Joint-Predominant Rheumatic Complications of Immune Checkpoint Inhibitor Therapy in Patients with Thymic Epithelial Tumors.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced cancers. However, activation of the immune system can occasionally cause life-threatening toxicity involving critical organs. Induction of immune-mediated toxicity is a significant concern for patients with thymic epithelial tumors (TETs) due to defects in immune tolerance. An increased risk of skeletal and cardiac muscle inflammation following treatment with ICIs is well recognized in patients with advanced TETs. However, uncommon musculoskeletal and rheumatic complications can also occur. The cases presented in this report highlight the spectrum of presentation of immune-mediated, joint-predominant musculoskeletal adverse events in patients with advanced TETs treated with ICIs, including polymyalgia rheumatica-like illness and inflammatory arthritis.

Tolerability of Coronavirus Disease 2019 Vaccines, BNT162b2 and mRNA-1273, in Patients With Thymic Epithelial Tumors.

INTRODUCTION: Defects in immunologic self-tolerance result in an increased risk for development of paraneoplastic autoimmune diseases (ADs) and immune-mediated toxicity in response to immune stimulation in individuals with thymic epithelial tumors (TETs). We conducted a survey to evaluate the tolerability of coronavirus disease 2019 (COVID-19) mRNA vaccines in patients with TETs, including individuals with preexisting AD. METHODS: After reviewing published data on adverse events associated with the BNT162b2 (Pfizer, Inc., and BioNTech) and mRNA-1273 (ModernaTX, Inc.) mRNA vaccines, we designed and administered a questionnaire to participants at the following three time points: after each dose of vaccination and 1 month after the final dose. Questions related to AD and use of immunosuppressive drugs were included. Descriptive statistics were used to analyze data, and results were compared with previously described results related to the BNT162b2 and mRNA-1273 vaccines. RESULTS: From February 26 to June 1, 2021, we administered the survey to 54 participants (median age = 58 y, thymoma = 33, preexisting AD = 19). Common adverse events included injection site pain, fatigue, and headaches. There were no vaccination-related hospitalizations or deaths. Autoimmune flares occurred in three patients (16%) after the first dose and three patients (17%) after the second dose. Most AD flares were mild and self-limited. One patient (2%) was diagnosed with having a new AD after vaccination. CONCLUSIONS: Tolerability of COVID-19 mRNA vaccines in patients with TETs is comparable to the general population. Most patients with preexisting AD did not experience disease flares, and the development of new AD was rare. Patients with TETs should be encouraged to get vaccinated against COVID-19 owing to the documented benefits of vaccination and manageable risk profile.

The role of immunotherapy for management of advanced thymic epithelial tumors: a narrative review.

The emergence of immunotherapy as a modern pillar of cancer treatment has changed the treatment landscape for various cancers. Immune checkpoint inhibitors directed at programed death-1 (PD-1) or its ligand (PD-L1), in particular, have found widespread clinical applications and have resulted in durable responses and an improvement in survival of patients with advanced or metastatic disease. Tumor cell PD-L1 expression and tumor mutation burden (TMB) are biomarkers of response and efforts are underway to identify other biomarkers that might predict benefit with these drugs. Most patients tolerate immunotherapy well, although a subset of patients develop immune-mediated toxicity due to excessive immune stimulation. Thymic epithelial tumors (TETs) have a unique biology which can predispose to development of autoimmune paraneoplastic disease, especially in patients with thymoma. Due to defects in immunological self-tolerance, the use of immunotherapy in TET patients is associated with an increased risk of immune-mediated adverse events, which can be potentially life-threatening. Development of biomarkers of response and toxicity is particularly important for the treatment of TETs since it is important to identify patients who might benefit from treatment and be at low risk for development of severe immune toxicity. The use of immunotherapy in patients with autoimmune disorders and those who have previously experienced immune-mediated toxicity is currently an area of active research. Various risk mitigation strategies are under evaluation in prospective clinical trials, including trials of immune checkpoint inhibitors in patients with thymic cancers.