Baseline CRP Research Articles

THU0196 TOFACITINIB IN PATIENTS WITH RHEUMATOID ARTHRITIS AND INDICATIVE OF DEPRESSION AND/OR ANXIETY: A POST HOC ANALYSIS OF PHASE 3 AND PHASE 3B/4 CLINICAL TRIALS

Background:Depression/anxiety are common in RA pts. SF-36 MCS ≤38 can identify probable major depressive disorder and/or probable generalised anxiety disorder (pMDD/pGAD) in RA pts. Tofacitinib is an oral JAK inhibitor for the treatment of RA.Objectives:To assess pMDD/pGAD prevalence in the tofacitinib RA program and efficacy by baseline (BL) pMDD/pGAD status.Methods:Data from pts receiving tofacitinib, ADA, or PBO were pooled from 5 Phase (P)3 and 1 P3b/4 trials. Demographics/BL characteristics were reported by BL pMDD/pGAD (SF-36 MCS ≤38, presence; >38, absence). Month (M)3/6/9/12 SF-36 MCS change from BL (Δ) was estimated, and % with pMDD/pGAD reported. M3/6/12 efficacy outcomes compared tofacitinib-treated pts by BL pMDD/pGAD.Results:BL pMDD/pGAD was seen in 44.5% (tofacitinib 5 mg BID), 39.8% (tofacitinib 10 mg BID), 45.4% (ADA 40 mg Q2W) and 39.1% (PBO) of pts. pMDD/pGAD pts had higher BL CRP and worse disability, fatigue, pain and sleep vs pts without. SF-36 MCS increases were greater for tofacitinib vs PBO/ADA (Fig 1a). The % of pts with BL pMDD/pGAD who continued to have pMDD/pGAD reduced over time, and was generally lower for tofacitinib vs PBO/ADA (Fig 1b). Regardless of BL pMDD/pGAD, efficacy was generally similar for tofacitinib 5 mg BID (Table) and 10 mg BID.Conclusion:~40% of RA pts had BL pMDD/pGAD. SF-36 MCS improvements were greater for tofacitinib vs PBO/ADA. With tofacitinib, % of pts with SF-36 MCS ≤38 reduced by ~60% at M12. Tofacitinib efficacy was similar in pts with/without BL pMDD/pGAD. Limitations include using SF-36 MCS to identify probable rather than confirmed MDD or GAD. Future research using gold standard psychiatric interviews to validate use of SF-36 MCS ≤38 is needed.Table.M3/6/12 efficacy with tofacitinib 5 mg BID, by BL pMDD/pGADaSF-36 MCS ≤38SF-36 MCS >38OR (95% CI)P valueACR20 (%)b,cM355.157.90.89 (0.74, 1.08)0.2330M661.762.80.96 (0.79, 1.16)0.6511M1258.458.60.99 (0.80, 1.22)0.9279ACR50 (%)b,cM325.929.20.85 (0.70, 1.03)0.1022M636.038.00.92 (0.76, 1.11)0.3724M1233.834.30.98 (0.80, 1.20)0.8366ACR70 (%)b,cM310.111.00.91 (0.69, 1.18)0.4704M616.516.51.00 (0.79, 1.26)0.9901M1218.317.51.06 (0.83, 1.34)0.6560DAS28-4(ESR)<2.6 (%)b,cM35.47.40.72 (0.49, 1.05)0.0872M65.98.50.68 (0.49, 0.94)0.0199*M128.011.90.64 (0.47, 0.89)0.0073**ΔHAQ-DI, LS meanc,dSF-36 MCS ≤38SF-36 MCS >38Difference (95% CI)P valueM3-0.41-0.430.01 (-0.04, 0.06)0.6008M6-0.49-0.48-0.01 (-0.06, 0.04)0.6617M12-0.52-0.52-0.01 (-0.06, 0.05)0.8475*p<0.05; **p<0.01 Data pooled from 5 P3 and 1 P3b/4 tofacitinib trialsaBL pMDD/pGAD = SF-36 MCS ≤38;bLogistic regression fit;cFor PBO pts advancing to tofacitinib post-M3, only PBO data were included;dMixed-effects linear model fitΔ, change from baseline; ACR, American College of Rheumatology; BID, twice daily; BL, baseline; CI, confidence interval; DAS28-4(ESR), Disease Activity Score in 28 joints, erythrocyte sedimentation rate; HAQ-DI, Health Assessment Questionnaire-Disability Index; LS, least squares; M, month; MCS, Mental Component Summary score; OR, odds ratio; P, Phase; pGAD, probable generalised anxiety disorder; PBO, placebo; pMDD, probable major depressive disorder; pt, patient; RA, rheumatoid arthritis; SF-36, Short Form-36 health surveyAcknowledgments:Study sponsored by Pfizer Inc. Medical writing support was provided by Sarah Piggott of CMC Connect and funded by Pfizer Inc.Disclosure of Interests:Gustavo Citera Grant/research support from: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Consultant of: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Rakesh Jain Grant/research support from: Allergan, Eli Lilly, Lundbeck, Otsuka, Pfizer Inc, Shire and Takeda, Consultant of: Acadia, Alfasigma, Allergan, Eisai, Eli Lilly, Evidera, Impel, Janssen, Lundbeck, Merck, Neos Therapeutics, Neurocrine Biosciences, Osmotica, Otsuka, Pamlab, Pfizer Inc, Shire, Sunovion, Supernus, Takeda and Teva, Speakers bureau: Alkermes, Allergan, Eli Lilly, Janssen, Lundbeck, Merck, Neos Therapeutics, Neurocrine, Otsuka, Pamlab, Pfizer Inc, Shire, Sunovion, Takeda, Teva and Tris Pharmaceuticals, Fedra Irazoque-Palazuelos Consultant of: Bristol-Myers Squibb, Janssen, Pfizer Inc, Roche and UCB, Renato Guzman: None declared, Hugo Madariaga: None declared, David C Gruben Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Lisy Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Lori Stockert Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Ming-Ann Hsu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Karina Santana Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Abbas Ebrahim Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Dario Ponce de Leon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

Profiling COVID-19 pneumonia progressing into the cytokine storm syndrome: Results from a single Italian Centre study on tocilizumab versus standard of care.

Approximately 5% of patients with coronavirus disease 2019 (COVID-19) develop a life-threatening pneumonia that often occurs in the setting of increased inflammation or "cytokine storm". Anti-cytokine treatments are being evaluated but optimal patient selection remains unclear, and the aim of our study is to address this point. Between February 29 to April 6, 2020, 111 consecutive hospitalized patients with COVID-19 pneumonia were evaluated in a single centre retrospective study. Patients were divided in two groups: 42 severe cases (TOCI) with adverse prognostic features including raised CRP and IL-6 levels, who underwent anti-cytokine treatments, mostly tocilizumab, and 69 standard of care patients (SOC). In the TOCI group, all received anti-viral therapy and 40% also received glucocorticoids. In TOCI, 62% of cases were ventilated and there were three deaths (17.8 ± 10.6 days, mean follow up) with 7/26 cases remaining on ventilators, without improvement, and 17/26 developed bacterial superinfection. One fatality occurred in the 15 TOCI cases treated on noninvasive ventilation and one serious bacterial superinfection. Of the 69 cases in SOC, there was no fatalities and no bacterial complications. The TOCI group had higher baseline CRP and IL-6 elevations (p < 0.0001 for both) and higher neutrophils and lower lymphocyte levels (p = 0.04 and p = 0.001, respectively) with the TOCI ventilated patients having higher markers than non-ventilated TOCI patients. Higher inflammatory markers, more infections and worse outcomes characterized ventilated TOCI cases compared to ward based TOCI. Despite the confounding factors, this suggests that therapy time in anti-cytokine randomized trials will be key.

PTSD and the klotho longevity gene: Evaluation of longitudinal effects on inflammation via DNA methylation

BackgroundLongevity gene klotho (KL) is associated with age-related phenotypes including lifespan, cardiometabolic disorders, cognition, and brain morphology, in part, by conferring protection against inflammation. We hypothesized that the KL/inflammation association might be altered in the presence of psychiatric stress and operate via epigenetic pathways. We examined KL polymorphisms, and their interaction with posttraumatic stress disorder (PTSD) symptoms, in association with KL DNA methylation in blood. We further examined KL DNA methylation as a predictor of longitudinal changes in a peripheral biomarker of inflammation (C-reactive protein; CRP). MethodsThe sample comprised 309 white non-Hispanic military veterans (93.5 % male; mean age: 32 years, range: 19–65; 30 % PTSD per structured diagnostic interview); 111 were reassessed approximately two years later. ResultsAnalyses revealed a methylation quantitative trait locus at rs9527025 (C370S, previously implicated in numerous studies of aging) in association with a Cytosine-phosphate-Guanine site (cg00129557; B = −.65, p = 1.29 X 10−20), located within a DNase hypersensitivity site in the body of KL. There was also a rs9527025 x PTSD severity interaction (B = .004, p = .035) on methylation at this locus such that the minor allele was associated with reduced cg00129557 methylation in individuals with few or no PTSD symptoms while this effect was attenuated in those with elevated levels of PTSD. Path models revealed that methylation at cg00129557 was inversely associated with CRP over time (B = −.14, p = .005), controlling for baseline CRP. There was also an indirect effect of rs9527025 X PTSD on subsequent CRP via cg00129557 methylation (indirect B = −.002, p = .033). ConclusionsResults contribute to our understanding of the epigenetic correlates of inflammation in PTSD and suggest that KL methylation may be a mechanism by which KL genotype confers risk vs. resilience to accelerated aging in those experiencing traumatic stress.

Sarilumab and adalimumab differential effects on bone remodelling and cardiovascular risk biomarkers, and predictions of treatment outcomes

BackgroundInterleukin-6 (IL-6) is a pleiotropic cytokine that plays a key role in the pathogenesis of rheumatoid arthritis. Sarilumab is a human monoclonal antibody that binds membrane-bound and soluble IL-6 receptor-α to inhibit IL-6 signalling. The aim of this study was to compare the effects of sarilumab and adalimumab (a tumour necrosis factor alpha inhibitor) monotherapy on levels of circulating biomarkers associated with the acute-phase response, bone remodelling, atherothrombosis, anaemia of chronic disease and markers purported to reflect synovial lymphoid and myeloid cell infiltrates, as well as the potential of these biomarkers to differentially predict clinical and patient-reported outcomes with sarilumab vs. adalimumab.MethodsIn this post hoc analysis, serum samples were analysed at baseline and prespecified post-treatment timepoints up to week 24 in adults with moderate-to-severe active rheumatoid arthritis intolerant of or inadequate responders to methotrexate from the MONARCH trial (NCT02332590).ResultsGreater reductions in C-reactive protein (CRP; − 94.0% vs. –24.0%), serum amyloid A (SAA; − 83.2% vs. –17.4%), total receptor activator of nuclear factor-κB ligand (RANKL; − 18.3% vs. 10.5%) and lipoprotein (a) (− 41.0% vs. –2.8%) were observed at week 24 with sarilumab vs. adalimumab, respectively (adjusted p < 0.0001). Greater increases in procollagen type 1 N-terminal propeptide (P1NP) were observed with sarilumab vs. adalimumab at week 24 (22.8% vs. 6.2%, p = 0.027). Patients with high baseline SAA, CRP and matrix metalloproteinase-3 (MMP-3) were more likely to achieve clinical efficacy, including American College of Rheumatology 20% improvement criteria and Disease Activity Score (28 joints)-CRP < 3.2, and report improvements in patient-reported outcomes, including Health Assessment Questionnaire-Disability Index and pain visual analogue scale, with sarilumab than adalimumab.ConclusionSarilumab was associated with greater positive effects on bone remodelling and decreases in biomarkers of the acute-phase response, synovial inflammation and cardiovascular risk vs. adalimumab. High baseline concentrations of SAA, CRP and MMP-3 are predictive of clinical and patient-reported outcome responses to sarilumab treatment and prospective validation is warranted to confirm these results.Trial registrationClinicalTrials.gov, NCT02332590. Registered on 5 January 2015

MP49-09 CORRELATION BETWEEN IMMUNE-RELATED ADVERSE EVENTS SPECTRUM AND PROGNOSIS IN PATIENTS WITH ADVANCED UROTHELIAL CANCER TREATED WITH PEMBROLIZUMAB

You have accessJournal of UrologyBladder Cancer: Invasive I (MP49)1 Apr 2020MP49-09 CORRELATION BETWEEN IMMUNE-RELATED ADVERSE EVENTS SPECTRUM AND PROGNOSIS IN PATIENTS WITH ADVANCED UROTHELIAL CANCER TREATED WITH PEMBROLIZUMAB Takashi Tamiya*, Toshiki Kijima, Hajime Tanaka, Soichiro Yoshida, Junichiro Ishioka, Yoh Matsuoka, Noboru Numao, Yasuyuki Sakai, Kazutaka Saito, Nobuaki Matsubara, Takeshi Yuasa, Hithoshi Masuda, Junji Yonese, Yukio Kageyama, and Yasuhisa Fujii Takashi Tamiya*Takashi Tamiya* More articles by this author , Toshiki KijimaToshiki Kijima More articles by this author , Hajime TanakaHajime Tanaka More articles by this author , Soichiro YoshidaSoichiro Yoshida More articles by this author , Junichiro IshiokaJunichiro Ishioka More articles by this author , Yoh MatsuokaYoh Matsuoka More articles by this author , Noboru NumaoNoboru Numao More articles by this author , Yasuyuki SakaiYasuyuki Sakai More articles by this author , Kazutaka SaitoKazutaka Saito More articles by this author , Nobuaki MatsubaraNobuaki Matsubara More articles by this author , Takeshi YuasaTakeshi Yuasa More articles by this author , Hithoshi MasudaHithoshi Masuda More articles by this author , Junji YoneseJunji Yonese More articles by this author , Yukio KageyamaYukio Kageyama More articles by this author , and Yasuhisa FujiiYasuhisa Fujii More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000911.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Recent studies have suggested that immune-related adverse events (irAEs) caused by immune checkpoint inhibitors were associated with clinical benefit, and its predictive role could depend on the organs involved. This study aims to assess association between types of irAEs and pembrolizumab efficacy in patients with advanced urothelial cancer. METHODS: We retrospectively evaluated 97 patients with advanced urothelial cancer treated with pembrolizumab in second-line or later setting between January 2018 and March 2019. irAEs were categorized based on organs involved and graded per Common Terminology Criteria for Adverse Events version 4.0. Association between irAEs and pembrolizumab efficacy including objective response rate (ORR) and overall survival (OS) was assessed. RESULTS: In 97 patients (median age range, 70 [36-87] years; 76 men [78%], 21 women [22%]), 29 (30%) developed irAEs, 8 (8%) developed grade ≥3 irAEs, and 14 (14%) required systemic corticosteroid therapy. Most frequent irAEs involved endocrine (n=10) and skin (n=9). Twenty-six patients (27%) showed objective response; 15 of 29 patients with irAEs showed objective response (52%) in contrast with 11 of the 68 cases without irAEs (16%) (P < 0.01). ORR was higher in patients with endocrine (p=0.02), pneumological (p=0.06), or other irAEs (p=0.04); skin irAEs were not associated with ORR. Patients with irAEs showed significantly increased OS (median not reached vs 8.1 months, p=0.047). Endocrine irAEs (p=0.04) was associated with improved OS, while pneumological and skin irAEs were not. Development of ≥ Grade 3 irAEs, absence of visceral metastases, ECOG-performance status (0-1), and baseline CRP (<5.0 mg/L) were independent favourable predictors of OS. CONCLUSIONS: Endocrine irAE was associated with higher ORR and improved survival in patients with advanced urothelial cancer treated with pembrolizumab. Source of Funding: none © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e743-e744 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Takashi Tamiya* More articles by this author Toshiki Kijima More articles by this author Hajime Tanaka More articles by this author Soichiro Yoshida More articles by this author Junichiro Ishioka More articles by this author Yoh Matsuoka More articles by this author Noboru Numao More articles by this author Yasuyuki Sakai More articles by this author Kazutaka Saito More articles by this author Nobuaki Matsubara More articles by this author Takeshi Yuasa More articles by this author Hithoshi Masuda More articles by this author Junji Yonese More articles by this author Yukio Kageyama More articles by this author Yasuhisa Fujii More articles by this author Expand All Advertisement PDF downloadLoading ...

P276 Comparative effects of ixekizumab (IXE) vs adalimumab (ADA) across PsA patients defined by baseline characteristics: week 24 outcomes from SPIRIT-H2H

Abstract Background Comparisons of PsA treatment options to guide physicians are limited. When conventional treatment is insufficient, the recommendations is a biological agent, most frequently tumour necrosis factor (TNF)-inhibitors. IXE, an IL-17A antagonist biologic, showed superiority over TNF-inhibitor ADA for the simultaneous achievement of ACR50 and PASI100, and PASI100 alone in the SPIRIT-H2H trial at week 24. We analysed differences in efficacy outcomes between IXE and ADA by subgroups based on baseline clinical characteristics. Methods We conducted post-hoc analysis of data from SPIRIT-H2H (NCT03151551), a 52-week, multicentre, open-label, blinded assessor study patients with active PsA (defined as swollen joint count ≥3 and tender joint count ≥3), with a body surface area (BSA) ≥3% and insufficient response to ≥ 1 conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and naïve to biologic (b)-DMARDs. Patients were randomised 1:1 to IXE or ADA, while presence/absence of moderate-to-severe psoriasis (defined as PASI ≥12, static Physician Global Assessment ≥3 and BSA ≥10%) determined on-label dosing. Subgroups were defined by baseline enthesitis, dactylitis, fingernail psoriasis (presence/absence), BSA (&amp;lt;10%, ≥10%) and CRP (≤6 mg/L,&amp;gt;6 mg/L). A Fisher’s exact test was used for between group comparisons of efficacy outcome measures at 24 weeks (PASI90, ACR50/70, and minimal disease activity [MDA]). Missing data were overcome by non-responder imputation. Results At week 24, IXE and ADA demonstrated comparable efficacy in ACR50 response rates across all subgroups. ACR70 response in patients with fingernail psoriasis was significantly greater with IXE-treated vs ADA (p = 0.02) (table). PASI90 response with baseline enthesitis (p &amp;lt; 0.001), without dactylitis (p &amp;lt; 0.001), with fingernail psoriasis (p &amp;lt; 0.001), CRP (≤6 mg/L, p = 0.003; &amp;gt;6 mg/L, p = 0.036) and BSA (&amp;lt;10%, p = 0.010; ≥10%, p = 0.003) was significantly greater in IXE vs ADA (table). Significantly more IXE-treated patients vs ADA achieved MDA with baseline enthesitis (p = 0.002), without dactylitis (p = 0.015), with fingernail psoriasis (p &amp;lt; 0.001), CRP ≤6 mg/L (p = 0.046) and BSA ≥10% (p = 0.01) (table). A limitation is that this analysis was completed post-hoc, not controlled for multiplicity, and patients were not stratified by baseline disease characteristics. Conclusion IXE and ADA are associated with comparable efficacy and associated with a greater effect in certain subgroups. Results will aid clinicians when making treatment choices. Disclosures H. Tahir: Consultancies; Novartis, Eli-Lilly, Abbvie. A.J. Bradley: Shareholder/stock ownership; Eli Lilly. Other; Full time employee of Eli Lilly. M.H. Nassab: Other; Full time employee of Eli Lilly. B. Möller: None. J.S. Smolen: Consultancies; AbbVie, Amgen, Astra-Zeneca, Astro, BMS, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Medimmune, MSD, Novartis- Sandoz, Pfizer, Roche, Samsung, Sanofi-Aventis, UCB. Grants/research support; AbbVie, Eli Lilly, Novartis, Pfizer, Roche. C. Sapin: Shareholder/stock ownership; Eli Lilly. Other; Full time employee of Eli Lilly. C.F. Dionello: Consultancies; Novartis, Lilly, Janssen, Abbvie. Honoraria; Novartis, Lilly, Janssen, Abbvie, Roche, Pfizer. G. Meszaros: Shareholder/stock ownership; Eli Lilly. Other; Full time employee of Eli Lilly.

New onset of axial spondyloarthropathy in patients treated with isotretinoin for acne vulgaris: incidence, follow-up, and MRI findings

Oral isotretinoin is commonly prescribed for acne vulgaris. Several case reports and observational studies have reported serious musculoskeletal side effects; however, the incidence, imaging findings, and longitudinal follow-up data are limited for patients who develop inflammatory back pain (IBP). To assess the incidence of isotretinoin-triggered axial spondyloarthropathy (SpA) in acne vulgaris patients based on clinical features and MRI findings and to examine clinical and radiological outcomes following drug withdrawal. Five hundred thirteen acne patients receiving isotretinoin were screened for IBP; IBP patients were assessed for CRP, plain radiographs, and MRI of the sacroiliac joint. MRI-proven sacroiliitis was scored semi-quantitatively. Patients were followed longitudinally to assess SpA clinical course and longitudinal MRI sacroiliac joints, and CRP levels were reassessed 3weeks after patients were symptom-free, following isotretinoin discontinuation. Of the 513 patients, 23.98% developed IBP. MRI-proven sacroiliitis was detected in 42.3% of the symptomatic patients or 10.1% of the cohort. Among MRI-proven sacroiliitis cases, 51.9% fulfilled the Assessment of Spondyloarthritis International Society criteria for axial SpA. Mean CRP level was 32.05 ± 17.23mg/L at pain onset and 3.4 ± 2.7mg/L after symptom resolution. MRI findings completely resolved within 9months (mean 6.27 ± 1.7) after isotretinoin discontinuation. MRI scores positively correlated with baseline CRP levels and global acne grading system score, pain, and the Ankylosing Spondylitis Disease Activity Score. Isotretinoin-induced axial SpA is a prevalent side effect in acne vulgaris patients. Early detection and follow-up of isotretinoin-induced sacroiliitis can be facilitated by MRI. Cessation of isotretinoin resulted in complete resolution in all affected patients.Key Points• Detection of underdiagnosed isotretinoin side effects which are common but not always correctly diagnosed and managed.• Incidence, diagnosis, and management of these side effects in a real-world setting.• This is the first large prospective longitudinal cohort study to report on axial manifestations in patients treated with isotretinoin as well as the effect of drug cessation upon the clinical, laboratory, and radiological findings.

Factors associated with effectiveness of trifluridine/tipiracil versus regorafenib in patients with pretreated metastatic colorectal cancer (mCRC).

137 Background: Trifluridine/tipiracil (T) and regorafenib (R) are indicated for patients with refractory mCRC. Currently, no biomarkers are used to select which patient will benefit from which treatment. Methods: We retrospectively evaluated 212 patients who received T and/or R. Different factors associated with progression-free survival (PFS) and overall survival (OS) were analyzed. Results: T received 132, R 52, both drugs 28 patients. Median age was 64 (range 28-83), male 64%, PS 0 37%, median line of treatment 3, characteristic was similar between treatment groups. Median follow-up was 16.5 months. Median OS for T was 10.2, for R 6.9 months, P = 0.03. Factors significantly associated with OS were: ≥ 24 months from diagnosis of mCRC (0.49, P &lt; 0.001), PS 0 (HR 1.54, P = 0.007), baseline WBC &lt; 8 × 109/L (HR 0.47, P &lt; 0.001), normal baseline CRP (HR 0.47, P &lt; 0.001), ≥ 3 months from last therapy (fluoropyrimidine for T, anti-VEGF for R) (HR 0.66, P = 0.006). We developed a scoring system TASREG from these factors, 1 point for each factor, the overall score was the sum of these points and patients were divided into 3 groups: high risk group with 0 to 1 point, intermediate with 2 to 3, favorable with 4 or more points. OS for all patients according to risk group was 4.6 for high risk, 7.9 intermediate, 11.8 months favorable risk (P &lt; 0.001). Score was also significant for T and R group evaluated separately. Score was also significant for PFS. Factors associated with OS specific for T were neutropenia G≥2 (HR 0.34, P &lt; 0.001); for R normal baseline LDH (HR 0,40. P &lt; 0.001), no liver metastases (HR 0.45, P = 0.002), non-synchronous disease (HR 0,40, P &lt; 0.001). Conclusions: We could find factors associated with better outcomes for both treatment groups and factors specific for T or R. TASREG is simple prognostic tool for patients with refractory mCRC.

Glycyrrhizic acid as an adjunctive treatment for depression through anti-inflammation: A randomized placebo-controlled clinical trial

BackgroundRecently, abundant evidence indicated proinflammatory cytokines might play a crucial role in pathophysiology and treatment of depression. According to our preclinical research, we propose glycyrrhizic acid (GZA) for an adjunctive treatment owing to its safety, economical and anti-inflammatory profile. MethodsEligible participants were recruited and randomly allocated into independent treatment groups of SSRI+GZA (n = 30) and SSRI+PBO (placebo, n = 26). Depressive symptoms and specific serum biomarkers were detected during the 4-week treatment course. Afterward, the relationships between biomarkers and clinical effects were explored. ResultsDepressive symptoms relieved more in SSRI+GZA than SSRI+PBO, both at week 2 (P = 0.003) and week 4 (P = 0.016). Meanwhile, at week 4, both response rate (P = 0.035) and remission rate (P = 0.031) acutely became higher in SSRI+GZA compared with SSRI+PBO. Mediation analysis further demonstrated that TNF-α reduction mediated the association between GZA treatment and clinical improvement, the indirect effect lay between 0.124 and 3.514 (95% CI). The exploratory analysis also suggested that the symptomatic improvement existed in patients with high-inflammation (baseline CRP > 3 mg/L) rather than those with low-inflammation (baseline CRP ≤ 3 mg/L). LimitationsThe sample size in this study was not large enough and the follow-up duration was relatively short. ConclusionsThis study offers a novel strategy for the diagnosis, categorization, individualization and prognosis regarding upgrading traditional antidepressant therapy, which is from biomarkers to diagnostic indicator and therapeutic target. Patients are necessary to be classified according to the inflammatory state, those with high levels of baseline inflammation should receive combined treatment with anti-inflammatory agents like GZA.

DOP28 Understanding the molecular mechanisms of anti-TNF treatment failure in patients with Crohn’s disease: A pilot serum proteomic analysis of the PANTS cohort

Abstract Background Proteomic biomarkers have been linked to anti-TNF treatment failure, but previous studies have been insufficiently powered to stratify associations by drug level. The Personalised Anti-TNF Therapy in Crohn’s disease (PANTS) is a prospective UK-wide study investigating treatment failure in 1610 anti-TNF naïve patients. We aimed to identify proteomic markers of treatment failure. Methods We sampled patients with primary non-response (PNR) (n = 223) and remission (n = 219) who had a baseline CRP ≥4 mg/l and/or calprotectin &amp;gt;100 µg/g. PNR was defined at week 14 as ongoing steroids, or both of HBI failed to fall by ≥3 points or to ≤4 and CRP failed to fall by ≥50% or to ≤3 mg/l. Non-remission at week 54 was defined as HBI &amp;gt;4 and CRP &amp;gt;3 mg/l and no steroids. Targeted serum proteomic analysis of 180 proteins using Olink Inflammation and Immune Response panels were performed. Mann–Whitney U tests were used to identify baseline proteins that predicted PNR and non-remission. Sub-group analyses stratified by drug level were undertaken. Pharmacokinetic (PK) failure was defined as PNR with low drug level (infliximab level &amp;lt;2 mg/l, adalimumab level &amp;lt;6 mg/l) and pharmacodynamic (PD) failure as PNR despite adequate drug level. Significant proteins were entered into multivariable logistic regression models and Bayesian information criterion (BIC) with backward stepwise selection were used to build predictive models of treatment failure. We applied 10-fold cross-validation to test the models. P-values of &amp;lt; 0.05 were considered significant. Results Elevated fibroblast growth factor 21 (FGF21) (OR 1.3, CI 1.1–1.4, p = 3.4 × 10–5) and interleukin-10 receptor subunit α (IL10RA) (OR 1.6, CI 1.2–2.1, p = 6.3 × 10–4) predicted PNR (Figure 1). At week 14, FGF21 (OR 1.5, CI 1.3–1.9, p = 1.8 × 10–6) and IL10RA (OR 1.8, CI 1.3–2.3, p = 5.8 × 10–5) levels were also associated with PNR. Sub-group analyses showed baseline FGF21 (OR 1.4, CI 1.2–1.7, p = 2.0 × 10–4) predicted PK failure and that IL10-RA (OR 1.6, CI 1.1–2.2, p = 6.7 × 10–3) predicted PD failure (Figure 2). In separate models, non-remission at week 54 was predicted by baseline (FGF21; OR 1.3, CI 1.1–1.4, p = 1.4 × 10–4, IL10-RA; OR 1.5, CI 1.1–2.0, p = 3.6 × 10–3) and week 14 (FGF21; OR 1.4, CI 1.2–1.7, p = 3.6 × 10–4, IL10-RA; OR 1.7, CI 1.3–2.4, p = 1.7 × 10–4) FGF21 and IL10-RA levels. Model validation of baseline FGF21 and IL10-RA showed an area under the curve of 0.61 (CI 0.57–0.64) for PNR and 0.60 (CI 0.56–0.64) for non-remission at week 54. Conclusion Our study identified FGF-21 and IL10-RA as proteins of interest associated with PK and PD treatment failure, respectively. Functional studies to determine the molecular mechanism driving dysregulation of these proteins are required.

P507 Ustekinumab: Medium-term outcomes from a UK multicentre real-world cohort

Abstract Background Ustekinumab is effective at inducing and maintaining remission of Crohn’s disease (CD) in clinical trials. However real-world practice may vary regarding use of concomitant immunomodulator (IM), dosing schedule and patient selection. We present the largest UK real-world, multi-centre study of effectiveness. Methods The cohort comprised adult patients initiated on ustekinumab for CD from October 2016–18 at 3 tertiary London centres. Clinical endpoints were (i) remission (Harvey Bradshaw Index (HBI) ≤4) (ii) response, (reduction in HBI of ≥3 or sustained HBI≤4 points) at 3, 6 and 12 months. Biological endpoints were remission and response (CRP &amp;lt;5mg/l in patients with a baseline CRP&amp;gt;5mg/l, and 50% reduction in CRP, respectively). Results 211 patients were included (Table 1), of whom 207 (98%) were biologic exposed and 59 (28%) had failed 3 biologics. All patients received i.v. induction and 203 (96%) received a s.c. dose at week 8. At 6 and 12 months, 133 (74.8%) and 109 (73.6%) patients, respectively, were on 8 weekly dosing. Dosing schedule did not impact clinical and biological outcome at 6 and 12 months. Discontinuation occurred in 4 (1.9%), 20 (9.5%) and 50 (23.7%) patients by 3, 6 and 12 months respectively. Reasons for stopping included: drug reactions (4(1.9%)), partial response (4 (1.9%)), loss of response (10 (4.7%)) and primary non-response. (24 (11.4%)). Clinical and biological outcomes at 3, 6 and 12 months are shown in Figure 1. Adverse events occurred in 27 (12.8%) patients. IM were prescribed in 49 (23%) at baseline and continued in 46 (21.8%), 36 (17.1%), 27 (12.8%) at 3, 6 and12 months respectively. There was no significant difference in median persistence (months) on ustekinumab between patients who were on an IM at baseline vs. those not (15.2 (95% CI 0–32.2) vs. 23.3 (17.3–29.4) months, p = 0.4). Likewise, there was no significant difference in clinical or biological outcome between patients with colonic vs. ileocolonic or ileal disease. Finally, there was no significant difference in median persistence on ustekinumab between patients with and without a history of perianal disease (19.5 (95% CI 9.2–29.8) vs. 22.9 (18.6–27.2) months, p = 0.8). Conclusion Ustekinumab is effective in a real-world cohort. In keeping with trial data, we did not find evidence of improved outcomes with the use of a concomitant IM, nor differential outcomes when considering perianal and isolated colonic disease.

P721 Early vedolizumab trough levels are associated with induction therapy outcome

Abstract Background Vedolizumab (VDZ) is a monoclonal antibody which targets a4b7 integrin. It has been demonstrated to have efficacy in the induction and maintenance of remission in patients with both ulcerative colitis (UC) and Crohn’s disease (CD). We aimed to determine factors, including drug levels, associated with success of VDZ induction therapy. Methods Patients were recruited prospectively from three Irish Academic Medical Centres. Individuals were included if &amp;gt;18 years, with an established diagnosis of UC or CD and due to commence VDZ therapy. Disease activity scores were assessed on day of infusion (week 0) and again at week 14. All patients received standard per protocol VDZ induction therapy for UC and CD. Serum samples for trough VDZ level assessment were collected prior to week 2 and 6 VDZ infusions. The primary endpoint was steroid-free remission following VDZ induction assessed at week 14. Steroid free remission was defined as the absence of corticosteroid use and a partial mayo score ≤ 1 (for UC patients) or HBI &amp;lt; 5 (for CD patients). All continuous data are presented as median (range). p-value of &amp;lt;0.05 was considered significant in all analyses. Results Forty-four patients were recruited of whom n = 40 had available follow-up to week 14 [median age at study entry was 51.95 (18.2–75.8); 55% of cohort had CD]. Concomitant immunomodulator use and corticosteroid use at VDZ initiation was 22% and 20% respectively. 70% had prior biologic exposure. Baseline partial Mayo score at study entry was 4 (2––6) while baseline HBI was 7 (1––20). Baseline CRP was 3.6 mg / L (1––43), albumin 41 g / L (30––52) and faecal calprotectin 764 (16.4––1250). Week 2 and week 6 trough VDZ concentrations were 25.1 μg/ml (0––56) and 20.2 μg/ml (0––66), respectively. Eighteen patients (45%) were in steroid free remission after induction at week 14. There was an association between increased week 6 trough VDZ levels and steroid free remission at week 14, p = 0.015. There was no association between week 2 trough VDZ levels and therapy outcome. Receiver operating characteristics curve was plotted for Week 6 VDZ levels with the area under the curve (95% confidence interval) being 0.742 (0.572––0.912). A cut off VDZ level of &amp;lt;16.7 µg/ml gave a sensitivity of 80% and specificity of 63%. An elevated baseline CRP (&amp;gt;5mg/L) was significantly associated with and absence of steroid free remission at week 14, p = 0.001. Conclusion Early vedolizumab trough levels are associated with steroid free remission following induction therapy. Vedolizumab therapeutic monitoring may have value in a clinical setting, however, further prospective studies and clinical validation is required.

P577 Ustekinumab in actual clinical practice: our centre experience

Abstract Background Crohn’s disease is an entity with wide variability in its clinical manifestations, which mainly affects the gastrointestinal tract, and may also involve another organs. We have a wide variety of treatments available, being the most recent ones biological therapies. One of them is ustekinumab, which due to its innovative mechanism of action has improved the quality of life of many patients with an excellent safety profile. Our objective was to analyze the baseline situation of 37 patients undergoing treatment with ustekinumab in our centre and the evolution of different clinical and analytical parameters at 12, 24 and 52 weeks after starting it. Methods 37 patients currently receiving ustekinumab treatment with indication of Crohn’s disease at Virgen de las Nieves Hospital were selected (Tables 1 and 2). Clinical response was analyzed according to the Harvey–Bradshaw Index (HBI) (clinical remission &amp;lt;4, clinical response decrease ≥3 points above the baseline), blood and stool test (CRP and calprotectin) at weeks 12, 24 and 52, need for surgery and safety profile (Table 3). Results There are no significant differences in HBI or baseline CRP depending on previous or not treatment with anti-TNF or vedolizumab. No differences in HBI, CRP at weeks 12, 24 and 52 depending on if previous treatment with anti-TNF or vedolizumab. The decrease in the median values of HBI was statistically significant at weeks 12, 24 and 52; as well as CRP values at weeks 24 and 52 (Table 3). According to HBI, clinical response was obtained in 41,38%, 50% and 61,11% of patients at weeks 12, 24 and 52 and clinical remission in 20,69%, 33,33% and 27,78% respectively (Table 3). No response predictors were identified at week 12 except for non-perianal fistulas associated with a greater response (58,3% vs. 41,7%; p = 0,0459) (Table 4). Conclusion In this group of patients potentially difficult to treat (62% previous surgery, long-term disease, 95% previous treatment with immunomodulators and/or biological therapies (66% ≥2 anti-TNF), etc.), ustekinumab achieves clinical response in 41,38%, 50%, 61,11% at week 12, 24 and 52. Surgery was required in 2 cases and only 3 patients suffered relevant adverse effects. In a pivotal study of ustekinumab UNITI-1, 50,6% of patients who received the induction dose of 6 mg/kg had previously been treated with ≥2 anti-TNF, in our group, 65,71%. In our cohort, only 29,73% of patients received corticosteroids concomitantly at the start of ustekinumab treatment vs. 43,3% at UNITI-1. Despite these differences against our group, clinical response and remission data are similar to UNITI-1 (41,38% vs. 37,8% and 20,69% vs. 20,9% respectively). Prospective studies with more patients could identify who would benefit most from this treatment.

P617 Mesenchymal stromal cells of bone marrow reduce the risk of postoperative recurrence of Crohn’s disease

Abstract Background Crohn’s disease (CD) in the form of terminal ileitis occurs in approximately 1/3 of CD patients and is often complicated by the formation of ileum stricture or ileocecal valve. The operation of choice is resection of ileocecal Department with the formation of ileo of ascendants. Depending on the combination of risk factors, as well as on the effectiveness of previous anti-relapse therapy, patients after surgery should be stratified into groups with different risks of postoperative recurrence. The objective of the study was to evaluate the effectiveness of mesenchymal stem/stromal cells (MS/SC) as anti-relapse therapy in patients with low-risk CD after ileocecal resection. Methods Thirty-six patients with CD in the form of terminal ileitis with a stricture of the terminal ileum with signs of intestinal obstruction after the ineffectiveness of the course of conservative therapy (application of GCS) underwent resection of the ileocecal Department with the formation of ileo-ascendoanastomosis. All patients had a low risk of postoperative recurrence of Crohn’s disease. However, the first group of patients aged 19 to 58 years (Me-29) (n = 18) received MS/SC. The second group of patients aged 20 to 68 years (Me-36) (n = 18) received mesalazine 4 gr/day. The follow-up period was 60 months. The monitoring was carried out by endoscopic picture and/or CT-enterography, C-RP level, faecal calprotectin (FCP). Average baseline CRP in the first group was 29.5 ± 3.2 mg/l, in the second – to 27.75 ± 3.0 (p = 0.73), the level of the FCP in the first group 1019.4 ± 97.2 mkg/g, in the second – 998.8±127.3 mkg/g (p = 0,9). Results After 24 months in the first group of patients the average level of C-RP was 9.5 ± 1.9 mg/l, in the second group 17.8 ± 3.3 mg/l (p = 0.027). The level of the FCP in the first group 98.0 ± 12.1 mkg/g, in the second 121.7 ± 14.2 mkg/g (p = 0.27). After 24 months of follow-up, 1 (5.5%) patient from the first group (n = 18) had a relapse that required the appointment of GCS. In the second group, relapse occurred in 4 (22.2%) patients out of 18 (RR 0.25; 95% CI 0.031–2.025; p = 0.15). After 60 months in the first group of patients, the average level of C-RP was 10.76 ± 2.1 mg/l, in the second group 19.2 ± 3.5 mg/l (p = 0.039). The level of the FCP in the first group of 100.4 ± 13.7 per mkg/g, in the second 191.7 ± 24.9 mkg /g (p = 0.002). After 60 months of follow-up, 1 (5.5%) patients from the first group had a relapse. In the second group, relapse occurred in 8 (22.2%) patients out of 18 (RR 0.125; 95% CI 0.017–0.9; p = 0.008). Conclusion The use of mesenchymal stem/stromal cells (MS/SC) as anti-relapse therapy in patients with low-risk CD after ileocecal resection significantly reduces the risk of postoperative recurrence of CD.

Acute Phase Proteins as Predictors of Survival in Patients With Acute Exacerbation of Chronic Obstructive Pulmonary Disease Requiring Mechanical Ventilation

Few studies have tried to assess prognostic variables in chronic obstructive pulmonary disease (COPD) patients requiring mechanical ventilation (MV). We evaluated serum C reactive protein, (CRP) pre-albumin (PA) and transferrin (TR) levels in AE-COPD patients requiring MV as prognostic markers of in hospital mortality. 93 AE-COPD patients on MV were evaluated. Detailed clinical evaluation was done daily. Serum CRP & PA were measured on admission, 3rd, 8th and 16th day; TR was measured on admission, 8th and 16th day. Demographics, baseline parameters, CRP, PA and TR were correlated with mortality. Of 93 patients, 49 (52.69%) survived whereas 44 patients (47.31%) died. APACHE II, serum urea & albumin were similar in survivors & non-survivors. Baseline CRP (≥10.5 mg/dl) had sensitivity of 60.5%, specificity of 60.2%, with area under curve (AUC) of 0.62 as predictor of mortality. CRP (≥7 mg/dl) on day 3 had sensitivity (65.5%) and specificity (63.3%) with AUC 0.70 as predictor of mortality. Baseline serum prealbumin was 11.00 (0.09–29.26) mg/dl, and similar in survivors & non-survivors (p = 0.7). Prealbumin at day 8 (n = 50) < 13.5 mg/dl had sensitivity 54.6%, and specificity 51.4% with AUC 0.54 (95% CI 0.34–0.75) as predictor of mortality. Transferrin at day 8 (n = 50) of <148.9 had sensitivity 63.4% and specificity 61.4% with AUC 0.61 with respect to mortality. High CRP levels at baseline, persistently elevated CRP (on day 3) may predict mortality in AE-COPD patients requiring MV. Further studies are required to establish prognostic variables in this patient population.

1716. Baseline Serum C-Reactive Protein Level Predicts Mortality in Cryptococcal Meningitis

BackgroundC-reactive protein (CRP) is an acute-phase protein produced by the liver in response to systemic inflammation. CRP is a helpful surrogate biomarker widely used in various infections, particularly for following the progression and resolution of infection. We aimed to determine the association between baseline CRP level and cryptococcal meningitis outcome.MethodsWe reviewed 168 prospectively enrolled HIV-infected Ugandans with confirmed first-episode cryptococcal meningitis. Baseline serum samples collected within 5 days from diagnosis had CRP levels measured and categorized into quartiles. We compared baseline serum CRP with 18-week survival using unadjusted time-to-event analysis.ResultsOf 168 participants, the first quartile of baseline serum CRP was 83.6 mg/L. Baseline CD4 count, HIV viral load, and cerebrospinal fluid results did not differ by quartile. Participants with CRP > 49.5 mg/L more likely presented with Glasgow Coma Scale <15 (P = 0.03). The 18-week mortality rate was 54.8% (46/84) in the highest two quartile CRP groups (49.5 mg/L), 40.5% (17/42) in the mid-range CRP group (29–49.5 mg/L), and 14.3% (6/42) in the low CRP group (<29 mg/L) (P < 0.001) (Figure 1).ConclusionHigher baseline serum CRP is associated with increased mortality in HIV-infected individuals with first-episode cryptococcal meningitis. The serum CRP could be a surrogate marker for undiagnosed co-infections or may reflect immune dysregulation leading to worse outcomes in persons with advanced AIDS and concomitant cryptococcal meningitis. Additional studies investigating more specific inflammatory biomarkers and the longitudinal trend in CRP with effective therapy would be informative. Disclosures All authors: No reported disclosures.

Prediction of toxicity in R/R DLBCL treated with Axicabtagene Clioleucel (19-28z CAR T)

Abstract Background A cytokine release syndrome (CRS) or neurotoxicity described as a chimeric antigen receptor (CAR) T Related Encephalopathy Syndrome (CRES) is one of the main complications while CD19 CAR T has been successful in relapsed/refractory (R/R) B cell malignancies. CRS and/or CRES have been associated with standard biomarkers such as CRP and ferritin but also with cytokines. We report the results of cytokine analysis using a point of care (POC) device to predict immune-related toxicities in patients with R/R DLBCL treated with axicabtagene ciloleucel (axi-cel). Methods Patients treated with commercial axi-cel in Moffitt Cancer Center were included in this study. Serum samples were collected prior to lymphodepleting chemotherapy at baseline and then during hospitalization. Based on 38 serum cytokineś analysis in B-cell acute lymphoblastic leukemia patients treated with 19-28z CAR T and results of published studies, 8 serum proteins were selected to monitor. CRS and CRES were prospectively graded by Lee criteria and CARTOX respectively. Results 41 patients were identified. Median age was 64 years old (76% male). Non-severe (grade 0-2) and severe (grade 3-5) CRS were observed in 93% and 7% respectively while non-severe and severe CRES were observed in 71% and 29% respectively. 2 patients died in the setting of severe toxicity. Baseline CRP, ferritin, IL-6 levels were significantly elevated in the patients who developed severe CRS and/or CRES. Baseline angiopoietin-2/angipoietin-1 ratio (ANG-2/1) was also correlated with severe CRES. In select cases, monitoring of cytokines provided clinical insight that wasnt evident from standard biomarkers. Conclusions We observed correlations between severe toxicities and elevated serum cytokine levels of baseline IL-6 and ANG-2/1 suggesting that these biomarkers may be utilized to predict severe toxicity in patients treated with CAR T. Monitoring of cytokines using a POC device is feasible and would be useful clinically.

EP1.16-37 Correlation of Serum Albumin and CRP Levels with Chemotherapy Toxicity in Patients of Metastatic Lung Cancer

significant proportion of patients of lung cancer present with metastatic disease. Chemotherapy is often offered as first line treatment if patients does not have driver mutations in a specific targetable oncologic pathway and is fit to receive systemic therapy. Systemic inflammation associated with advanced cancer is often regarded as one of the factors for poor prognosis in lung cancer patients. High level of CRP and low levels of albumin are regarded as markers of systemic inflammation and prior studies have shown poor survival in such patients. It has also been shown that systemic inflammation alters the metabolism of chemotherapeutic agents resulting in either treatment failure or increased toxicity, both of which can lead to poor outcomes. This study aims to identify if increased systemic inflammatory response leads to enhanced toxicity with chemotherapeutic agents used in palliative setting in patients of metastatic lung cancer, and in turn poorer survival. Trial design Objectives Primary objective – Correlating chemotherapy toxicity with patients’ baseline albumin and CRP levels Secondary objective - Correlating CRP and Albumin levels with PFS and OS Materials and Methods Study Design - Patients with a tissue diagnosis of lung cancer will be prospectively enrolled in the study after informed consent. All clinically relevant details will be entered in a clinical proforma. Site and duration of study - Kidwai Cancer Institute; June 2018 to Dec 2019 Sample size – All patients meeting the inclusion criteria between the study time period will be included Inclusion Criteria Patients of Metastatic Biopsy Proven Lung Cancer Age 18 – 80 Planned for chemotherapy with a platin Doublet Albumin > 2.0 Exclusion Criteria Presence of targettable driver mutations Any other Synchronous / Metachronous cancer Any other uncontrolled medical comorbidities Statistical Analysis The Mann-Whitney U test and the χ2 test will be used to determine statistically significant differences 1/10/2019 #337: Correlation of Serum Albumin and CRP Levels with Chemotherapy Toxicity in Patients of Metastatic. https://cpaper.ctimeetingtech.com/elcc2019/submission/preview/print?publication_id=337 2/2 Kaplan-Meier method will be used to assess survival curves; Log-rank test to evaluate the statistical significance of differences and Cox proportional hazards model for multivariate analysis of the effect of clinicopathological factors on survival. This study aims to identify if increased systemic inflammatory response leads to enhanced toxicity with chemotherapeutic agents used in palliative setting in patients of metastatic lung cancer, and in turn poorer survival.

Abstract CT001: Biomarkers of systemic inflammation associated to reduced clinical activity of atezolizumab monotherapy in patients with metastatic triple negative breast cancer

Abstract Background: Immune checkpoint blockade by anti-PD-L1 antibody atezolizumab has demonstrated clinical benefits in metastatic triple negative breast cancer (mTNBC). IL-6 and IL-8 myeloid inflammation is linked to poor prognosis in cancer patients treated with chemotherapy, but its association with single agent atezolizumab-treated patients with mTNBC remains unknown. In this study, we investigated the association of biomarkers (BM) of systemic inflammation with clinical outcomes in patients with mTNBC treated with atezolizumab monotherapy. Methods: Baseline pre-treatment plasma samples were collected from mTNBC patients enrolled in the Phase I atezolizumab monotherapy clinical trial PCD4989g (NCT01375842, n = 116). IL-6, IL-8 and CRP were tested by ELISA or Luminex assays and their levels were assessed for association with baseline clinical demographic characteristics and atezolizumab clinical activity for response rate (ORR), progression free (PFS) and overall survival (OS). Results: Baseline IL-6, IL-8, and CRP levels were positively associated with the clinical prognostic traits ECOG performance status (&amp;gt;0), presence of liver metastases, large size of target lesions (&amp;gt;=6.5cm), and increased LDH (&amp;gt;=1.5xULN). Elevated baseline IL-6 and CRP, but not IL-8, were also linked with later lines of therapy (&amp;gt;=2). Univariate analyses showed that IL-6 (&amp;gt;=15pg/ml), IL-8 (&amp;gt;=11.4pg/ml) and CRP (&amp;gt;=3mg/L) were associated with reduced OS and PFS (Table), but only CRP was associated to reduced ORR. Multivariate analyses considering the aforementioned clinical demographic variables showed that IL-6 (HR 2.00 [1.16-3.38]); and CRP (HR 2.74 [1.49-5.28]), but not IL-8 (HR 1.07 [0.78-1.74]), were associated with OS. Conclusion: The systemic IL-6/CRP inflammatory axis is an independent factor linked with poor outcomes of mTNBC patients treated with atezolizumab monotherapy and may play unique roles in affecting the anti-tumor activity in this hard to treat patient population. Table (univariate)BMLow mPFSBMHigh mPFSPFS HR (CI 95%)BMLow mOSBMHigh mOSOS HR (CI 95%)IL-6 (&amp;gt;=15pg/ml)1.45 mo1.35 mo1.87 (1.23-2.83)12.6 mo2.6 mo2.55 (1.63-4.01)IL-8 (&amp;gt;=11.4pg/ml)1.94mo1.34 mo2.00 (1.36-2.95)12.6 mo6.42 mo2.05 (1.34-3.14)CRP (&amp;gt;=3mg/L)2.50 mo1.35 mo2.07 (1.31-3.25)20.5 mo6.9 mo3.33 (1.91-5.79) Citation Format: Yijin Li, Marcella Fassò, Leisha A. Emens, Luciana Molinero. Biomarkers of systemic inflammation associated to reduced clinical activity of atezolizumab monotherapy in patients with metastatic triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT001.

Prediction of trifluridine/tipiracil (TAS-102) effectiveness in patients with refractory metastatic colorectal cancer (mCRC): Real-life data from the Czech Republic.

e15102 Background: TAS-102 is effective in refractory mCRC and significantly improved survival versus placebo. Currently no predictive biomarkers are established and used in clinical practice. Methods: We analyzed data of 160 patients treated with TAS-102 in real clinical practice in Czech Republic. Different factors associated with progression-free survival (PFS) and overall survival (OS) were evaluated. Results: Baseline patients’ characteristics: median age 66 years (range 28-83), 106 patients were male (66.3 %), ECOG PS 0 had 38.1 %, RAS wt 45 %. Anti-VEGF treatment had 83.1 %, anti-EGFR 43.8 %. Median number of TAS-102 treatment line was 3 (range, 2 – 8), median TAS-102 cycles 3 (range 1 – 27). At the time of analysis 15 % continued in treatment, 73.7 % discontinued due to progression, 6.9 % due to toxicity, 3.8 % decided to discontinue in treatment. Median PFS was 3.3 months (95% CI, 3.0 – 3.5), and median OS 10.2 months (95% CI, 8.9 – 11.8). Factors significantly associated with PFS and/or OS were: PS, time from diagnosis of mCRC, initiation of TAS-102 treatment &gt; 3 months from last fluoropyrimidine, baseline CRP, WBC, neutrophils count, monocytes count, NLR, neutropenia ≥ G2, diarrhea ≥ G1, thrombocytopenia ≥ G2, required TAS-102 dose reduction and cycle delay. We developed a scoring system TAScore from factors at the beginning of treatment (PS 0, initiation of TAS-102 &gt; 3 months from fluoropyrimidine, time from diagnosis of mCRC, baseline CRP, WBC, monocytes count &lt; 0.5 × 109/L). For each factor patient received 1 point, the overall score was the sum of these points and patients were divided into 3 groups: high risk group with 0 to 1 point, intermediate with 2 to 3, favorable with 4 or more points. OS according to risk group was: 5.7 months for high risk (11 patients), 8.7 for intermediate (63), 12.8 for favorable (59) (P &lt; 0.0001). TAScore was also associated with PFS: 2.4 months for high risk, 2.9 intermediate and 3.9 for favorable risk group (P &lt; 0.0001). Conclusions: TAS-102 is effective in patients with refractory mCRC. We propose simple scoring system TAScore to help with precise patient selection at the beginning of TAS-102 treatment.