Abstract #514 Secondary Adrenal Insufficiency Due to the Immune Checkpoint Inhibitor Pembrolizumab

Data on the diagnosis, natural course and management of immune checkpoint inhibitor (ICI) related hypophysitis (irH) are limited. We propose this study to validate the diagnostic criteria, describe characteristics and hormonal recovery and investigate factors associated with occurrence and recovery of irH. A retrospective study including patients with suspected irH at the University of Texas MD Anderson Cancer Center from 5/2003 to 8/2017 was conducted. IrH was defined as: (1) ACTH or TSH deficiency plus MRI changes or (2) ACTH and TSH deficiencies plus headache/fatigue in the absence of MRI findings. We found that of 83 patients followed for a median of 1.75 years (range 0.6-3), the proposed criteria used at initial evaluation accurately identified 61/62 (98%) irH cases. In the irH group (n=62), the most common presentation were headache (60%), fatigue (66%), central hypothyroidism (94%), central adrenal insufficiency (69%) and MRI changes (77%). Compared with non-Ipilimumab (Ipi) regimens, Ipi has a stronger association with irH occurrence (p=0.004) and a shorter time to irH development (p<0.01). Thyroid, gonadal and adrenal axis recovery occurred in 24%, 58% and 0% patients, respectively. High dose steroids (HDS) or ICI discontinuation were not associated with hormonal recovery. In the non-irH group (n=19), one patient had isolated central hypothyroidism and 6 had isolated central adrenal insufficiency. All remained on hormone therapy at last follow up. We propose a strict definition of irH that identifies the vast majority of patients. HDS and ICI discontinuation is not always beneficial. Long term follow up to assess recovery is needed.

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Immune Checkpoint Inhibitor-Associated New-Onset Primary Adrenal Insufficiency: A Retrospective Analysis Using The FAERS

10.21203/rs.3.rs-702598/v1 ◽

2021 ◽

Author(s):

Difei Lu ◽

Jun Yao ◽

Geheng Yuan ◽

Ying Gao ◽

Junqing Zhang ◽

...

Keyword(s):

Body Weight ◽

Adrenal Insufficiency ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor ◽

Adverse Event Reporting System ◽

Occurrence Rate ◽

Primary Adrenal Insufficiency ◽

Risk Of Death ◽

New Onset

Abstract Background Our study aimed to investigate the prevalence and demographic characteristics of immune checkpoint inhibitor-associated primary adrenal insufficiency (ICI-PAI), and to explore the risk factors of clinical outcome using data from the US FDA Adverse Event Reporting System (FAERS). Methods This is a retrospective study. All cases of new-onset or newly-diagnosed primary adrenal insufficiency associated with FDA approved ICIs from 1st January 2007 to 31st December 2020 were identified and collected using FAERS. Data of age, sex category, body weight of participated individuals, the reporting year and the prognosis of cases, and other accompanied endocrinopathies related to ICIs were analyzed. Results The incidence of ICI-PAI was 1.03% (1180/114121). The application of the combination therapy of anti-CTLA-4 and anti-PD-1 was related to higher risk of PAI compared with anti-PD-1 group (χ2 = 92.88, p < 0.001). Male and elder individuals showed higher risk of ICI-PAI (male vs. female, 1.17% vs. 0.94%, χ2 = 12.55, p < 0.001; age < 65 vs. ≥65, 1.20% vs. 1.41%, χ2 = 6.89, p = 0.009). The co-occurrence rate of other endocrinopathies aside from PAI was 24.3%, which showed a higher trend in patients on nivolumab-ipilimumab treatment compared with those on PD-1 inhibitors (χ2 = 3.227, p = 0.072). Body weight was negatively associated with the risk of death in the study population [p = 0.033 for the regression model; B=-0.017, OR 0.984, 95%CI (0.969–0.998), p = 0.029]. Conclusions ICI-associated PAI is a rare but important irAE. Male and elder patients have higher risk of ICI-PAI. Awareness among clinicians is critical when patients with lower body weight develop PAI, which indicates poor clinical outcomes.

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