Eosinophil counts can be a predictive marker of immune checkpoint inhibitor-induced secondary adrenal insufficiency: a retrospective cohort study

Abstract

Immune checkpoint inhibitors (ICIs) treatment can result in endocrine immune-related adverse events (irAEs), including pituitary dysfunction. Quick diagnosis of secondary adrenal insufficiency (AI) is challenging because no universal definition of ICI-induced secondary AI has been agreed. The aim of this study was to clarify the clinical features of ICI-induced secondary AI that can be used for screening in standard clinical practice. This retrospective study was performed using the medical records of patients who received ICIs at Hirosaki University Hospital between 1 September 2014 and 31 January 2021. Longitudinal clinical data of patients who developed AI were analyzed and compared with the data of thyroid irAEs. Regression analysis showed a significant correlation between ICI-induced secondary AI and absolute or relative eosinophil counts at pre-onset of AI, as well as differences or rate of increase in eosinophil counts at baseline and at pre-onset. Absolute eosinophil counts > 198.36/µL or relative eosinophil counts > 5.6% at pre-onset, and a difference of 65.25/µL or a rate of eosinophil count increase of 1.97 between the baseline and at pre-onset showed the best sensitivity and specificity. This is the first report to demonstrate that eosinophil counts can be a predictor of ICI-induced secondary AI.

The Association between a Decrease in On-Treatment Neutrophil-to-Eosinophil Ratio (NER) at Week 6 after Ipilimumab Plus Nivolumab Initiation and Improved Clinical Outcomes in Metastatic Renal Cell Carcinoma

“…Osawa et al found that peripheral eosinophilia (defined as AEC ≥ 330/µL) at week 6 was associated with a 2.8-fold higher risk of irAEs [ 46 ]. Studies have observed such associations in ICI-induced adrenal insufficiency [ 47 ], hypopituitarism [ 48 ], cutaneous irAEs [ 49 ], and pneumonitis [ 50 ]. Given that irAEs have been associated with improved outcomes in ICI-treated cancer patients [ 51 ], the association between eosinophil elevation and irAEs is expected.…”

Nivolumab plus ipilimumab induced endocrinopathy and acute interstitial nephritis in metastatic sarcomatoid renal-cell carcinoma: A case report and review of literature

“…Previous studies have observed that patients frequently developed eosinophilia prior to the onset of ICI induced adrenal insufficiency and that eosinophilia may be an independent predictor for a favorable response to therapy ( 13 , 36 – 40 ). However it should be noted that eosinophilia can also be an early sign of adrenal insufficiency independent of ICI therapy ( 41 ).…”

Laboratory Workup of Hypereosinophilia

“…Solid tumors like carcinomas arising from lung, GIT, hepatobiliary system, thyroid, and genitourinary system 15 Other rare causes: Graft versus host disease, 17 adrenal insufficiency, 18 atheroembolic disease, 19 Gleich syndrome (episodic angioedema with eosinophilia (EAE) 20 Abbreviations: ADA, adenosine deaminase; CVID, common variable immunodeficiency; GIT, gastrointestinal tract; HE/HES, hypereosinophilia/hypereosinophilic syndrome; HIV, HIV, human immunodeficiency virus; MHC II, major histocompatibility complex II; NSAIDs, nonsteroidal anti-inflammatory drugs. Lymphocyte variant HES.…”

“…Reactive eosinophilia is predominantly mediated by IL-5 (along with IL-3 and IL-4) and is caused by atopic dermatitis, asthma and seasonal allergic disorders (rhinitis/hay fever), dermatological disorders like Wells syndrome (nonallergic granulomatous dermatitis), druginduced (includes drug reaction with eosinophilia and systemic symptoms/DRESS), helminthic and fungal infections, primary gastrointestinal eosinophilic disorders, connective tissue disorders, rheumatological diseases, atheroembolic disease, Gleich syndrome, lymphoproliferative disorders, solid malignancies, and the lymphocytic variant of HE. The major secondary causes [7][8][9][10][11][12][13][14][15][16][17][18][19][20] are summarized in ►Table 1.…”