Human leukocyte antigen expression in paired primary lung lesions and brain metastases in non-small cell lung cancer.

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 43-43
Author(s):  
Jarrett Failing ◽  
Marie-Christine Aubry ◽  
Aaron Scott Mansfield
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Human Leukocyte ◽  
Small Cell ◽  
Small Cell Lung ◽  
Primary Tumors ◽  
Primary Nsclc

43 Background: Human leukocyte antigens (HLA) are crucial for cytotoxic T cell responses to cancer. Loss of HLA expression is a mechanism of tumor immune escape and may contribute to resistance to immunotherapy. In patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors we have observed discordant responses between brain metastases and extracranial disease and reported on differential PD-L1 expression and clonal T cell infiltration between paired primary lung lesions and brain metastases. In this project we sought to evaluate whether HLA expression was retained in metastatic NSCLC. Methods: Adult patients with paired primary NSCLC and brain metastases were identified from our institution’s tissue registry. HLA-A cell membrane expression on tumor cells was determined by immunohistochemistry with an anti-HLA-A antibody. Tumors with greater than 10% HLA expression were considered positive. Agreement statistics (κ) and Fisher’s exact test were used for analysis. Results: 51 patients with paired primary NSCLC and brain lesions were identified. The median HLA expression was 20% in the primary tumors (IQR 0-65%) and 10% in the brain metastases (IQR 5-40%). 27 primary tumors and 24 brain metastases were positive for HLA expression. There was disagreement in HLA positivity between paired lesions in 11 patients (22%, 95% CI 12-35%)(κ = 0.57, 95% CI 0.35-0.79)(p = 0.0001). There was no significant difference in the time between the primary tumor and brain metastasis resections in patients with HLA expression disagreement compared to those with HLA expression agreement. None of the patients received immune checkpoint inhibitors for treatment of these lesions. Conclusions: We found significant differences in HLA-A expression on tumor cells in nearly one quarter of paired primary lung cancers and brain metastases. Differences in HLA expression may help explain the discrepancies in response to immune checkpoint inhibitors at different sites of disease and warrants further study.

scholarly journals THER-14. INFLUENCE OF CLINICAL PARAMETERS ON THE EFFICACY OF IMMUNE CHECKPOINT INHIBITORS IN PATIENTS WITH NON-SMALL CELL LUNG CANCER BRAIN METASTASES (NSCLCBM)

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i13-i13
Author(s):  
Adam Lauko ◽  
Bicky Thapa ◽  
Baha’eddin Muhsen ◽  
Hamid Borghei-Razavi ◽  
Wei Wei ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
P Value ◽  
Small Cell Lung

Abstract INTRODUCTION: Non-small cell lung cancer brain metastases (NSCLCBM) patients have a dismal prognosis. Immune checkpoint inhibitors (ICI) have resulted in improved outcomes in a subset of patients, although limited information exists on the impact of ICI in patients with NSCLCBM. METHODS: We reviewed 121 NSCLCBM (2012–2018) patients treated at our tertiary care center. All patients received at least 2 cycles of ICI therapy after diagnosis of NSCLCBM. Overall survival (OS) and progression-free survival (PFS) were calculated from the start of ICI therapy to date of death, progression or last follow up. Kaplan-Meier curves were used to estimate survival and were analyzed using the Wilcoxon test. RESULTS: Median age was 62 years (39–81) and median KPS was 90. Eighty-six patient received Nivolumab, 7 Atezolizumab, 25 Pembrolizumab, and 3 patients received multiple ICI over the course of their treatment for NSCLCBM. One hundred and twelve patients underwent stereotactic radiosurgery. Nine patients were treated with ICI alone and 25 patients underwent surgical resection. Median OS for the entire cohort was 558 (303–1159) days and median PFS was 220 (114–512) days. Twenty-four patients received oral steroids within the first 28 days of ICI (median prednisone equivalent dose of 27 mg). Patients on upfront steroid therapy had a median PFS of 148 days vs 301 days in patients not on upfront steroids (p-value .0095). Complete blood count at the start of ICI was available for 87 patients and neutrophil to lymphocyte ratios (NLR) were calculated. Patients with NLR at the start of ICI above 5 (n=33) had a median overall survival of 337 days compared to 558 days when NLR was below 5 (p-value .038). CONCLUSION: Use of steroids at initiation or within first 28 days of ICI therapy and NLR of greater than 5 are associated with worse outcomes in NSCLCBM treated with ICI.

Efficacy of immune checkpoint inhibitors in non-small cell lung cancer patients with different metastatic sites: A systematic review and meta-analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21684-e21684
Author(s):  
Kaili Yang ◽  
Lin Zhao ◽  
Jiarui Li ◽  
Chunmei Bai
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Liver Metastases ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Metastatic Sites ◽  
Nsclc Patients

e21684 Background: Previous studies have demonstrated that bone, brain and liver metastases are poor prognosis factors of immune checkpoint inhibitors (ICIs) therapy in patients with non-small-cell lung cancer (NSCLC). This study aims to compare the efficacy of ICIs with conventional therapy in NSCLC patients with bone, brain or liver metastases. Methods: MEDLINE, Embase and CENTRAL were searched for prospective studies comparing ICIs with conventional therapy in NSCLC patients with bone, brain or liver metastases. Quality assessment was performed using the Newcastle-Ottawa Scale. The pooled hazard ratio (HR) of overall survival (OS) and progression-free survival (PFS) among included studies was analyzed using the random-effects model. Results: From 1,195 relevant articles, eight studies with high methodological quality consisting of 988 patients were included in the analysis. ICIs significantly improved OS for patients with brain metastases (HR = 0.57; 95%CI: 0.37-0.86; P = 0.007). Among patients with liver metastases, OS (HR = 0.72; 95%CI: 0.57-0.91; P = 0.006) and PFS (HR = 0.72; 95%CI: 0.49-0.87; P = 0.004) improvement was observed in the ICI treatment arm. No available study with bone metastases information was identified. Subgroup analysis revealed that PD-1 inhibitors could benefit patients on OS and PFS regardless of metastatic sites. Sensitivity analysis indicated good stability of this analysis. No obvious heterogeneity or publication bias was detected. Conclusions: ICIs could significantly improve OS in patients with brain metastases and both OS and PFS in patients with liver metastases. Although brain and liver metastases are generally regarded as poor prognostic factors for immunotherapy, this study still indicates ICIs are effective therapeutic options for NSCLC patients with these metastatic sites.

scholarly journals Immunotherapy in Non-Small Cell Lung Cancer Patients with Brain Metastases: Clinical Challenges and Future Directions

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3407
Author(s):  
Ranjan Pathak ◽  
Arya Amini ◽  
Addie Hill ◽  
Erminia Massarelli ◽  
Ravi Salgia
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancer Patients

Immune checkpoint inhibitors have revolutionized the treatment landscape for patients with non-small cell lung cancers. Existing treatment paradigms for brain metastases in lung cancer patients leave patients with adverse neurocognitive function, poor quality of life, and dismal prognosis, thus highlighting the need to develop more effective systemic therapies. Although data are limited, emerging knowledge suggests promising activity and safety of immune checkpoint inhibitors in brain metastases in non-small cell lung cancer patients. This review aims to summarize the current data, highlight the challenges of incorporating immune checkpoint inhibitors in treating these patients, and identify areas for future research.

scholarly journals Immune checkpoint inhibitors for brain metastases in non-small-cell lung cancer: from rationale to clinical application

Immunotherapy ◽  
2021 ◽  
Author(s):  
Gang Xiao ◽  
Zhiyuan Liu ◽  
Xuan Gao ◽  
Han Wang ◽  
Haiqin Peng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Clinical Data ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

Brain metastases (BM) is common in non-small-cell lung cancer (NSCLC) patients. Immune checkpoint inhibitors (ICIs) have gradually become a routine treatment for NSCLC BM patients. Currently, three PD-1 inhibitors (pembrolizumab, nivolumab and cemiplimab), one PD-L1 inhibitor (atezolizumab) and one CTLA-4 inhibitor (ipilimumab) have been approved for the first-line treatment of metastatic NSCLC. It is still controversial whether PD-L1, tumor infiltrating lymphocytes, and tumor mutation burden can be used as predictive biomarkers for immune checkpoint inhibitors in NSCLC patients with BM. In addition, clinical data on NSCLC BM were inadequate. Here, we review the theoretical basis and clinical data for the application of ICIs in the therapy of NSCLC BM.

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