Hypophysitis Induced by Immune Checkpoint Inhibitors in a Scottish Melanoma Population

Wei, Khor Zhong; Baxter, Mark; Casasola, Richard

doi:10.2217/mmt-2018-0009

Cited by 14 publications

(11 citation statements)

References 38 publications

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“…Twenty studies fulfilled the eligibility criteria and thence were included in the meta-analysis ( Figure 1 ). These studies were published in 25 research articles [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ]. In these studies, 2,909 patients with advanced/metastatic melanoma were treated with pembrolizumab either alone ( n = 2,139) or in combination with other therapies ( n = 770).…”

Section: Resultsmentioning

confidence: 99%

Efficacy of pembrolizumab for advanced/metastatic melanoma: a meta-analysis

et al. 2020

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AbstractThis study evaluates the efficacy of pembrolizumab for the treatment of advanced/metastatic melanoma. The literature search was conducted in electronic databases for studies that evaluated the efficacy and safety of pembrolizumab either alone or in combination with other treatments advanced/metastatic melanoma patients. Random-effects meta-analyses were performed to achieve pooled effect sizes of response and survival rates. The overall objective response rate (ORR) was 34.2% [95% confidence interval (CI): 30.4, 38.0]. However, ORR differed with respect to the history of prior systemic therapy. ORR was lower in studies with over 50% patients with prior therapy (25.5% [22.4, 28.5]) than in studies with under 50% patients with prior therapy (40.1% [34.1, 46.1]). ORR was higher in pembrolizumab monotherapy (32.9% [28.1, 37.7]) than in pembrolizumab–ipilimumab combination (27.6% [24.0, 31.2]). Overall ORR was inversely associated with visceral metastasis and prior systemic therapy. With pembrolizumab treatment, either alone or in combination, the progression-free survival (PFS) was 5.73 months; 12-, 24-, and 60-month PFS rate were 44%, 27%, and 25%, respectively; and 12-, 24-, and 60-month overall survival rates were 65%, 50%, and 41%, respectively. The percentage of AEs that led to treatment discontinuation was 13%. Pembrolizumab monotherapy is a valuable option for the treatment of advanced/metastatic melanoma patients.

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Section: Resultsmentioning

confidence: 99%

Efficacy of pembrolizumab for advanced/metastatic melanoma: a meta-analysis

et al. 2020

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“…Hypophysitis is the inflammation of the pituitary gland, which often leads to irreversible hypopituitarism and can potentially lead to an adrenal crisis if left untreated [ 8 , 12 , 20 ]. Previous data suggest that the incidence of hypophysitis is much higher in patients receiving treatment with anti-CTLA agents as compared to patients treated with other groups of ICIs [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

Endocrine Toxicity and Outcomes in Patients With Metastatic Malignancies Treated With Immune Checkpoint Inhibitors

Ashi

Thapa

Flores

et al. 2021

Journal of the Endocrine Society

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Context Immune checkpoint inhibitors (ICIs) have gained a revolutionary role in management of many advanced malignancies. However, immune-related endocrine events (irEEs), have been associated with their use. irEEs have non-specific clinical presentations and variable timelines, making their early diagnosis challenging. Objective To identify risk factors, timelines, and prognosis associated with irEEs development. Design and setting Retrospective observational study within the Cleveland Clinic center. Patients Metastatic cancer adult patients who received ICIs were included. Methods 570 charts were reviewed to obtain information on demographics, ICIs used, endocrine toxicities, cancer response to treatment with ICI, and overall survival. Main Outcome Measures Incidence of irEEs, time to irEEs development, and overall survival of patients who develop irEEs. Results The final cohort included 551 patients. The median time for the diagnosis of irEEs was 11 weeks. Melanoma was associated with the highest risk for irEEs (31.3%). Ipilimumab appeared to have the highest percentage of irEEs (29.4%), including the highest risk of pituitary insufficiency (11.7%), the most severe (Grade 4 in 60%) and irreversible (100%) forms of irEEs. 45 % of patients with irEEs had adequate cancer response to ICI compared to 28.3 % of patients without irEEs (p= 0.002). Patients with irEEs had significantly better survival compared to patients without irEEs (P <0.001). Conclusions In the adult population with metastatic cancer receiving treatment with ICI, irEEs development may predict tumor response to immunotherapy and a favorable prognosis. Ipilimumab use, combination ICI therapy, and melanoma are associated with a higher incidence of irEEs.

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“…Pembrolizumab has one of the lowest rates of hypophysitis, with <1% of patients reporting this side effect. 6,14 Presenting symptoms include fatigue, weakness, light-headedness, nausea, anorexia, weight loss, headaches, confusion, hyponatremia, and rarely visual disturbances and visual field impairment. 14 Diagnosis of ICI-induced hypophysitis requires diagnostic laboratory analysis including electrolytes and endocrine parameters such as thyroid-stimulating hormone, free T4, cortisol (baseline and The MRI features suggestive of hypophysitis include an enlarged triangular-or dumbbell-shaped pituitary gland with a thickened and not obviously deviated infundibulum, further supported by the absence of the posterior pituitary bright spot on T1-and T2-weighted images.…”

Section: Discussionmentioning

confidence: 99%

Pembrolizumab‐induced hypophysitis with acute progression of Rathke’s cyst

Gamblin

Twitchell

Kundu

et al. 2021

Clinical & Exp Neuroim

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Hypophysitis refers to sellar or suprasellar inflammation that leads to structural changes in the hypothalamic-pituitary axis and varying degrees of pituitary hormonal deficiencies. 1 Hypophysitis is a rare disorder that was first confirmed via magnetic resonance imaging (MRI) in the late 1980s, and the detected incidence has increased dramatically with improvements in imaging quality and understanding of the disease process. Over the past decade, the epidemiological landscape has changed as several newly described forms of hypophysitis have been described, 2 including one caused by immune checkpoint inhibitors (ICIs). Pembrolizumab, an ICI, is a U.S. Food and Drug Administration-approved monoclonal immunoglobulin G4 antibody that induces T-cell-mediated immune responses to various tumors. 3 Pembrolizumab has been established as a rare cause of ICIinduced hypophysitis. [4][5][6] Rathke's cleft cysts (RCCs) are benign lesions first described by Luska in 1860 as "an epithelial area in the capsule of human hypophysis resembling oral mucosa." 7 These benign cysts typically arise within the sella between the lobes of the pituitary. RCCs have been found in 4% to 33% of the population on autopsy. 8,9 Although most are asymptomatic, they can cause mass effect, leading to headaches, pituitary dysfunction, or visual disturbance. 10 Treatment for large or symptomatic cysts almost invariably involves surgical resection to evacuate the cyst and epithelium, typically via a transsphenoidal approach. 11 Small, asymptomatic lesions can be followed radiographically. 12 Despite the relative frequency of RCCs in the population, co-occurrence with ICI-induced hypophysitis has yet to be described.

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Hypophysitis Induced by Immune Checkpoint Inhibitors in a Scottish Melanoma Population

Cited by 14 publications

References 38 publications

Efficacy of pembrolizumab for advanced/metastatic melanoma: a meta-analysis

Efficacy of pembrolizumab for advanced/metastatic melanoma: a meta-analysis

Endocrine Toxicity and Outcomes in Patients With Metastatic Malignancies Treated With Immune Checkpoint Inhibitors

Pembrolizumab‐induced hypophysitis with acute progression of Rathke’s cyst

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