Can tumor mutation burden be used as a predictive biomarker to immune checkpoint inhibitors for non-small cell lung cancer?

This article looked at the use of tumor mutation burden (TMB) to predict response to immune checkpoint inhibitor (ICI) therapy in patients with non-small cell lung cancer (NSCLC). The authors found that TMB is a promising biomarker that can predict the effectiveness of ICI therapy in advanced NSCLC. 

NSCLC represents around 85% of all lung cancer diagnoses. Standard care usually involves chemotherapy, radiotherapy, and surgery or a combination of all of them. Despite this, advanced NSCLC can be difficult to treat with a poor prognosis. New therapeutics such as ICIs can be effective in treating advanced NSCLC.

ICIs are immunotherapies. They block certain proteins on cancer cells that can weaken the immune response towards the cancer. Therefore, ICIs allow the immune cells to better detect and kill cancer cells. Previous studies have investigated the use of ICIs in the treatment of NSCLC and they have been found to be effective as a therapy. The problem occurs with finding which patients will have a good response to an ICI.

TMB refers to the number of mutations (genetic changes) found in cancerous cells. There is evidence that supports the use of TMB as a predictive biomarker for response to ICIs. TMB has the advantage over other biomarkers in that it can be obtained in blood samples. A summary of TMB use in NSCLC ICI therapy has not previously been carried out. 

This study analyzed the results of 14 articles where TMB was analyzed in patients receiving ICIs for NSCLC. Overall, 2872 patients were included.       

7 studies with 515 NSCLC were used to assess the relationship between TMB and the response to ICIs. In a high-TMB group, the ORR to ICI therapy was 3.52 times higher when compared to a low TMB group. 

4 studies with 278 patients looked at the relationship between TMB and the percentage of patients who achieved disease control (tumor does not grow or spread). Patients with a high TMB were 3.26 times more likely to achieve disease control with ICI therapy compared to those in a low TMB group. 

11 studies with 1688 patients assessed the relationship between survival of patients without disease progression and TMB. There was a 19% increased chance of survival without disease progression in the high-TMB group compared to the low-TMB group with ICI use. 

7 studies with 2110 NSCLC patients showed that the overall survival of patients taking an ICI with a high TMB was 17% higher than patients with a low TMB. 

The authors concluded that TMB can be used as a biomarker to predict the effectiveness of ICIs in patients with NSCLC.