Immune complexome analysis of serum samples from non-small-cell lung cancer patients identifies predictive biomarkers for nivolumab therapy.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have achieved important outcomes in cancer treatment. However, current clinical biomarker tests are not suitable for some patients because they require tumor tissues and have poor predictive value for treatment responses. Therefore, the identification of biomarkers that enable screening tests in all patients is necessary. METHODS: We performed an immune complexome analysis of non-small cell lung cancer patients treated with nivolumab to comprehensively identify and compare antigens incorporated into immune complexes (IC-antigens) in serum samples from the responders (n = 15) and non-responders (n = 20). Additionally, combinations of IC-antigens characteristic to the responder group were evaluated by logistic regression analysis and receiver operating characteristics curves to examine their predictiveness for ICI treatment responses. RESULTS: The combination of predictive biomarkers detected before treatment was profilin-1, purine nucleoside phosphorylase, alpha-enolase, and nucleoside diphosphate kinase A [p = 0.0043, odds ratio = 2.26, 95% confidence interval (CI) = 1.19-4.28, area under the curve = 0.76]. The combination of predictive biomarkers detected after treatment was peptidyl-prolyl cis-trans isomerase A, ubiquitin-like modifier-activating enzyme 1, complement component C8 beta chain, and apolipoprotein L1 (p = 0.0039, odds ratio = 2.56, 95% CI = 1.25-5.23, area under the curve = 0.77). CONCLUSION: Combinations of serum IC-antigens may predict the therapeutic effect of nivolumab in non-small cell lung cancer patients.

Predictors for Diarrhea After Administration of Naldemedine: Analysis Focusing on the Administration Period of Opioid Analgesics Before the Start of Naldemedine

Purpose: Naldemedine is a peripheral µ-opioid receptor antagonist, including the treatment of opioid-induced constipation (OIC) . However, diarrhea is known as its side effect. We conducted a study focusing on the administration period of opioid analgesics before the start of naldemedine to clear predictors of diarrhea due to Naldemedine. Method: All data were retrospectively collected from the electronic medical record system. We investigated patients who initially administrated naldemedine at Nagasaki University Hospital from June 1 2017 to March 31 2019. Result: One hundred thirty-two patients were subject of investigation. The incidence of diarrhea was 25.0%. The result of the multivariate analysis showed that significant predictors of diarrhea were associated with the opioid analgesics usage period longer than 7 days before naldemedine initiation (odds ratio: 3.76, 95% confidence interval: 1.53-9.20, p=0.004). Discussion: When naldemedine was used for OIC, diarrhea may be avoided by using within 7 days after opioid analgesics.