Abstract 404: Prognostic value of soluble and cell surface immune-checkpoint molecules in advanced non-small cell lung cancer (NSCLC) patients receiving anti-PD-1/-L1 immunotherapy

2019 ◽  
Author(s):  
Imad Tarhoni ◽  
Mary Jo Fidler ◽  
Ibtihaj Fughhi ◽  
Connor Wakefield ◽  
Revathi Kollipara ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Surface ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Prognostic Value ◽  
Small Cell ◽  
Small Cell Lung ◽  
Immune Checkpoint Molecules ◽  
Nsclc Patients

scholarly journals Subunits of ARID1 serve as novel biomarkers for the sensitivity to immune checkpoint inhibitors and prognosis of advanced non-small cell lung cancer.

2020 ◽  
Author(s):  
Dantong Sun ◽  
Lu Tian ◽  
Yan Zhu ◽  
Yang Wo ◽  
Qiaoling Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Novel Biomarkers ◽  
Nsclc Patients

Abstract Introduction Patients with advanced non-small cell lung cancer (NSCLC) benefit from treatment with immune checkpoint inhibitors (ICIs). Biomarkers such as programmed death-ligand 1 (PD-L1), the tumor mutational burden (TMB) and the mismatch repair (MMR) status are used to predict the prognosis of ICIs therapy. Nevertheless, novel biomarkers need to be further investigated, and a systematic prognostic model is needed for the evaluation of the survival risks of ICIs treatment.Methods A cohort of 240 patients who received ICIs from the cBioPortal for Cancer Genomics was evaluated in this research. Clinical information and targeted sequencing data were acquired for analyses. The Kaplan-Meier plot method was used to perform survival analyses, and selected variables were then confirmed by a novel nomogram constructed by the “rms” package of R software.Results Seven percent of the NSCLC patients harbored ARID1A mutations, while 4% of the NSCLC patients harbored ARID1B mutations. Mutations in ARID1A and ARID1B were confirmed to be associated with sensitivity to ICIs. Patients harboring these mutations were found to have a better response to treatment (ARID1A: P=0.045; ARID1B: P=0.034) and prolonged progression-free survival (ARID1B: P=0.032). Here, a novel nomogram was constructed to predict the prognosis of ICIs treatment. Elevation of the TMB, enhanced expression of PD-L1 and activation of the antigen presentation process and cellular immunity were found to be correlated with ARID1A and ARID1B mutations.Conclusion ARID1A and ARID1B could serve as novel biomarkers for the prognosis and sensitivity to ICIs of advanced NSCLC.

scholarly journals P2-095: Prognostic value of the determination of K-ras mutations plasma in advanced non-small cell lung cancer (NSCLC) patients

2007 ◽  
Vol 2 (8) ◽  
pp. S528-S529
Author(s):  
Rafael Sirera ◽  
Carlos Camps ◽  
José-Luis González-Larriba ◽  
Juan Lao ◽  
R García-Gómez ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Prognostic Value ◽  
Small Cell ◽  
Small Cell Lung ◽  
Ras Mutations ◽  
Nsclc Patients

Circulating biomarkers and outcomes in advanced non-small cell lung cancer patients treated with anti-PD1 (program death 1 receptor) monoclonal antibodies.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20592-e20592
Author(s):  
Mary J. Fidler ◽  
Marta Batus ◽  
Imad Tarhoni ◽  
Selina Sayidine ◽  
Cristina L. Fhied ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune System ◽  
T Cell ◽  
Pilot Study ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Prognostic Value ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

e20592 Background: Current evaluation of immunohistochemical expression of PDL-1 (program death receptor 1 ligand) can select some non-small cell lung cancer (NSCLC) patients who may benefit from anti-PD1 directed therapy. It is an imperfect marker and there is little information about systemic modulation of the immune system on therapy. In this study we explored the prognostic value of baseline circulating immune checkpoint and inflammatory molecules in advanced non-small cell lung cancer (NSCLC) patients receiving anti-PD1 therapy. Methods: Prospectively collected serum from advanced NSCLC patients receiving nivolumab or pembrolizumab were evaluated with the MILLIPLEX Human High Sensitivity T-cell (17-plex) and ProcartaPlex Human Immuno-Oncology Checkpoint (14-plex) panels on our Luminex FlexMAP 3D. Biomarker level cutoffs were optimized and evaluated against progression-free survival (PFS) and overall survival (OS) using log-rank analysis. Results: 21 cases were enrolled in this pilot study: 72% Caucasian, 61% female, 24% never-smokers. IL-10 was found to have a significant association with both PFS (p = 0.0055) and OS (p = 0.024), with levels below 3.32 pg/mL being associated with a superior clinical outcome. We also found IL-2 and IL-6 to have significant associations with PFS (p = 0.033 and 0.040, respectively), again, with low levels being associated with a superior outcome. Neither of these had significant associations with OS. Low circulating levels of the T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) protein were associated with superior PFS (p = 0.036), and a weak trend (p = 0.19) for OS. Conclusions: In this small exploratory pilot study we identified several circulating molecules associated with inflammation and immune system regulation that may have prognostic value for anti-PD-1 therapy. Notably, TIM-3 is a Th1-specific protein associated with macrophage activation and is also a component of T-cell exhaustion along with LAG3 and PD-1. Additional studies to follow up on these findings in larger cohorts are underway.

Plasma-derived cfDNA to reveal potential biomarkers of response prediction and monitoring in non-small cell lung cancer (NSCLC) patients on immunotherapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9588-9588
Author(s):  
Francesco Vallania ◽  
Karen Assayag ◽  
Peter Ulz ◽  
Adam Drake ◽  
Hayley Warsinske ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Transcription Factor ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Response Prediction ◽  
Small Cell ◽  
Cellular Composition ◽  
Small Cell Lung ◽  
Nsclc Patients

9588 Background: Immune checkpoint inhibitors have shown promising results in many advanced cancers, but the response rate remains low. Various molecular and cellular biomarkers, such as elevated tumor-infiltrating cytotoxic T cells and Natural Killer (NK) cells at baseline, are associated with response. Blood-based biomarkers to predict or monitor response remain challenging to develop. Here we investigate the potential of cell-free DNA (cfDNA) biomarkers to predict response to the PD-1 immune checkpoint inhibitor nivolumab in patients with refractory metastatic non-small cell lung cancer (NSCLC). Methods: Plasma from stage IV NSCLC patients enrolled in ALCINA (NCT02866149) was collected before (baseline, BL, n = 30) and at week 8 (W8, n = 17) of nivolumab therapy. Response was determined using RECIST 1.1 (responders n = 5; non-responders n = 25). Whole-genome sequencing was performed to characterize cfDNA fragments. Tumor fraction (TF) was assessed using ichorCNA. Cellular composition was estimated by deconvolution of cfDNA co-fragmentation patterns, and transcription factor activity was estimated by measuring binding site accessibility across the genome. Results: Although estimated TF at baseline did not predict response to nivolumab, NK cell levels estimated by cell-mixture deconvolution were significantly higher in responders at BL (p < 0.05). Furthermore, estimated monocyte levels at W8 strongly correlated with overall survival (r = 0.75, p < 0.0005, HR = 15.02) and were significantly higher in responders (p < 0.05). By evaluating changes in transcription factor binding activity, we identified factors with greater accessibility in non-responders at baseline (DEAF1, THAP11) and W8 (DUX4, PDX-1). Conclusions: Plasma cfDNA signatures may be useful for response prediction and monitoring in NSCLC patients on immunotherapy. Our results suggest that changes in the immune system, as reflected by cellular composition and transcriptional activity inferred from cfDNA, may provide biological insights beyond TF alone that may benefit biomarker discovery and drug target identification.

Impact of SWI/SNF complex mutations in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors: Immuno-oncology biomarker study in LC-SCRUM-Japan (LC-SCRUM-IBIS).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9530-9530
Author(s):  
Kiyotaka Yoh ◽  
Shingo Matsumoto ◽  
Naoki Furuya ◽  
Kazumi Nishino ◽  
Shingo Miyamoto ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Clinical Outcomes ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

9530 Background: The SWI/SNF chromatin remodeling complex is reported to be involved in sensitivity and resistance to immune checkpoint inhibitor (ICI). However, their role in non-small cell lung cancer (NSCLC) remains unclear. We examined the relationship between SWI/SNF complex mutations and clinical outcomes of ICI in patients with NSCLC. Methods: Of 1017 lung cancer patients enrolled in LC-SCRUM-IBIS, 350 patients were analyzable for whole-exome sequencing (WES). WES data were used to analyze the presence of mutations in 29 major subunits of the SWI/SNF complexes. ARID1A and SMARCA4 mutations were also evaluated in a targeted NGS panel (Oncomine comprehensive assay, OCA). PD-L1 expression by 22C3, tissue tumor mutational burden (tTMB) by WES, STK11 and KEAP1 mutations by WES or OCA were also assessed. Durable clinical benefit (DCB) including CR, PR and SD > 6 mos to ICI, progression-free survival (PFS) and overall survival (OS) were compared in status of each of SWI/SNF complex mutations and other factors. Results: At least one mutation in any subunits of the SWI/SNF complex was present in 28% of NSCLC patients. The most common mutated subcomplexes were SMARCA4 (12%), BAF (7%: ARID1A, 4%), non-canonical BAF (3%), PBAF (3%), and SMARCA2 (2%). Of 101 NSCLC patients treated with PD-1/PD-L1 inhibitors, SMARCA4 mutations tended to be associated with lower DCB (16 vs 31%) and shorter median PFS (1.9 vs 3.6 m) and OS (7.4 vs 18.1m). Patients with ARID1A mutations tended to have better clinical outcomes (DCB, 40 vs 28%) compared to those without mutations. No significant associations were found between PD-L1 expression and SMARCA4 or ARID1A mutations. Patients with STK11/KEAP1 mutations had lower rate of PD-L1 expression (TPS > 50%) (18% vs 48%, P = 0.03) and worse clinical outcomes (DCB, 6 vs 33%) compared to those without mutations. There was no significant association between a tTMB status and clinical outcome. Conclusions: SMARCA4 and ARID1A mutations appear to affect clinical outcomes of ICI in NSCLC patients. These findings indicate that SWI/SNF complex mutations may serve as a predictive biomarker for ICI in NSCLC patients.

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