Management of immune-checkpoint inhibitor (ICI)-related thyroid dysfunction: An avenue for quality improvement.

Abstract

309 Background: Hypothyroidism is a common immune-related adverse effect (irAE) with ICI therapy, occurring in 4-9% of patients treated with PD-1 ICI, and 10-15% of patients treated with dual PD-1/CTLA-4 ICI therapy. Prolonged thyroid dysfunction increases risk for cardiovascular and cerebrovascular events. Consensus guidelines recommend weight-based dosing for thyroid repletion in younger patients and/or without cardiovascular comorbidities. We observed that patients on thyroid repletion are often underdosed compared to guideline recommendations. To formally evaluate this, we performed a retrospective study to determine the percentage of ICI-treated cancer patients who are receiving guideline-recommended thyroid repletion at an urban comprehensive cancer center. Methods: We identified patients who received PD-1 ICI, either singly or in combination with chemotherapy, TKI, or other ICI to identify patients who met the consensus guideline criteria for weight-based dosing of thyroid repletion. Analysis was restricted to ICI-treated patients who had a thyroid stimulating hormone (TSH) level above 10 mU/L following initiation of therapy. For each patient, we collected the patient’s age, weight, and initial prescribed dose of levothyroxine. We also obtained the date of abnormality and normalization for TSH and free thyroxine (T4). Results: 402 patients received ICI, either singly or in combination. 55 patients had TSH > 10 mU/L. 15 patients who did not have documentation of hypothyroidism or developed it prior to immunotherapy were excluded. The proportion of patients who were eligible for, and who received weight-based repletion is summarized in the table. The proportion of patients who received guideline-recommended thyroid repletion was: 6/17 (35%) SITC-guideline recommended dose, 18/27 (67%) NCCN-guideline recommended dose and 6/22 (28%) ASCO-guideline recommended dose. The median time to free T4 normalization was 9 weeks (IQR 6-15 weeks) and TSH normalization was 13 weeks (IQR 9-30 weeks). Conclusions: At an urban comprehensive cancer center, the incidence of hypothyroidism in ICI-treated cancer patients is 10%. The compliance with guideline recommended weight-based dosing is low, with 33-72% of patients not receiving appropriate therapy, translating into prolonged time to thyroid function normalization. We aim to develop a quality improvement intervention to improve thyroid dosing in this patient population. Proportion of patients receiving guideline-recommended thyroid repletion. Criteria Per SITC Guidelines Per NCCN Guidelines (if lower end of dosing range) Per ASCO Guidelines Patients eligible for weight-based dosing 17 27 22 # of patients who received appropriate initial dosing 6 (35%) 18 (67%) 6 (28%) Average initial dose prescribed 81 mcg 78 mcg 76 mcg Average initial dose per guidelines (based on ideal body weight) 107 mcg 71 mcg 109 mcg