Dramatic Response of Leptomeningeal Carcinomatosis to Nivolumab in PD-L1 Highly Expressive Non-small Cell Lung Cancer: A Case Report

Ron, David Arias; Labandeira, Carmen M.; Manrique, Maria Carmen Areses; Domarco, Paula Sampedro; Abdulkader, Ihab; García-Mata, Jesús; Rolfo, Christian; González-Rivas, Diego; Fírvida, J. L.

doi:10.3389/fonc.2019.00819

Cited by 13 publications

(8 citation statements)

References 38 publications

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“…The search yielded 289 citations, of which 14 were included in the qualitative synthesis (Supplementary File 1). Nine were case-reports, four were retrospective case-series (including 32 patients), and one was a single-arm phase-II trial (including 20 patients); levels of evidence were V, IV, and IIb, respectively (Supplementary File 2) (8)(9)(10)(11)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). Critical appraisal resulted in low risk of bias for all included articles (Supplementary File 3).…”

Section: Resultsmentioning

confidence: 99%

“…Accordingly, most of our pooled patients presented with headache, vomiting, and cranial-nerve palsies, but available data on hydrocephalus were scarce. In two singular cases, memory loss and auditory hallucinations were ascribed to the presence of temporoinsular LMD lesions (8,21). Most LMD diagnoses were obtained after new symptom onset or upon routine followup surveillance in patients with metastatic disease.…”

Section: Discussionmentioning

confidence: 99%

“…Contrarily, mild radiotherapy adverse events (hair loss and skin reactions) occur in approximately 100% of patients, posing a significant cosmetic burden and affecting quality of life (3,37). Severe ICI-related adverse-events (headache, bone marrow depression) were reported in 5 patients (15.6%) but were successfully treated with temporary ICI discontinuation and/or addition of steroids (8,9,24). Of note, the use of steroids for mitigating ICI-related adverse events has not been correlated with a negative impact on survival (59).…”

Section: Discussionmentioning

confidence: 99%

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The Role of Immune Checkpoint Inhibitors in Leptomeningeal Disease: A Systematic Review

et al. 2021

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The Role of Immune Checkpoint Inhibitors in Leptomeningeal Disease: A Systematic Review

et al. 2021

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“…Among those drugs and therapies, programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) blockade was proved to be novel cancer immunotherapies for cancers treatment, and the associated drugs were developed to treat NSCLC in clinic [ 6 , 7 ]. These therapeutic drugs included PD-1 inhibitors Nivolumab (Opdivo) [ 8 , 9 ] as well as Pembrolizumab (Keytruda) [ 10 , 11 ], and PD-L1 inhibitors Atezolizumab (Tecentriq) [ 12 ], Durvalumab (Imfinzi) [ 13 ] and Avelumab (Bavencio) [ 14 ]. Previous data indicated that cancer cells derived PD-L1 regulated the activity of CD8 + T cell activity [ 15 , 16 ], which was a pivotal component of the cellular immune response in tumor development [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Circular RNA circ-CPA4/ let-7 miRNA/PD-L1 axis regulates cell growth, stemness, drug resistance and immune evasion in non-small cell lung cancer (NSCLC)

Hong

Xue

Jiang

et al. 2020

J Exp Clin Cancer Res

251

194

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Background Non-small cell lung cancer (NSCLC) cells derived intracellular and extracellular programmed cell death ligand 1 (PD-L1) promoted cancer progression and drug resistance, and facilitated tumor immune evasion. However, the detailed molecular mechanisms are still largely unknown. In the present study, we aimed to explore the role of circular RNA circ-CPA4/let-7 miRNA/PD-L1 axis in the regulation of NSCLC progression, drug resistance and tumor immune microenvironment. Methods Real-Time qPCR and Western Blot analysis were conducted to examine gene expressions at transcriptional and translated levels, respectively. The regulatory mechanisms of circ-CPA4, let-7 miRNA and PD-L1 were validated by dual-luciferase reporter gene system and RNA pull-down assay. Cell growth and apoptosis were determined by CCK-8 assay, colony formation assay and Annexin V-FITC/PI double staining assay. Cell mobility was evaluated by transwell assay. Results Circ-CPA4 and PD-L1 were high-expressed, while let-7 miRNA was low-expressed in NSCLC cells and cancer tissues compared to the human bronchial epithelial (HBE) cells and their paired clinical normal adjacent tissues, respectively. Besides, knock-down of circ-CPA4 inhibited cell growth, mobility and epithelial-mesenchymal transition (EMT), and promoted cell death in NSCLC cells by downregulating PD-L1 through serving as a RNA sponge for let-7 miRNA. In addition, the NSCLC cells derived PD-L1-containing exosomes promoted cell stemness and increased resistance of NSCLC cells to cisplatin. Notably, by co-culturing the NSCLC cells with CD8 + T cells isolated from human peripheral blood mononuclear cells (hPBMCs) in a transwell co-culturing system, we found that NSCLC cells inactivated CD8 + T cells in a secreted PD-L1-dependent manner. Further results suggested that circ-CPA4 also positively regulated exosomal PD-L1, and the NSCLC cells with circ-CPA4 ablation re-activated CD8 + T cells in the co-culturing system. Conclusion Taken together, circ-CPA4 regulated cell growth, mobility, stemness and drug resistance in NSCLC cells and inactivated CD8 + T cells in the tumor immune microenvironment through let-7 miRNA/PD-L1 axis.

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“…Therefore, we have a hypothesis that whether SMARCA4m could be a predictor for ICIs response in NSCLC. Notably, there was one previous report that showed that PD-1 inhibitor was effective for a SMARCA4 deficient NSCLC patient with a high TMB and PD-L1 not highly expressed [9]. However, there was another study that reported hyperprogressive disease was obtained after immune checkpoint inhibitor treatment in SMARCA4 deficient SCLC [10].…”

Section: Discussionmentioning

confidence: 99%

Extremely Rapid Response to Pembrolizumab in a SMARCA4 Mutant PD-L1 Highly Expressive Advanced Lung Adenocarcinoma: A Case Report

Liu¹,

Zhu²,

Pan³

2021

SCR

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SMARCA4 mutant non-small cell lung cancer (SMARCA4m-NSCLC) has a poor prognosis owing to rapid growth. Effective treatments for SMARCA4m-NSCLC have not yet been established. Recently, many preclinical studies support the hypothesis that SMARCA4m-NSCLC may be vulnerable to immune checkpoint inhibitors. Here, we report a patient with programmed death-ligand1 (PD-L1) highly expressive SMARCA4m-NSCLC who showed an extremely rapid and long-term response to pembrolizumab. He was referred to our hospital for a mass of the right lung. Positron emission tomography-computed tomography showed right lung tumor, hilar, mediastinal and bone metastases. Pathological and immunohistochemical results showed it was a lung adenocarcinoma and revealed the tumor proportion score of PD-L1 was 80%. SMARCA4 and K-RAS genes were co-mutations. BRG1 protein expression was negative. Subsequently, pembrolizumab treatment as the first line of therapy was commenced for the patient. With only one dose, pembrolizumab significantly inhibited tumor growth and a partial response was obtained. To date, pembrolizumab treatment has been continued for about 29 months. Severe immune-related adverse events were not observed. Our case showed that an extremely rapid and long-term response can be achieved with pembrolizumab for PD-L1 highly expressive SMARCA4m-NSCLC. Immune checkpoint inhibitors treatment may be a promising strategy for PD-L1 positive SMARCA4m-NSCLC.

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Dramatic Response of Leptomeningeal Carcinomatosis to Nivolumab in PD-L1 Highly Expressive Non-small Cell Lung Cancer: A Case Report

Cited by 13 publications

References 38 publications

The Role of Immune Checkpoint Inhibitors in Leptomeningeal Disease: A Systematic Review

The Role of Immune Checkpoint Inhibitors in Leptomeningeal Disease: A Systematic Review

Circular RNA circ-CPA4/ let-7 miRNA/PD-L1 axis regulates cell growth, stemness, drug resistance and immune evasion in non-small cell lung cancer (NSCLC)

Extremely Rapid Response to Pembrolizumab in a SMARCA4 Mutant PD-L1 Highly Expressive Advanced Lung Adenocarcinoma: A Case Report

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