1153P - Incidence and characteristics of immunotherapy related adrenal insufficiency in a monocenter, pan-cancer cohort of 4314 patients

Background

The rapidly developing field of immune checkpoint inhibitors (ICI) necessitates insights in long-term adverse events (AE), like ICI related adrenal insufficiency (irAI). In meta-analyses of clinical trials, primary AI (PAI) incidence is likely overestimated (4-7% for combination ICI), as PAI and secondary AI (SAI) are rarely distinguished.

Methods

In this monocenter, pan-cancer retrospective analysis, patients with a single malignancy who received anti-PD-(L)1 and/or anti-CTLA-4 therapy before September 10^th 2021 and received (hydro/fludro)cortisone were identified. irAI was considered when AI was diagnosed in the absence of adrenal metastases, -surgery, -radiotherapy and long-term corticosteroid use. Diagnosis of PAI was based on cortisol <13 μmol/l and ACTH >60 ng/l, synacthen test and/or presence of mineral-corticoid dysfunction. SAI was diagnosed when ACTH <60 ng/l with low cortisol or in case of confirmed hypophysitis. Other irAI cases were labeled as unknown origin.

Results

Of 4314 patients with ICI, 160 (3.7%) developed irAI, consisting almost exclusively of SAI (3.1%) rather than PAI (0.05%, P<.001). irAI incidence was significantly higher for combination treatment versus anti-PD-(L)1 monotherapy (OR 4.95, 95% CI 3.55-6.97, p<.001). SAI presented as hypophysitis in 38% and as isolated adrenal deficiency in 62% of cases. Age, gender, metastatic status of the malignancy, history of endocrine or autoimmune disorder and other grade 3-4 AEs did not differ between PAI and SAI, or hypophysitis and IAD cases. Table: 1153P

Incidence of immunotherapy related adrenal insufficiency

Conclusions

In contrast to what is suggested in trials, ICI-induced primary adrenal insufficiency was extremely rare in this real-world analysis, while secondary adrenal insufficiency was dominantly prevalent. Combination therapy leads more frequently to irAI. In conclusion, an improved understanding of irAI is needed, which may lead to improved diagnosis, and is essential for the development of predictive biomarkers.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

E. Kapiteijn: Financial Interests, Institutional, Advisory Board: BMS, Novartis, Pierre Fabre, Merck, Delcath, Bayer, Lilly; Financial Interests, Institutional, Coordinating PI: BMS, Pierre Fabre, Delcath. C.U. Blank: Financial Interests, Institutional, Advisory Board: BMS, MSD, Roche, Novartis, GSK, AZ, Pfizer, Lilly, GenMab, Pierre Fabre; Financial Interests, Personal, Advisory Board: Third Rock Ventures; Financial Interests, Personal, Stocks/Shares: Immagene; Financial Interests, Institutional, Coordinating PI: NanoString, BMS, Novartis, 4SC; Financial Interests, Personal, Stocks/Shares, intention to develop IFN signature algorithm: NewCo, no name yet; Other, pending patent: WO 2021/177822 A1. All other authors have declared no conflicts of interest.