Are immune checkpoint blockade monoclonal antibodies active against CNS metastases from NSCLC?—current evidence and future perspectives

O’Kane, Grainne M.

doi:10.21037/tlcr.2016.09.05

Cited by 16 publications

(11 citation statements)

References 99 publications

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“…This organ-specific response may be the result of the different PD-L1 expression, microenvironment and genetic heterogeneity profiles between primary and metastatic sites. Many retrospective analyses on NSCLC and melanoma patients with liver metastases, treated with ICIs, experienced notably poorer response rates and survival outcomes [30,31]. The liver is characterized by an immune-suppressive microenvironment where IL-10-secreting dendritic cells, Kupffer macrophages and sinusoidal endothelial cells may induce T-cell anergy and decreased likelihood of response to immunotherapy alone [32,33].…”

Section: Discussionmentioning

confidence: 99%

“…Our analysis showed the negative prognostic role of liver metastases, while the survival impact of bone and brain metastases remains still uncertain. Brain metastases are not confirmed as a negative prognostic factor because ICIs may cross the blood-brain barrier and induce disease response in selected patients [31]. Data from both retrospective series [36] and clinical trials showed good activity of ICIs as a single agent [37] or in combination with chemotherapy [38] in patients with brain metastases.…”

Section: Discussionmentioning

confidence: 99%

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EPSILoN: A Prognostic Score for Immunotherapy in Advanced Non-Small-Cell Lung Cancer: A Validation Cohort

Prelaj

Ferrara

Rebuzzi

et al. 2019

Cancers

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Background: Beyond programmed death ligand 1 (PD-L1), no other biomarkers for immunotherapy are used in daily practice. We previously created EPSILoN (Eastern Cooperative Oncology Group performance status (ECOG PS), smoking, liver metastases, lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR)) score, a clinical/biochemical prognostic score, in 154 patients treated with second/further-line immunotherapy. This study’s aim was to validate EPSILoN score in a different population group. Methods: 193 patients were included at National Cancer Institute of Milan (second-line immunotherapy, 61%; further-line immunotherapy, 39%). Clinical/laboratory parameters such as neutrophil-to-lymphocyte ratio and lactate dehydrogenase levels were collected. Kaplan–Meier and Cox hazard methods were used for survival analysis. Results: Overall median progression-free survival and median overall survival were 2.3 and 7.6 months, respectively. Multivariate analyses for Progression-Free Survival (PFS) identified heavy smokers (hazard ratio (HR) 0.71, p = 0.036) and baseline LDH < 400 mg/dL (HR 0.66, p = 0.026) as independent positive factors and liver metastases (HR 1.48, p = 0.04) and NLR ≥ 4 (HR 1.49, p = 0.029) as negative prognostic factors. These five factors were included in the EPSILoN score which was able to stratify patients in three different prognostic groups, high, intermediate and low, with PFS of 6.0, 3.8 and 1.9 months, respectively (HR 1.94, p < 0.001); high, intermediate and low prognostic groups had overall survival (OS) of 24.5, 8.9 and 3.4 months, respectively (HR 2.40, p < 0.001). Conclusions: EPSILoN, combining five baseline clinical/blood parameters (ECOG PS, smoking, liver metastases, LDH, NLR), may help to identify advanced non-small-cell lung cancer (aNSCLC) patients who most likely benefit from immune checkpoint inhibitors (ICIs).

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

EPSILoN: A Prognostic Score for Immunotherapy in Advanced Non-Small-Cell Lung Cancer: A Validation Cohort

Prelaj

Ferrara

Rebuzzi

et al. 2019

Cancers

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“…Whether ICPis affect brain metastasis remains unclear (6,7). Some prospective trials are currently being conducted, and the results of a phase 2 trial of pembrolizumab for melanoma and NSCLC with brain metastasis (8) indicate that the brain lesions were responsive in 6 of 18 patients with NSCLC.…”

Section: Discussionmentioning

confidence: 99%

Pembrolizumab-induced autoimmune encephalitis in a patient with advanced non-small cell lung cancer: A case report

et al. 2018

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Immune checkpoint inhibitors have markedly changed lung cancer treatment and improved overall survival. However, immune checkpoint inhibitors may be associated with various adverse events, including encephalitis, although this complication is rare. We herein describe the clinical characteristics of a case of immune checkpoint inhibitor-induced encephalitis and its management. A 51-year-old man with squamous non-small cell lung cancer was receiving pembrolizumab treatment when he suddenly displayed an altered level of consciousness. Cerebrospinal fluid examination revealed elevated lymphocyte count and autoimmune encephalitis was suspected. The patient was promptly started on steroids and his consciousness immediately improved. Pembrolizumab treatment was discontinued; however, stable disease was maintained. In conclusion, encephalitis is a rare but possibly fatal adverse event of immune checkpoint inhibitors, and prompt diagnosis and treatment are mandatory.

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“…These approaches may also lead to the development of small molecule ICI approaches that can penetrate the blood brain barrier (BBB), enabling ICI to be applied to primary brain cancer or brain metastases that are not amenable to treatment with current antibody-based ICI therapies. (14)…”

Section: Small Molecules the Next Generation Immune Checkpoint Inhibmentioning

confidence: 99%

The Next Generation of Immunotherapy for Cancer: Small Molecules Could Make Big Waves

Kerr

Chisholm

2019

The Journal of Immunology

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After decades of intense effort, therapeutics that leverage the immune system to fight cancer have now been conclusively demonstrated to be effective. Immunoncology has arrived and will play a key role in the treatment of cancer for the foreseeable future. However, the search for novel methods to improve immune responses to cancer continues unabated. Towards this end, small molecules that can either reduce immune suppression in the tumor milieu or that enhance activation of cytotoxic lymphocyte responses to the tumor are actively being pursued. Such novel treatment strategies might be used as monotherapies or combined with other cancer therapies to increase and broaden their efficacy. Here we provide an overview of small molecule immunotherapeutic approaches for the treatment of cancer. Over the next decade and beyond, these approaches could further enhance our ability to harness the immune system to combat cancer and thus become additional weapons in the oncologist’s armory.

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Are immune checkpoint blockade monoclonal antibodies active against CNS metastases from NSCLC?—current evidence and future perspectives

Cited by 16 publications

References 99 publications

EPSILoN: A Prognostic Score for Immunotherapy in Advanced Non-Small-Cell Lung Cancer: A Validation Cohort

EPSILoN: A Prognostic Score for Immunotherapy in Advanced Non-Small-Cell Lung Cancer: A Validation Cohort

Pembrolizumab-induced autoimmune encephalitis in a patient with advanced non-small cell lung cancer: A case report

The Next Generation of Immunotherapy for Cancer: Small Molecules Could Make Big Waves

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