Background: Immune related adverse events (iRAEs) of the endocrine system are commonly recognised in Checkpoint Inhibitor Therapy treatment with current research suggesting clinically significant endocrinopathies occur in 10%. As the use of these drugs continues to rise, so too does the importance of routine endocrine monitoring in order to avoid potentially life-threatening adverse-events.
Aims: To establish the frequency, severity, management and outcomes of endocrine IRAEs in patients undergoing Checkpoint Inhibitor therapy in our institution and to review endocrine investigations initiated. We wished to develop an appropriate algorithm for routine monitoring of these patients.
Method: Using the hospitals database, a retrospective, anonymized audit of all patients receiving immunotherapy with Ipilimumab, Pembrolizumab, Nivolumab or a combination of these agents over the period from 2013 to 2018 were identified. The incidence, grade and outcome of thyroid dysfunction, hypophysitis, primary adrenal insufficiency and insulin-deficient diabetes in this group were recorded. The frequency of monitoring of TFTs, ACTH, cortisol, blood glucose level and HbA1c was also recorded.
Results: We reviewed the records of 37 patients. Patients receiving monotherapy included 21 receiving Nivolumab, 7 receiving Pembrolizumab and 4 receiving Ipilimumab. 5 patients received combination therapy. 8 patients (22%) in total reported an Endocrine IRAE. Thyroid dysfunction occurred in 7 patients (19%). 2 of which were Grade 1, 5 were Grade 2. TFTs were recorded regularly every 2 weeks on 35/37 patients (95%). 1 patient (2.7%) was diagnosed with Cortisol Deficiency, Grade 3 and occurred with combination therapy. Cortisol was recorded on just 10 patients (27%) although 27 patients (73%) reported fatigue during the course of their treatment. Glucose recordings were taken on 13 patients (35%) with 7 patients (19%) recording hyperglycaemia. There were no cases of Insulin-Deficient Diabetes diagnosed in our group.
Conclusion: We have noted a high incidence of endocrine related IRAEs and, with one exception, patients were able to continue or to recommence therapy. As knowledge of the iRAEs increased, monitoring was more common. While comprehensive monitoring for thyroid dysfunction was performed, routine evaluation of adrenal function for primary or secondary deficiency was not. For this reason, we have developed an algorithm for monitoring which will be presented.
18 - 21 May 2019
European Society of Endocrinology