monitoring-pd-1-blocking-antibodies-bound-to-t-cells-derived-from

Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood

Immune checkpoint inhibitors, including PD-1&#8211;blocking antibodies, have significantly improved treatment outcomes in various types of cancer. The ...

Osaka University Graduate School of Medicine

Most of nonsmall cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) activating mutations eventually acquire resistance to the first EGFR-tyrosine kinase inhibitors (TKIs) therapy after varying periods of treatment. Of note, approximately one-third of those patients develop brain metastases, which deteriorate their quality of life and survival. The effect of systemic chemotherapy on brain metastases after acquisition of EGFR-TKI resistance is limited, and thus far, whole-brain radiation therapy, which may cause the harmful effect on neurocognitive functions, has been the only established therapeutic option for especially symptomatic brain metastases. Osimertinib is a third-generation oral, potent, and irreversible EGFR-TKI. It can bind to EGFRs with high affinity even when the EGFR T790M mutation exists in addition to the sensitizing mutations. Its clinical efficacy for NSCLC patients harboring the T790M mutation has already been shown; however, the evidence of osimertinib on brain metastases has not been documented well, especially in terms of the appropriate timing for treatment and its response evaluation.

Rapid intracranial response to osimertinib, without radiotherapy, in nonsmall cell lung cancer patients harboring the EGFR T790M mutation: Two Case Reports.

The efficacy and safety of chemotherapy for patients with lung cancer who are in need of intensive care, such as invasive mechanical ventilation, have not been established.

[A Case of Mediastinal Small Cell Lung Cancer in a Patient Receiving Mechanical Ventilation Who Was Successfully Treated with Chemotherapy and Finally Extubated].

The PD-1-blocking antibody nivolumab persists in patients several weeks after the last infusion. However, no study has systematically evaluated the maximum duration that the antibody persists on T cells or the association between this duration and residual therapeutic efficacy or potential adverse events.

Clinical implications of monitoring nivolumab immunokinetics in non-small cell lung cancer patients.

Recent clinical trials have demonstrated that anti-PD-1 blocking antibodies showed remarkable clinical efficacy in a subset of non-small cell lung cancer (NSCLC) patients. Clinical trials usually exclude patients with renal dysfunction who are receiving hemodialysis (HD). Therefore, it is unclear whether these patients can be safely and effectively treated with pembrolizumab. Here, we present a non-small cell lung cancer patient on HD who achieved complete remission after one dose of pembrolizumab without severe adverse events. We assessed pembrolizumab binding to peripheral blood T cells in this patient using a method that we recently developed. This is the first report to visualize pembrolizumab binding to T cells in a patient on HD during and after pembrolizumab treatment. The pharmacokinetics of pembrolizumab in this case were similar to those in patients with normal renal function, suggesting that severe renal dysfunction has little influence on the metabolism of pembrolizumab, and is not a contraindication for anti-PD-1 treatment. Immune checkpoint inhibitors, including pembrolizumab, may be a vital therapeutic option for lung cancer patients on HD.

Article	Year
Rapid intracranial response to osimertinib, without radiotherapy, in nonsmall cell lung cancer patients harboring the EGFR T790M mutation: Two Case Reports. Medicine\| PubMed ID: 28178168	2017
[A Case of Mediastinal Small Cell Lung Cancer in a Patient Receiving Mechanical Ventilation Who Was Successfully Treated with Chemotherapy and Finally Extubated]. Gan to kagaku ryoho. Cancer & chemotherapy\| PubMed ID: 30237376	2018
Clinical implications of monitoring nivolumab immunokinetics in non-small cell lung cancer patients. JCI insight\| PubMed ID: 30282824	2018
Monitoring antibody binding to T cells in a pembrolizumab-treated patient with lung adenocarcinoma on hemodialysis. Thoracic cancer\| PubMed ID: 31520515	2019

Yujiro Naito

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