Corticosteroid administration for cancer-related indications is an unfavorable prognostic factor in solid cancer patients receiving immune checkpoint inhibitor treatment

2021 ◽  
Vol 99 ◽  
pp. 108031
Author(s):  
Ying Wang ◽  
Mengxue Yang ◽  
Mingyang Tao ◽  
Peipei Liu ◽  
Cheng Kong ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Solid Cancer ◽  
Corticosteroid Administration ◽  
Unfavorable Prognostic Factor ◽  
Inhibitor Treatment

scholarly journals Soluble PD-L1 is a predictive and prognostic biomarker in advanced cancer patients who receive immune checkpoint blockade treatment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
So Yeon Oh ◽  
Soyeon Kim ◽  
Bhumsuk Keam ◽  
Tae Min Kim ◽  
Dong-Wan Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Prognostic Factor ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Progressive Disease ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Checkpoint Inhibitor Therapy

AbstractCirculating soluble programmed death-1 ligand (sPD-L1) is measurable in the serum of cancer patients. This study aimed to investigate the significance of sPD-L1 in cancer patients receiving immune checkpoint inhibitor therapy. Blood samples were obtained before and after immune checkpoint inhibitor therapy (January 2015 to January 2019). The study cohort consisted of 128 patients who were diagnosed with non-small cell lung cancer (n = 50), melanoma (n = 31), small cell lung cancer (n = 14), urothelial carcinoma (n = 13), and other cancers (n = 20). Patients with a high level (> 11.0 pg/μL) of sPD-L1 were more likely to exhibit progressive disease compared with those with a low level (41.8% versus 20.7%, p = 0.013). High sPD-L1 was also associated with worse prognosis; the median PFS was 2.9 (95% confidence interval [CI] 2.1–3.7) months versus 6.3 (95% CI 3.0–9.6) months (p = 0.023), and the median OS was 7.4 (95% CI 6.3–8.5) months versus 13.3 (95% CI 9.2–17.4) months (p = 0.005). In the multivariate analyses, high sPD-L1 was an independent prognostic factor for both decreased PFS (HR 1.928, p = 0.038) and OS (HR 1.788, p = 0.004). sPD-L1 levels did not correlate with tissue PD-L1 expression. However, sPD-L1 levels were positively correlated with neutrophil to lymphocyte ratios and negatively correlated with both the proportion and the total number of lymphocytes. We found that high pretreatment sPD-L1 levels were associated with progressive disease and were an independent prognostic factor predicting lower PFS and OS in these patients.

scholarly journals Case series of cancer patients who developed cholecystitis related to immune checkpoint inhibitor treatment

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Hamzah Abu-Sbeih ◽  
Cynthia Nguyen Tran ◽  
Phillip S. Ge ◽  
Manoop S. Bhutani ◽  
Mazen Alasadi ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Case Series ◽  
Inhibitor Treatment

scholarly journals Identification of NOTCH4 mutation as a response biomarker for immune checkpoint inhibitor therapy

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Junyu Long ◽  
Dongxu Wang ◽  
Xu Yang ◽  
Anqiang Wang ◽  
Yu Lin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Bladder Cancer ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Esophagogastric Cancer ◽  
Clinical Benefits

Abstract Background Immune checkpoint inhibitor (ICI) therapy elicits durable antitumor responses in patients with many types of cancer. Genomic mutations may be used to predict the clinical benefits of ICI therapy. NOTCH homolog-4 (NOTCH4) is frequently mutated in several cancer types, but its role in immunotherapy is still unclear. Our study is the first to study the association between NOTCH4 mutation and the response to ICI therapy. Methods We tested the predictive value of NOTCH4 mutation in the discovery cohort, which included non-small cell lung cancer, melanoma, head and neck squamous cell carcinoma, esophagogastric cancer, and bladder cancer patients, and validated it in the validation cohort, which included non-small cell lung cancer, melanoma, renal cell carcinoma, colorectal cancer, esophagogastric cancer, glioma, bladder cancer, head and neck cancer, cancer of unknown primary, and breast cancer patients. Then, the relationships between NOTCH4 mutation and intrinsic and extrinsic immune response mechanisms were studied with multiomics data. Results We collected an ICI-treated cohort (n = 662) and found that patients with NOTCH4 mutation had better clinical benefits in terms of objective response rate (ORR: 42.9% vs 25.9%, P = 0.007), durable clinical benefit (DCB: 54.0% vs 38.1%, P = 0.021), progression-free survival (PFS, hazard ratio [HR] = 0.558, P < 0.001), and overall survival (OS, HR = 0.568, P = 0.006). In addition, we validated the prognostic value of NOTCH4 mutation in an independent ICI-treated cohort (n = 1423). Based on multiomics data, we found that NOTCH4 mutation is significantly associated with enhanced immunogenicity, including a high tumor mutational burden, the expression of costimulatory molecules, and activation of the antigen-processing machinery, and NOTCH4 mutation positively correlates activated antitumor immunity, including infiltration of diverse immune cells and various immune marker sets. Conclusions Our findings indicated that NOTCH4 mutation serves as a novel biomarker correlated with a better response to ICI therapy.

Rheumatoid arthritis and polymyalgia rheumatica occurring after immune checkpoint inhibitor treatment

2017 ◽  
Vol 76 (10) ◽  
pp. 1747-1750 ◽  
Author(s):  
Rakiba Belkhir ◽  
Sébastien Le Burel ◽  
Laetitia Dunogeant ◽  
Aurélien Marabelle ◽  
Antoine Hollebecque ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Checkpoint ◽  
Polymyalgia Rheumatica ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Inhibitor Treatment

Fr507 IMMUNE CHECKPOINT INHIBITOR RESUMPTION IS ASSOCIATED WITH BETTER LONG TERM OUTCOMES IN CANCER PATIENTS

2021 ◽  
Vol 160 (6) ◽  
pp. S-337
Author(s):  
Fangwen Zou ◽  
Anusha Shirwaikar Thomas ◽  
Barbara E. Dutra ◽  
Shruti Khurana ◽  
Isabella C. Glitza Oliva ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Long Term Outcomes

“Restlessness” After Cancer Diagnosis and Treatment

2021 ◽  
pp. 157-159
Author(s):  
Anastasia Zekeridou
Keyword(s):  
Cerebrospinal Fluid ◽  
Cancer Diagnosis ◽  
Immunoglobulin G ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Hyperkinetic Movement Disorder ◽  
Phosphodiesterase 10A ◽  
Cancer Remission ◽  
Inhibitor Treatment

A 76-year-old woman sought care for unintentional weight loss, hematuria, and fatigue. She was diagnosed with plurimetastatic renal cell carcinoma. After resection of the primary tumor and metastases, she was treated with pembrolizumab, an immune checkpoint inhibitor. The patient experienced involuntary tongue and face movements with dysphagia and weight loss. She was also described as “restless.” At that point, the patient was in cancer remission with ongoing immune checkpoint inhibitor treatment. Blood testing was unremarkable. Brain magnetic resonance imaging showed basal ganglia T2/fluid-attenuated inversion recovery hyperintensities without gadolinium enhancement. Cerebrospinal fluid testing showed slightly increased protein concentration and 8 cerebrospinal fluid-restricted oligoclonal bands. Serum and cerebrospinal fluid testing for neural autoantibodies showed immunoglobulin G immunoreactivity in a mouse tissue indirect immunofluorescence assay, predominantly staining the basal ganglia. The immunoglobulin G was subsequently identified to bind to phosphodiesterase 10A. The patient was diagnosed with paraneoplastic phosphodiesterase 10A-immunoglobulin G autoimmunity manifesting as hyperkinetic movement disorder triggered by immune checkpoint inhibitor treatment. Given the patient’s cancer remission, the immune checkpoint inhibitor treatment was discontinued. She was treated with high-dose intravenous corticosteroids, with improvement of her hyperkinetic movement disorder but persistence of some dystonic movements. Further treatment with oral prednisone did not produce further improvement. The patient was treated symptomatically with onabotulinumtoxinA injections and tetrabenazine, which ameliorated her dystonic movements. Three years after her cancer diagnosis, she was alive and in cancer remission with minimal residual movements. Immune checkpoint inhibitors are monoclonal antibodies targeting “stop signs” of the immune response, which lead to enhanced endogenous responses, including those against cancer. Autoimmune complications are consequences of the enhanced immunity and can affect all organs, including the nervous system.

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