Over the past few years, the US FDA has approved 6 checkpoint inhibitors and 2 CAR T cell therapies, helping drive interest in immunotherapy research. However, the approved therapies are not without their limitations, as over 50% of patients treated with checkpoint inhibitor therapies do not respond to treatment or have extremely adverse reactions to immunotherapy. Clinical labs are working to set up tests that help identify the type of tests that patients require and assist in monitoring their responses to treatment.

After the FDA approved the pembrolizumab checkpoint inhibitor in 2017, testing for microsatellite instability (MSI) and mismatch repair (MMR) in tumors has become a key point of interest for researchers; however, there are no FDA-approved assays to measure and evaluate MSI. Certain labs measure MSI through NGS by analyzing varying areas of the genome to search for different tumors; however, most labs use PCR-based kits that analyze only five targeted genomic markers for colorectal and endometrial cancers. This can create challenges for clinicians when they need to test MSI in a different type of tumor.

Because of this, as well as the higher cost for MSI testing, most labs begin with MMR testing. If any markers are determined as missing in the MMR test, then the problem is an MMR defect and MSI testing is not required, although some labs still perform both tests due to MSI testing being traditionally used for colon and endometrial cancers. Tumor mutational burden (TMB) may also be a potential tool to predict checkpoint inhibitor response in patients, but testing for TMB is costly and time consuming, such that few national labs conduct these tests.

Clinical lab directors look to work with clinical trial data to determine the importance of the test for the patient, as well as the technology required to perform the test, lab logistics, and the cost of the test and reimbursement options.

Source: AACC