherapy, as highlighted in this case.

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Pembrolizumab-Induced Adrenal Insufficiency in Patients with Untreated Advanced Non-Small Cell Lung Cancer: A Case Series

Cited by 7 publications

References 13 publications

Pembrolizumab-Induced Adrenal Insufficiency Presenting Eight Months After Cessation of Treatment

Pembrolizumab-Induced Adrenal Insufficiency Presenting Eight Months After Cessation of Treatment

Low geriatric nutritional risk index as a poor prognostic biomarker for immune checkpoint inhibitor treatment in solid cancer

Simultaneous Presentation of Secondary Adrenal Insufficiency and Primary Hypothyroidism due to Pembrolizumab: A Case Report

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