According to a study published in natural medicine.
“The results of this study will help us identify and design better blood biomarkers in immuno-oncology,” said Young Kwang Chae, MD, MPH, MBA, associate professor of medicine in the Division of Hematology and Oncology and co-author of the study.
Atezolizumab monotherapy, an immune checkpoint therapy, is an effective treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors exhibit elevated expression of the programmed death ligand 1 (PD-L1). When PD-L1 is bound on the outside of a cell, it tells roaming T cells to leave the cell alone. Many cancers have upregulated PD-L1 to help hide cancer cells from the immune system.
However, a biopsy is required to determine PD-L1 levels, and up to 30 percent of patients with NSCLC may not have enough high-quality tissue biopsied at diagnosis for accurate biomarker analyses, according to Chae.
“We often encounter the problem of insufficient tissue samples to perform biomarker analysis in lung cancer, so it is important to develop a blood biomarker that predicts response to immunotherapy,” said Chae, who is also a fellow from Robert H. Lurie. Northwestern University Comprehensive Cancer Center.
In the trial, which recruited 153 patients with NSCLC, researchers analyzed circulating tumor DNA (ctDNA) for tumor mutation load (TMB), a measure of the total mutations found in the DNA of cancer cells. High TMB cancers have been associated with a positive response to immune checkpoint inhibitor treatments.
Of the patients, 28 had high TMB values - making them suitable for atezolizumab monotherapy – while 91 patients had low TMB values. Notably, the high BMR group was slightly younger and had more smokers.
All patients received atezolizumab as monotherapy and treatment response rates were much higher in the high TMB group – 35.7% compared to only 5.5% in the low TMB group. Patients in the high TMB group also experienced longer survival than those in the low TMB group.
The results demonstrate that measuring TMB in ctDNA is a viable option to stratify patients for immune checkpoint inhibitor treatment, according to the authors. Although more work is needed to understand the relationship between TMB and immune checkpoint inhibitor therapy – hopefully revealing a subpopulation of patients who would benefit most from therapy – the basis for selection therapy using a simple blood test are solid, according to Chae.
“This will allow the right therapy to be delivered to the right group of patients,” Chae said.
This study was supported by F. Hoffmann-La Roche.
Chae has received research grants from AbbVie, Bristol Myers Squibb, Biodesix, Lexent Bio and Freenome and honoraria to serve on advisory boards from Roche/Genentech, Bristol Myers Squibb, AstraZeneca, Merck, Foundation Medicine, Counsyl, Neogenomics, Guardant Health, Boehringher Ingelheim, Biodesix, ImmuneOncia, Lilly Oncology, Merck, Takeda, Pfizer, Tempus, Lunit and Jazz Pharmaceuticals.
Reference: Kim ES, Velcheti V, Mekhail T, et al. Blood-based tumor mutational load as a biomarker of atezolizumab in non-small cell lung cancer: the phase 2 B-F1RST trial. NatMed. 2022;28(5):939-945. doi:10.1038/s41591-022-01754-x
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