Endocrine immune-related adverse events in patients with metastatic renal and urothelial cancer treated with immune checkpoint-inhibitors

接受免疫检查点抑制剂治疗的转移性肾癌和尿路上皮癌患者的内分泌免疫相关不良事件

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Abstract

PURPOSE: To evaluate the incidence, diagnosis and treatment of immune-related adverse events (e-irAE) of checkpoint inhibition (ICI) in metastatic urothelial carcinoma (mUC) and metastatic renal cell carcinoma (mRCC). METHODS: A retrospective, single-center study was conducted to identify a cohort that received ICI for mUC or mRCC. e-irAE were classified according to the CTCAE V.5.0. Patients received ICI for mUC or mCC between 01/2017 and 03/2021. A retrospective chart review was performed. T-Test, the chi-squared test, and Fisher's exact test were performed. RESULTS: 102 Patients received ICI [mUC: 40 (39%), mRCC: 62 (61%)]. 64 (63%) received an ICI monotherapy, 27 (27%) a dual ICI therapy, 11 (11%) a combination with VEGFi. e-irAE occurred in 19 (19%) patients [grade 1-2: 17 (84%), grade 3: 3 (16%)]. The median time until e-irAE was 42 days (range 11-211 days). 14 Patients developed thyroidism (14%), 4 (4%) a hypophysitis, 1 (1%) an adrenal insufficiency (AI). 7 patients (7%) had to discontinue ICI therapy [hypophysitis (100%), AI (100%), thyroidism (14%)]. 6 (86%) received cortisone. After a median range of 34 days 5 patients (71%) restarted ICI therapy. All patients (n = 4) with hypophysitis continued ICI [4 (100%) prednisone, 3 (75%) levothyroxine]. 11 (79%) presented with hyperthyroidism. 4 (37%) needed therapy (1 (7%) prednisone, 3 (21%) thiamazole, 2 (14%) beta blocker). The 9 (64%) patients with hypothyroidism received levothyroxine. Hypophysitis appears only on dual ICI (CTLA-4/PD-1) inhibition (p 0.007). CONCLUSION: This study shows the importance of adequate diagnosis and therapy of e-irAEs.

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