BackgroundInflammation may play an important role in cancer progression, and a higher systemic immune-inflammation index (SII) has been reported to be a poor prognostic marker in several malignancies. However, the results of published studies are inconsistent.Materials and MethodsA systematic review of databases was conducted to search for publications regarding the association between blood SII and clinical outcome in solid tumors with a date up to February 12, 2017. The primary outcome was overall survival (OS) and the secondary outcomes were progression-free survival (PFS) and cancer-specific survival (CSS). Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were used to assess the strength of the association between blood SII and clinical outcome in solid tumors.ResultsA total of 15 articles were included in the analysis. Overall, systemic immune-inflammation index greater than the cutoff predicted poor overall survival (HR = 1.55, 95% CI = 1.27–1.88; P < 0.001). Subgroup analyses revealed that high systemic immune-inflammation index indicated a worse overall survival in hepatocellular carcinoma (P < 0.001), urinary cancers (P < 0.001), gastrointestinal tract cancers (P = 0.02), small cell lung cancer (P < 0.05) and acral melanoma (P < 0.001). Hazard ratio for systemic immune-inflammation index greater than the cutoff for cancer-specific survival was 1.44 (P < 0.05).ConclusionsElevated systemic immune-inflammation index is associated with a worse overall survival in many solid tumors. The systemic-inflammation index can act as a powerful prognostic indicator of poor outcome in patients with solid tumors.

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Background:Baricitinib (bari), is an oral, selective inhibitor of Janus kinase (JAK) 1/JAK 2, to treat moderately to severely active RA in adults.Objectives:To update bari’s safety profile with data from an additional Phase (Ph) 3 trial and on-going long-term extension (LTE) study.Methods:Long-term safety of once-daily bari was evaluated in the All-Bari-RA dataset: all patients (pts) exposed to any bari dose from 9 randomized trials (5 Ph3, 3 Ph2, 1 Ph 1b) and 1 LTE (data to 13-Feb-2018). Placebo (PBO) comparisons were evaluated to Week 24 from 7 Ph2/3 trials: pts randomized to PBO, bari 2-mg or 4-mg, with censoring at rescue/treatment switch. Dose responses were evaluated in the 2-mg/4-mg extended dataset from 4 Ph2/3 trials: pts randomized to 2- or 4-mg, LTE data included; data censored at rescue/dose change (as-treated analysis) and, due to latent period for malignancy, analyzed without censoring (as-randomized analysis). Incidence rates (IR) per 100 patient-years (PY) were calculated.Results:3770 pts received bari (10127 PYs); maximum exposure was 7 yrs (Table). No significant differences were seen for bari 4-mg vs PBO in adverse events leading to permanent drug discontinuation, death, malignancy, serious infection, or major adverse cardiovascular events. Herpes zoster IR was significantly higher for bari 4-mg vs PBO (3.8 vs 0.9) and numerically higher for bari 2-mg (3.1). IRs for deep vein thrombosis/pulmonary embolism were numerically higher in bari 4-mg vs PBO; IRs were similar by dose in 2-mg/4-mg-extended dataset. Malignancy (excluding non-melanoma skin cancer) IRs were 0.8 (2-mg) and 1.0 (4-mg; as-randomized analysis). Fewer than 1% of pts discontinued due to abnormal laboratory results.Conclusion:In this updated integrated analysis of pts with active RA exposed to bari for up to 7 yrs, across safety topics, bari maintained a safety profile similar to that previously reported1 and acceptable in the context of demonstrated efficacy.Abstract THU0078–Table 1demographicsReference:[1] Smolen JS, et al. J Rheumatol. 2019;46:7-18.Disclosure of Interests:Mark C. Genovese Grant/research support from: Sanofi/Genzyme, Genentech/Roche, RPharm, Consultant for: Sanofi/Genzyme, Genentech/Roche, RPharm, Josef S. Smolen Grant/research support from: AbbVie, Eli Lilly, Janssen, MSD, Pfizer Inc, Roche, Consultant for: AbbVie, Amgen, AstraZeneca, Astro, Celgene, Celtrion, Eli Lilly, GlaxoSmithKline, ILTOO, Janssen, Medimmune, MSD, Novartis-Sandoz, Pfizer Inc, Roche, Samsung, Sanofi, UCB, Speakers bureau: AbbVie, Amgen, AstraZeneca, Astro, Celgene, Celtrion, Eli Lilly, GlaxoSmithKline, ILTOO, Janssen, Medimmune, MSD, Novartis-Sandoz, Pfizer Inc, Roche, Samsung, Sanofi, UCB, Tsutomu Takeuchi Grant/research support from: Astellas Pharma Inc, Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Takeda Pharmaceutical Co., Ltd., AbbVie GK, Asahikasei Pharma Corp., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Eisai Co., Ltd., AYUMI Pharmaceutical Corporation, Nipponkayaku Co. Ltd., Novartis Pharma K.K., Grant/research supp...

BackgroundRecent studies have focused on the correlation between N6-methyladenosine (m6A) modification and specific tumor-infiltrating immune cells. However, the potential roles of m6A modification in the tumor immune landscape remain elusive.MethodsWe comprehensively evaluated the m6A modification patterns and tumor immune landscape of 513 clear cell renal cell carcinoma (ccRCC) patients, and correlated the m6A modification patterns with the immune landscape. The m6Ascore was established using principal component analysis. Multivariate Cox regression analysis was performed to evaluate the prognostic value of the m6Ascore.ResultsWe identified three m6Aclusters—characterized by differences in Th17 signature, extent of intratumor heterogeneity, overall cell proliferation, aneuploidy, expression of immunomodulatory genes, overall somatic copy number alterations, and prognosis. The m6Ascore was established to quantify the m6A modification pattern of individual ccRCC patients. Further analyses revealed that the m6Ascore was an independent prognostic factor of ccRCC. Finally, we verified the prognostic value of the m6Ascore in the programmed cell death protein 1 (PD-1) blockade therapy of patients with advanced ccRCC.ConclusionsThis study demonstrated the correlation between m6A modification and the tumor immune landscape in ccRCC. The comprehensive evaluation of m6A modification patterns in individual ccRCC patients enhances our understanding of the tumor immune landscape and provides a new approach toward new and improved immunotherapeutic strategies for ccRCC patients.