Incidence, features, and prognosis of immune-related adverse events involving the thyroid gland induced by nivolumab

Abstract

Background Blocking the PD-1 pathway induces immune-related adverse events (irAEs) which often involve the thyroid gland (thyroid irAEs). Clinical features of a thyroid irAE including its predictability and relationship to prognosis remain to be elucidated. Methods Two hundred consecutive patients treated with nivolumab at Kyoto University Hospital between September 1, 2014 and August 31, 2017 were included in a retrospective cohort study. We systematically determined and classified subclinical and overt thyroid irAEs based on data collected of serum free T4 and TSH levels. Baseline characteristics and detailed clinical data were analyzed, and analyses of overall survival (OS) excluded patients censored within 1 month from the first administration of nivolumab. Results Sixty-seven patients (33.5%) developed thyroid irAEs and these were divided into a subclinical thyroid irAE group ( n = 40, 20.0%) and an overt thyroid irAE group ( n = 27, 13.5%). Patients with thyroid uptake of FDG-PET before treatment showed high incidences of overt thyroid irAE (adjusted odds ratio 14.48; 95% confidence interval [CI] 3.12–67.19), while the same relationship was not seen with subclinical thyroid irAE. Regarding the total cohort, the thyroid irAE (+) group had a significantly longer median OS than the thyroid irAE (−) group (16.1 versus 13.6 months, hazard ratio [HR] 0.61; 95% CI 0.39–0.93). In 112 non-excluded patients with lung cancer, the thyroid irAE (+) group similarly had a longer median OS than the thyroid irAE (−) group (not reached versus 14.2 months, HR 0.51; 95% CI 0.27–0.92). However, this observation was not seen in 41 non-excluded patients with malignant melanoma (12.0 versus 18.3 months, HR 1.54; 95% CI 0.67–3.43). Conclusions By thyroid uptake of FDG-PET, overt thyroid irAEs could be predicted before nivolumab therapy. Thyroid irAEs related to good prognosis in lung cancer but might be inconclusive in malignant melanoma.

Multiple immune-related adverse events and anti-tumor efficacy: real-world data on various solid tumors

“…Further, patients with any irAE showed longer OSs than those without irAEs [17]. Of note, we found no specific irAE type being associated with longer survival, contrary to some reported results [26,27]. Thus, more clinical evidence is required to elucidate the association mechanisms between irAEs and ICIs efficacy.…”

Comprehensive research on thyroid diseases associated with autoimmunity: autoimmune thyroid diseases, thyroid diseases during immune-checkpoint inhibitors therapy, and immunoglobulin-G4-associated thyroid diseases

“…In the case, eosinophilia, thrombocytopenia, ESR/CRP/LDH elevation, and liver dysfunction might be important for early detection of thyrotoxicosis. Yamauchi, et al reported that patients with thyroid uptake of FDG-PET before nivolumab therapy showed high incidences of overt thyroid irAE [34]. Routine check-up of those predictive factors for thyroid irAE as well as serum FT3, FT4 and TSH levels are recommended.…”

“…If anti-tumor therapy is effective, continuation of ICI treatment is warranted with proper management of thyroid irAE [32]. In addition, development of thyroid irAE was reported to have positive correlation with feasible outcome of lung cancer [34]. In the future, identification of individuals who are susceptible to thyroid irAEs is necessary (age, gender, genetic predispositions such as HLA and immune-checkpoint molecules).…”

Are immune-related adverse events associated with the efficacy of immune checkpoint inhibitors in patients with cancer? A systematic review and meta-analysis

“…A number of recent studies has supported this hypothesis by showing favorable outcomes for patients with non-small cell lung cancer (NSCLC) and melanoma who developed various irAEs in response to immune checkpoint inhibition [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. However, a definite conclusion has not been drawn based on the findings from each single study, as contradictory results exist [23][24][25][26][27][28][29][30][31][32][33][34][35].…”