Association Between Immune-related Adverse Events and Clinical Outcome Following Nivolumab Treatment in Patients With Metastatic Renal Cell Carcinoma

Abstract

Background/Aim: Immune-related adverse events (irAEs) are associated with the efficacy of immune-checkpoint inhibitors in patients with melanoma and non-small cell lung cancer. We therefore evaluated the relationship between irAEs and nivolumab efficacy against metastatic renal cell carcinoma. Patients and Methods: The medical records of 53 consecutive patients were reviewed and analyzed. Results: Median overall survival was significantly better in patients who showed irAEs at any time compared to patients without irAEs (p=0.013). We identified irAEs in 24 of 53 patients (45.3%), including four patients (7.5%) with grade 3 events. Multivariate analysis also revealed that risk factors for the onset of irAEs were positively associated with a platelet-tolymphocyte ratio <156 before nivolumab treatment (p=0.006). Conclusion: Development of irAEs was associated with survival outcomes of nivolumab treated patients with metastatic renal cell carcinoma. Patients and Methods Study design. We retrospectively reviewed the medical records of all patients with mRCC who were previously treated with VEGFtargeted therapy and who started treatment with nivolumab at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research between September 2016 and September 2018. This review identified 53 eligible patients who received nivolumab monotherapy. Patients with known active or suspected autoimmune disease and patients requiring immunosuppressive medications were excluded from participation in this study. Treatment regimen and study drugs. Based on the results from a previous clinical trial (1), patients were given nivolumab every 2 weeks until the end of treatment or follow-up. In Japan, the 2647 This article is freely accessible online.

Complete response to combination therapy using nivolumab and ipilimumab for metastatic, sarcomatoid collecting duct carcinoma presenting with high expression of programmed death-ligand 1: a case report

“…Previous studies reported a relationship between irAEs and the antitumor effect of ICIs in malignant melanoma and non-small cell lung cancer, resulting in significant prolongation of OS [ 20 , 21 ]. A similar report has been published for RCC [ 22 ]. This case may also suggest an association between an irAE and complete response to nivolumab and ipilimumab.…”

Association between Immune Related Adverse Events and Outcome in Patients with Metastatic Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors

“…The correlation between irAEs and patient outcome has been recently described for different cancers [ 10 , 37 , 38 ]. The occurrence of irAEs has been found to be associated with favorable outcomes in melanoma [ 21 , 22 , 23 ], NSCLC [ 24 , 25 , 26 ] and, with only a few studies available, also in mRCC [ 27 , 28 , 29 ]. These studies corroborate the hypothesis of a direct link between antitumor response and auto-immune reactivity.…”

“…In the context of this research irAEs have been proposed as potential clinical markers to predict response to ICI. This relationship, although documented in studies regarding non-small cell lung cancer (NSCLC) and melanoma [ 21 , 22 , 23 , 24 , 25 , 26 ] has been less studied in RCC [ 27 , 28 , 29 ]. Moreover, current data on the impact of specific types of irAEs on outcomes are not entirely consistent.…”

Treatment- and immune-related adverse events of immune checkpoint inhibitors in esophageal or gastroesophageal junction cancer: A network meta-analysis of randomized controlled trials

“…It should be pointed out from the results of our meta-analysis that, although ICIs increased the adverse events, the rates were actually low and acceptable. Although immunotherapy had increased the rates of irAEs, to a certain extent, the occurrence of immune-related events may be positively correlated with the therapy’s efficacy and the patient’s prognosis ( 66 , 67 ). When focusing on the anti-tumor effects of ICIs, we should also pay attention to the occurrence of irAEs when ICIs are applied ( 68 ).…”