Isolated autoimmune adrenocorticotropic hormone deficiency: A positive predictor of survival among cancer patients treated with checkpoint inhibitors

Objective: We aimed to characterize cancer patients who developed isolated adrenocorticotrophic hormone (ACTH) deficiency (IAD) after treatment with checkpoint-inhibitors (CPIs), including clinical manifestations, laboratory findings and risk factors, and to evaluate the prognostic significance of this complication. Design: A retrospective case-control study. Methods: We conducted a retrospective analysis of 2225 cancer patients treated with CPIs between 2015 and 2021 in our institute. We identified a subgroup of patients with sub-normal cortisol levels due to ACTH deficiency, and comprehensively extracted all relevant data. We compared the patients survival rates using a log-rank test and a multi-variable Cox regression. Results: Among 2225 patients, hypocortisolemia was documented in 99 (4.45%) patients, and 19 of them were diagnosed with IAD (0.85%). Asthenia and diarrhea were the most reported complaints (36.8%), and melanoma was the most common malignancy (68.42%) within the IAD group. In multivariable analysis, IAD was associated with better survival rates (p = .018), female gender (63.2% vs 40%, p = .041), treatment with Ipilimumab (57.9% vs. 19.4%, p < .001), and younger age (median 56 IQR 51–69, vs. median 69 IQR 60–76, p = .004). Conclusions: IAD is the dominant autoimmune etiology for cortisol deficiency among patients receiving immunotherapy and is reported for the first time as a positive predictor of survival among cancer patients treated with CPIs. In our patients, IAD development was associated with female gender, treatment with ipilimumab, and younger age.