@article{cd4d9d923fa34789b34a2519ba62ca79,
title = "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.",
keywords = "NER, eosinophil, immune checkpoint inhibitor, kidney cancer, neutrophil-to-eosinophil ratio, renal cell carcinoma",
author = "Chen, {Yu Wei} and Tucker, {Matthew D.} and Brown, {Landon C.} and Yasin, {Hesham A.} and Ancell, {Kristin K.} and Armstrong, {Andrew J.} and Beckermann, {Kathryn E.} and Davis, {Nancy B.} and Harrison, {Michael R.} and Kaiser, {Elizabeth G.} and McAlister, {Renee K.} and Schaffer, {Kerry R.} and Wallace, {Deborah E.} and George, {Daniel J.} and Rathmell, {W. Kimryn} and Rini, {Brian I.} and Tian Zhang",
note = "Funding Information: This research was supported by the NIH T32 Training Program in Molecular and Genetic Epidemiology (T32 CA160056). Funding Information: YWC: has provided consulting for Deloitte and holds stock in Biogen (an immediate family member). LCB: has provided consulting for Seattle Genetics and Astellas. AJA has received research funding to his institution from Dendreon, Bayer, Pfizer, Novartis, Janssen Oncology, Astellas Pharma, Gilead Sciences, Roche/Genentech, Bristol-Myers Squibb, Constellation Pharmaceuticals, Merck, AstraZeneca, BeiGene, Amgen, and Forma Therapeutics and consulting fees from Bayer, Dendreon, Pfizer, Astellas, AstraZeneca, Merck, Bristol-Myers Squibb, Janssen, FORMA Therapeutics, Novartis, Exelixis, Myovant Sciences, and GoodRx, as well as travel support from Astella Scientific and Medical Affairs, Inc. He has received patents to his institution for circulating tumor cell novel capture technology. KEB has received research funding to her institution from Bristol-Myers Squibb and Merck Sharp & Dohme, as well as consulting fees from Aravive, Exelixis, Bristol-Myers Squibb and Seattle Genetics. NBD has received research funding to her institution from AstraZeneca, Roche, Pfizer, Merck, Incyte, Mirati Therapeutics, Seattle Genetics/Astellas, Calithera Biosciences, Immunomedics, Bristol-Myers Squibb, Exelixis, and Gilead Sciences and consulting fees from Janssen Biotech. MRH has received research funding to his institution from Bristol-Myers Squibb, Genentech, Pfizer, Merck, Astellas Pharma, Bayer, Exelixis, Seattle Genetics, and Propella Therapeutics, as well as consulting fees from Exelixis, Fujifilm, Pfizer, Bristol-Myers Squibb, Seattle Genetics, Gilead Sciences, and Myovant Sciences. He is also on the speaker{\textquoteright}s bureau for Exelixis, Eisai, Gilead Sciences, and Myovant Sciences. RKM: has received consulting fees from Immunocore, Sanofi/Regeneron, and Myovant Sciences. KRS has received researching funding to her institution from Tempus and consulting fees from Janssen Biotech. DJG has received research funding to his institution from Exelixis, Janssen Oncology, Novartis, Pfizer, Astellas Pharma, Bristol-Myers Squibb, Acerta Pharma, Bayer, Dendreon, Innocrin Pharma, Calithera Biosciences, and Sanofi/Aventis; consulting fees from Bayer, Exelixis, Pfizer, Sanofi, Astellas Pharma, Innocrin Pharma, Bristol-Myers Squibb, Genentech, Janssen, Merck Sharp & Dohme, Myovant Sciences, AstraZeneca, Michael J. Hennessy Associates, Constellation Pharmaceuticals, Physician{\textquoteright}s Education Resources, Propella Therapeutics, RevHealth, and xCures; honoraria from Sanofi, Bayer, Exelixis, EMD Serono, OncLive, Pfizer, UroToday, Acceleron Pharma, the American Association for Cancer Research, Axess Oncology, Janssen Oncology, and Millennium Medical Publishing; travel support from Bayer, Exelixis, Merck, Pfizer, Sanofi, Janssen Oncology, UroToday; and is connected to the leadership of Capio Biosciences. WKR has received research funding to her institution from Peloton Therapeutics, Incyte (an immediate family member) and Sitryx (an immediate family member); consulting fees from Sitryx (an immediate family member), Nirojy (an immediate family member), and Caribou Biosciences (an immediate family member); honoraria from Pfizer (an immediate family member); patents for ClearCode34 Risk prediction biomarker for kidney cancer, hERV 3-2 expression as a biomarker of response to immunotherapy; she holds stock in Sitryx (an immediate family member), Caribou Biosciences (an immediate family member), and Nirogy Therapeutics (an immediate family member). BIR has received research funding to his institution from Pfizer, Roche/Genentech, Bristol-Myers Squibb, Merck, AstraZeneca/MedImmune, Incyte, Arrowhead Pharmaceuticals, Taris, Seattle Genetics, Immunomedics, Surface Oncology, Dragonfly Therapeutics, Aravive, and Exelixis; consulting fees from Pfizer, Merck, Synthrox, Bristol-Myers Squibb, AVEO, Surface Oncology, 3D Medicines, Corvus Pharmaceuticals, Aravive, Arrowhead Pharmaceuticals, Shionogi, Eisai, and GlaxoSmithKline; travel support from Pfizer, Bristol-Myers Squibb, and Merck; is connect to the leadership of MJH Life Sciences, and holds stock in PTC Therapeutics. TZ has received research funding to her institution from Janssen, Pfizer, Merrimack, Stem CentRx, Novartis, OmniSeq, Personal Genome Diagnostics, Regeneron, Merck, Mirati Therapeutics, Loxo/Lilly, and Astellas Pharma; consulting fees from Janssen, Exelixis, Pfizer, Bristol-Myers Squibb, Merck, Seattle Genetics, Dendreon, Calithera Biosciences, QED Therapeutics, Eisai, Aravive, Lilly, AVEO, Merck and Bayer; honoraria from MJH Life Sciences, Pacific Genuity, Aptitude Health, Peerview, Clinical Care Options, and Curio Science; serves on the speaker{\textquoteright}s bureau to Genomic Health and Sanofi/Aventis; her institution holds patents for circulating tumor cell novel capture by c-MET technology, and prochelators as targeted prodrugs for prostate cancer; and is connected to the leadership of Capio Biosciences (an immediate family member) and Archimmune Therapeutics (an immediate family member). The remaining authors declare that they have no competing interests. Publisher Copyright: {\textcopyright} 2022 by the authors.",
year = "2022",
month = aug,
doi = "10.3390/cancers14153830",
language = "English (US)",
volume = "14",
journal = "Cancers",
issn = "2072-6694",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "15",
}