A Test to Ease the Burden of Selecting Patients for Immunotherapy.

As the field of immuno-oncology matures, the ability to identify patients who are likely to respond to its therapies is coming to the center. Some patients achieve complete responses, whereas, in others, the disease stubbornly progresses. One of the patient stratification biomarkers that has been well studied is PD-L1 expression, using an immunohistochemistry (IHC)2 assay with U.S. Food and Drug Administration (FDA)-approved kits. A challenge with PD-L1 levels is that some patients with low PD-L1 expression still show strong response. Also, the assays suffer from a level of subjectivity that is inherent in the technology and a lack of standardization (1). An alternative marker that is gaining traction is tumor mutational burden (TMB).Checkpoint inhibitors work by releasing the brakes on the immune system, allowing immune cells to target and destroy a tumor. The belief is that the immune cells recognize nonself aspects of tumors such as neoantigens that are caused by somatic mutations. Thus, looking for tumors with genomic instability and a high mutational burden makes sense.The journal spoke with Foundation Medicine, whose FoundationOne CDxTM test (F1CDx) recently became the first FDA-approved platform with analytic claims for TMB. The test reports genetic mutations in 324 genes and TMB, as well as its cousin, microsatellite instability. The report can provide insight for clinicians on FDA-approved therapies that could apply to a patient.One way to measure TMB is through whole exome sequencing (WES), an approach not currently practical as …