Blood Tumor Mutational Burden Could Identify Benefit from Checkpoint Inhibitors in NSCLC

A cancer gene panel using blood may be a cost-effective way of testing the quantity of mutations found in tumors of patients with non-small cell lung cancer.
BY Kristie L. Kahl
PUBLISHED March 13, 2019
Blood tumor mutational burden – which measures the quantity of mutations found in a tumor – may be a potential biomarker in identifying which patients with non-small cell lung cancer (NSCLC) could benefit from anti-PD-1 and anti-PD-L1 therapy, according to results published in JAMA Oncology.

Tumor mutational burden measured using tissue with whole-exome sequencing or a next-generation sequencing cancer gene panel already serves as an approach to determine clinical outcomes from immune checkpoint blockades in various cancer types. However, those with advanced disease tend to lack sufficient tissue material for molecular testing.

“Therefore, whether (tumor mutational burden) can be measured using circulating tumor DNA (namely, blood tumor mutational burden) as a noninvasive approach to guide immune checkpoint blockade therapies has attracted widespread attention from practitioners,” the researchers wrote.

Because the reliability of circulating tumor DNA detection is still under debate, the researchers aimed to explore the optimal gene panel size and algorithm to design a cancer gene panel for tumor mutational burden estimation, called NCC-GP150, and further evaluated its reliability and validated its feasibility of blood tumor mutational burden as a biomarker for immunotherapy use in patients with NSCLC.

Tumor mutational burden was evaluated in matched blood and tissue samples from 48 patients with advanced NSCLC (average age, 60 years; female, 31.2 percent), while an independent cohort of 50 patients with the disease (average age, 58 years; female, 30.0 percent) was also used to identify the utility of blood tumor mutational burden – estimated using NCC-GP150 – in determining which patients would benefit from anti-PD-1 and anti-PD-L1 therapy.

The researchers found that NCC-GP150 was a cost-effective panel for tumor mutational burden estimation with satisfactory performance.

Blood tumor mutational burden estimated by NCC-GP150 correlated well with tissue tumor mutational burden calculated by whole-exome sequencing. In addition, a blood tumor mutational burden of six or higher was associated with superior progression-free survival (the time from treatment to disease worsening) and objective response rates in patients treated with anti-PD-1 and anti-PD-L1 therapy.

“Our findings suggest that NCC-GP150, a panel through rational design on TCGA (The Cancer Genome Atlas), could be used for (blood tumor mutational burden) estimation as a surrogate for (tissue)-based (tumor mutational burden),” the researchers wrote. “We also validated (blood tumor mutational burden) as a potential biomarker to identify patients with NSCLC who could obtain significant improvements from immunotherapy. Blood (tumor mutational burden) profiled with (circulating tumor) DNA sequencing is a promising strategy for (tumor mutational burden) and (immune checkpoint blockade) response estimation.”
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