The Association between a Decrease in On-Treatment Neutrophil-to-Eosinophil Ratio (NER) at Week 6 after Ipilimumab Plus Nivolumab Initiation and Improved Clinical Outcomes in Metastatic Renal Cell Carcinoma

Abstract

A lower baseline neutrophil-to-eosinophil ratio (NER) has been associated with improved responses to immune checkpoint inhibitors (ICI)-treated metastatic renal cell carcinoma (mRCC). This study investigated the decrease in NER at week 6 after ipilimumab/nivolumab (ipi/nivo) initiation and treatment responses in mRCC. A retrospective study of ipi/nivo-treated mRCC at two US academic cancer centers was conducted. A landmark analysis at week 6 was performed to assess the association between the change in NER and clinical responses (progression-free survival (PFS)/overall survival (OS)). Week 6 NER was modeled as a continuous variable, after log transformation (Ln NER), and a categorical variable by percent change. There were 150 mRCC patients included: 78% had clear cell histology, and 78% were IMDC intermediate/poor risk. In multivariable regression analysis, every decrease of 1 unit of Ln NER at week 6 was associated with improved PFS (adjusted hazard ratio (AHR): 0.78, p-value:0.005) and OS (AHR: 0.67, p-value: 0.002). When NER was modeled by percent change, decreased NER > 50% was associated with improved PFS (AHR: 0.55, p-value: 0.03) and OS (AHR: 0.37, p-value: 0.02). The decrease in week 6 NER was associated with improved PFS/OS in ipi/nivo-treated mRCC. Prospective studies are warranted to validate NER change as a biomarker to predict ICI responses.

Eosinophil may be a predictor of immune‐related adverse events induced by different immune checkpoint inhibitor types: A retrospective multidisciplinary study

“…Therefore, several studies have shown that an increase in eosinophil is a biomarker of irAEs occurences 17–20 . Although the detailed underlying mechanisms about association between eosinophils and irAEs occurrence are unclear, previous studies supported our data that increased eosinophils may reflect efficacy and safety in patients treated with ICIs 16,18,24–27,38 …”

“…[17][18][19][20] Although the detailed underlying mechanisms about association between eosinophils and irAEs occurrence are unclear, previous studies supported our data that increased eosinophils may reflect efficacy and safety in patients treated with ICIs. 16,18,[24][25][26][27]38 In the past, most studies have shown that ICImediated irAEs may be associated with an improved response to therapy and survival outcomes in several types of cancers. [43][44][45][46] Consistently, our data revealed significantly longer mOS and mPFS in patients with irAEs than in those without irAEs, as reported in another study (Figure 4A,B).…”

“…Our data indicated that incidents of irAEs might be different among cancer type. The efficacy of ICIs has been reported to be related to irAEs occurrences and tumor mutational burden (TMB) 16,24–29 . Melanoma have the highest rate of TMB ≥ 10 mutation/Mb 28 .…”

“…The efficacy of ICIs has been reported to be related to irAEs occurrences and tumor mutational burden (TMB). 16 , 24 , 25 , 26 , 27 , 28 , 29 Melanoma have the highest rate of TMB ≥ 10 mutation/Mb. 28 The urothelial carcinoma and gastrointestinal cancer treated with anti‐PD‐1 monotherapy have lower TMB ≥ 10 mutation/M than melanoma, lung cancer, and head and neck cancer.…”

Identification of berberine as a potential therapeutic strategy for kidney clear cell carcinoma and COVID-19 based on analysis of large-scale datasets

“…KIRC patients with a high immune score were at increased risk, suggesting KIRC progressed when a significant proportion of immune cells were concentrated in the tumour microenvironment (TME). In recent years, immune checkpoint inhibitors have gradually become a mainstream therapy and research focus for KIRC ( 78 ) and are beneficial for improving the prognosis of patients ( 79 – 81 ). Relative to chemotherapy, treatment with immune checkpoint inhibitors does not appear to significantly increase risk of serious adverse events in COVID-19-positive patients ( 82 ).…”