BackgroundThyroid dysfunction is a well known side effect of immune checkpoint blockade (ICB) and is one of the most common causes of immune-related adverse events (IRAE). The incidence varies with each individual therapy but generally estimated to be in the range between 6–18% per one study. Hypothyroidism and thyroiditis are the most common manifestations. Initial hyperthyroidism followed by hypothyroidism is another manifestation. Hypothyroidism is more common with an incidence of 10% whereas hyperthyroidism has an incidence of 5%. Less is known about the incidence of worsening thyroid dysfunction in patients with pre-existing thyroid dysfunction treated with ICB.MethodsA retrospective analysis was collected on 370 patients who received immunotherapy from April 2015 to April 2019. Of those, 212 had abnormal thyroid function tests. We analyzed a subgroup of these patients who had baseline thyroid dysfunction for worsening thyroid dysfunction after they were given ICB. Fifty-three patients were included in the analysis and had an abnormal baseline TSH at the start of immunotherapy. Type of immunotherapy, worst TSH, duration between initiation of immunotherapy to worst TSH, treatment type, and grade of abnormality as per Immune Checkpoint Inhibitor Related Adverse Events Common Terminology Criteria for Adverse Events (IRAE-CTCAE) were also recorded. Analysis was done for patients to compare likelihood of worsening TSH resulting in change in treatment for thyroid disorder.ResultsOf the identified patients (N=53) with abnormal TSH screening values outside of the institution’s normal reference range 0.35 - 4.95 uIU/ml, 45.7% (N=16) were hypothyroid and 54.3% (N=19) were hyperthyroid at baseline. Of those who were hypothyroid, 50% (N=8) had worsening TSH and 50% (N=8) had unchanged TSH during treatment. Of those who were hyperthyroid, 31.6% (N=6) had unchanged TSH, 52.6% (N=10) had worsened TSH, and 15.8% (N=3) had normalization of TSH compared to baseline. Overall 26.4% had worsening and of those 11.3% required treatment change.ConclusionsThyroid dysfunction is one of the most common IRAE’s associated with immune checkpoint inhibitors. Little is known about the impact of immunotherapy on patients with existing thyroid dysfunction. Patients who have underlying thyroid dysfunction are at an increased risk for worsening thyroid dysfunction with the use of ICB but though not unduly above the risk general population. Of those with change, only a modest percentage required an alteration of their endocrine therapy. Of interest, our data suggests a potential increased risk in patients with baseline hyperthyroidism compared to hypothyroidism which may be clinically relevant.Ethics ApprovalThe study was approved by ECU Brody School of Medicine Institution’s Ethics Board, approval number 19-000710.ReferencesBarroso-Sousa R, Barry WT, Garrido-Castro AC, et al. Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis. JAMA oncology. 2018;4:173–182.Fessas P, Possamai LA, Clark J, et al. Immunotoxicity from checkpoint inhibitor therapy: clinical features and underlying mechanisms. Immunology. 2019; 2020;159:167–177.Brody HM, Macherla S, Bulumulle A, Namireddy P, Cherry CR. The real-world incidence of immunotherapy-related thyroid dysfunction: A retrospective analysis of a single center’s experience over five years. Journal of clinical oncology. 2020;38:98–98.Iyer PC, Cabanillas ME, Waguespack SG, et al. Immune-Related Thyroiditis with Immune Checkpoint Inhibitors. Thyroid (New York, N.Y.). 2018;28:1243–1251.Presotto EM, Rastrelli G, Desideri I, et al. Endocrine toxicity in cancer patients treated with nivolumab or pembrolizumab: results of a large multicentre study. Journal of endocrinological investigation. 2019; 2020;43:337–345.Chalan P, Di Dalmazi G, Pani F, De Remigis A, Corsello A, Caturegli P. Thyroid dysfunctions secondary to cancer immunotherapy. Journal of endocrinological investigation. 2017; 2018;41:625–638.Mangla A, Paydary K, Yadav U, Liu J, Lad TE. Predictors and outcomes of thyroid dysfunction with immunotherapy: A single institution observational experience. Journal of clinical oncology. 2019;37:e14134-e14134.Basak EA, van der Meer, Jan W M, Hurkmans DP, et al. Overt Thyroid Dysfunction and Anti-Thyroid Antibodies Predict Response to Anti-PD-1 Immunotherapy in Cancer Patients. Thyroid (New York, N.Y.). 2020;30:966–973.Kassi E, Angelousi A, Asonitis N, et al. Endocrine-related adverse events associated with immune-checkpoint inhibitors in patients with melanoma. Cancer medicine (Malden, MA). 2019;8:6585–6594.

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98 Background: Immunotherapy related thyroid abnormalities are well described. Any grade abnormality has been reported in 6-18% of patients. The clinical relevance of thyroid abnormalities in a real-world setting is still unclear. In this retrospective study, we analyzed immunotherapy type with time to thyroid dysfunction, grade of thyroid dysfunction, and number that ultimately required treatment. Methods: We retrospectively collected data for patients who received immunotherapy from April 2015 to August 2019. We recorded the type of immunotherapy, any abnormal TSH and grade of abnormality using the immune checkpoint inhibitor related adverse events Common Terminology Criteria for Adverse Events (IRAE-CTCAE), number of days from start of treatment to first noted abnormal TSH, and number requiring treatment with levothyroxine. At our large academic center, we analyze thyroid function prior to starting immunotherapy and at every treatment. Results: Of our 374 patients, 159 had some grade of thyroid dysfunction after receiving immunotherapy. Of the 159 patients with thyroid dysfunction, 23 had atezolizumab, (A), 81 had nivolumab (N), and 55 had pembrolizumab (P). Within these sub-groups, the majority of the adverse events were grade one, 74% in the A group, 57% in the N group, and 76% in the P group. Of these, zero were treated with levothyroxine. Grade two toxicities were seen in 22% in the A group, 31% in the N group, and 22% in the P group. Of these, a total of eight patient required treatment with levothyroxine. Average days to abnormal TSH was 97 in the A group, 94 in the N group, and 130 in the P group. Conclusions: In our population, 42.5% of patients had some grade of thyroid dysfunction which is higher than the previously reported values, however, the majority of abnormalities were grade one and self-resolved. This may indicate that transient changes in TSH are much more common than previously noted but not necessarily clinically relevant.

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e21047 Background: There has been prospective and retrospective evidence for the onset of immunotherapy (IO) related adverse events (irAE) and efficacy of anti programmed death (PD1) and Programmed death Ligand 1(PD L1) antibodies. The incidence of irAE in these studies ranged anywhere from 30-44%. There have been attempts in the past to cluster irAEs into distinct subtypes by T cell profiling before and after immunotherapy. Identifying the trend of CD4/CD8 changes during irAE may aid in finding ways to mitigate the severe toxicities, so the benefits of immunotherapy can be extended to far more number of patients. Methods: We have collected blood samples from 20 patients of Non Small Cell Lung Cancer patients (NSCLC) before each cycle of immunotherapy with informed consent. We have measured the different inflammatory markers such as IL6, IL10 using ELISA and isolated cellular components such as CD4, CD8 T cells along with others using magnetic bead technique, from these samples in our research laboratory at East Carolina University. We have also collected clinical information including the adverse events with their (Common Terminology Criteria for Adverse events) CTCAE 5.0 grading, different cell counts and C- reactive Protein (CRP). Results: In the cohort of 20 patients, 9 experienced irAE, out of which 6 had grade 2, including thyroiditis, pneumonitis, dermatitis, cytokine release syndrome (CRS), 1 had grade 3 pneumonitis, 1 had grade 4 pneumonitis and 1 had grade 1 CRS. When we looked at the CD4/CD8 ratio before each cycle, the one prior to the incidence of the irAE had at least 30-40% drop in the ratio consistently although there were minor fluctuations in the ratio at other times in both directions. Conclusions: Although most irAEs can be treated and reversed with steroids and other immunosuppressive agents, prolonged immunosuppression can lead to reduced efficacy of IO and development of undue opportunistic infections. Experience with IO has shown that earlier initiation of immunosuppression shortens the required treatment. However, given the challenge in the subtility of the earlier presentation, therapies are frequently delayed. Hence, biomarker to identify the early manifestations is of critical importance for early intervention. Studies suggest there is clonal expansion of CD8 T cells preceding grade 2-3 irAEs. Studies also indicate that increased T cells in the tumor is indicative of response to immunotherapy. Our observation suggests that increased CD8 in proportion to CD4 in the peripheral blood precedes the onset of irAE. It is unclear as to how this leads to increased toxicity when the immunotherapy treatment works by affecting T cell function. One possible explanation is that the T cell response in the tumor tissue is beneficial, however, T cell response in the peripheral blood may indicate response against self antigens leading to toxicities in the form of irAE.