Genomic profile products enhanced to better predict immunotherapy response

Foundation Medicine, based in Cambridge, Mass., announced in late August the addition of new clinical markers to its genomic profile products FoundationOne and FoundationOne Heme. The new products include integrated and validated assessments of tumor mutational burden (TMB) and Microsatellite Instability (MSI), in addition to the products’ existing gene profiling capabilities.

“Cancer immunotherapies are at the forefront of cancer treatment, and new, quantitative approaches are needed to predict clinical responses to this important, but also expensive, class of therapies,” Vincent Miller, M.D., chief medical officer of Foundation Medicine says in a press release. “Prior to our ability to measure TMB and MSI with FoundationOne, these biomarkers could only be detected separately, either through tests such as immunohistochemistry, polymerase chain reaction (PCR) or whole exome sequencing. Importantly, high-quality, predictive TMB scoring can only be accurately performed with sophisticated algorithms developed to work with broad, hybrid capture-based platforms that can analyze all relevant alterations simultaneously. Integrating this capability to measure TMB and MSI with one tissue sample, and reported in one test, represents an important advance in clinical care.”

Studies presented at this year’s American Society of Clinical Oncology (ASCO) annual meeting in June, suggest TMB predicts the likelihood of response to cancer immunotherapies. TMB, which is reported as the total number of DNA mutations per megabase in a tumor sequence, has been detected in different tumor types, including melanoma.

“Some tumors develop high TMB as a result of defective mismatch repair of DNA, a condition in which the length of certain DNA areas becomes more widely varied than normal,” according to the release. “This condition, which is referred to as MSI-high and MSI-high tumors, almost always has a high TMB.”

In a study on melanoma presented at ASCO, researchers used Hybrid Capture-Based Next Generation Sequencing (HC NGS) to identify markers of response to anti-PD-1/PD-L1. Study author Douglas Buckner Johnson, M.D., of Vanderbilt University Medical Center, is quoted in ASCO Daily News as saying the mutational load as determined by this platform “may aid in treatment stratification.”

The researchers performed HC NGS on 236-315 genes on archival samples from patients who received aPD1. The algorithm extrapolated genomic mutational load (ML) from the panel. They concluded that ML determined by HC NGS stratified patients by response likelihood, and the approach might offer a widely available, clinically feasible predictor of response to aPD1.