Clinical Characters And Influence Factors Of Immune Checkpoint Inhibitor Related Thyroid Dysfunction

Objective:In recent years,there has been an increase in the use of immune checkpoint inhibitors(ICIs)for the treatment of malignant tumors.This immune-oriented approach has brought hope to more cancer patients.However,their use is associated with unique immune-related adverse effects(ir AEs).Most commonly,ir AEs involve the endocrine organs and especially immune thyroid dysfunction.However,there have been few studies examining the clinical characteristics and risk factors for such thyroid dysfunction.In this study,we aimed to examine the clinical characteristics and risk factors in a real-world immune thyroid dysfunction population.Methods:This retrospective study analyzed 439 patients from the Second Affiliated Hospital of Nanchang University from 2019 to 2022 who received ICI therapy and met our inclusion criteria.Based on their clinical presentation,participants were enrolled either in the thyroid dysfunction group(TD;n=213)or the non-thyroid dysfunction group(n=226).To describe the clinical features and the prognosis of ICI-associated thyroid dysfunction,we tested between-group differences in age,sex,body mass index,underlying disease history,baseline TSH,tumor type,previous treatment history,and immune checkpoint inhibitor type.We estimated the association between immune thyroid dysfunction and risk factor variables by calculating odds ratios.Result:1.Among the 439 participants,213(48.52%)had TD,which included 64 cases of hyperthyroidism(30.0%),10 cases of subclinical hyperthyroidism(4.8%),52 cases of hypothyroidism(24.4%),and 87 cases of subclinical hypothyroidism(40.8%).2.TD participants were younger and had higher baseline TSH levels than non-TD participants.Females who had been treated with molecularly targeted agents had a higher incidence of TD.We found that there were significant differences in the incidence of TD among the 6 types of ICIs;nivolumab had the lowest incidence(18.2%)and camrelizumab had the highest(58.3%).3.Among the 213 participants with TD,204(95.8%)had grade 1 or 2 thyroid dysfunction,9(4.2%)had grade 3 AEs,and none had grade 4 effects.Most presented with mild symptoms.Following treatment,most participants experienced a remission of clinical symptoms that did not require the suspension of ICI treatment.4.The median time of TD occurrence after ICI was 68.5 days(11–568d).The median time to develop hyperthyroidism was 66.5 days,whereas the median time to hypotheroidism was 78 days.5.Thirty three(52%)of 64 TD patients with hyperthyroidism developed hypothyroidism with a course similar to that of thyroiditis with transient hyperthyro idism.6.Among the TD group,69 were tested for thyroid-associated autoantibodies(TMAb,TGAb)which were found to be present in 27(39.1%)individuals.7.The association of immune thyroid dysfunction is an indicator of a pos-itive prognosis in patients treated with ICIs.Conclusion:1.We conclude that the association of immune thyroid dysfunction is an indicator of positive prognosis in patients treated with ICIs.We showed that,in our patient population,there was a higher incidence of ICI-related thyroid dysfunction than has been reported in clinical trials.The incidence of grade 3 or higher severity adverse events was low.Most individuals had mild symptoms that were relieved by levothyroxine hormone replacement therapy,which did not require the suspension of ICI therapy.2.Compared with the non-TD group,TD individuals were younger and had higher baseline TSH.Females who had been previously treated with molecularly targeted agents showed a higher incidence of TD.3.There were differences in TD incidence between the 6 types of ICIs;the highest was associated with camrelizumab and the lowest with nivolumab.Time to onset of abnormal thyroid function was typically in the range of 2-3months after ICI treatment.4.The median survival time was significantly longer in patients with immune TD compared with those without TD.