Hypothyroidism related to immunotherapy in elderly adults: Analysis of a Colombian oncology cohort.

Abstract

e24109 Background: Immunotherapy, including immune checkpoint inhibitors (ICIs), is a standard treatment for various cancers and has proven effective in older adults. Although generally well-tolerated, ICIs can induce immune-related adverse events (irAEs), such as thyroid dysfunction, with an incidence ranging from 8% to 16.4%. However, their impact on older adults is underexplored. Methods: This prospective, descriptive cohort study included patients aged 65 and older undergoing immunotherapy. The primary endpoint was hypothyroidism incidence during immunotherapy. Secondary outcomes included time to onset, levothyroxine dosage, and therapeutic response. Incidence rates and cumulative incidence were calculated, and non-parametric tests evaluated statistical significance. Results: Fifty patients were included (76% male). The most common cancer types were lung (32%), renal (30%), and liver/pancreas (10%), with Pembrolizumab (65%), Nivolumab (28%), and Atezolizumab (6%) being the most frequently used treatments. Combination ICI therapy was administered to 10%. The incidence of de novo hypothyroidism in the entire cohort was 24%, with no cases of central hypothyroidism. Hypothyroidism was more common in renal (40%) and lung cancers (25%). The treatments most associated with the development of hypothyroidism were Atezolizumab (33%), Pembrolizumab (28.1%), and Nivolumab (14.3%), no cases reported in patients with ICIs combinations, although none of these associations were statistically significant. The cumulative incidence of hypothyroidism increased over time: 25% at 1 month, 41% at 2 months, 49% at 4 months, 67% at 8 months, 75% at 1 year, and 100% at 2 years, with a median time to development of hypothyroidism of 6 months. The average initial levothyroxine dose was 1.7 mcg/kg, reduced to 1.5 mcg/kg at six months, with only 50% of patients achieving therapeutic goals. The dose was then titrated to 1.7 mcg/kg at one year, with 100% reaching therapeutic targets. Conclusions: Our cohort of older adults show a trend towards a higher incidence of hypothyroidism during ICIs therapy compared to global literature reports for both elderly and younger populations. Peak incidence occurred in the first year, highlighting the need for rigorous thyroid monitoring during this period. Additionally, older adults required higher doses of levothyroxine to achieve therapeutic goals which contrasts with existing findings. These results suggest that older adults require more individualized thyroid management strategies, including closer monitoring and potential dose adjustments to optimize treatment outcomes.