Understanding the Core Scientific Considerations in IO Diagnostics and Treatment

Rapid advances in immuno-oncology (IO) have dramatically increased the number of patients who are eligible for IO testing. IO is such a new frontier that the oncology community is latching onto the fact that IO drugs have shown great promise and cure. They are trying to do every diagnostic test under the sun, even if they have yet to understand their uses.

The timing is right for pathologists to step up and guide the appropriate use of IO agents and shape treatment decisions. Yet they, too, must enhance their knowledge about IO testing.   

ASCP’s innovative IO education strategy is designed to increase the IO‒related knowledge, skills, and competence of pathologists and laboratory professionals involved in cancer diagnosis and treatment. It also supports the implementation and dissemination of best practices in IO testing, treatment options, and communication in multidisciplinary teams to improve quality of care.

“Pathologists and laboratory professionals need to become more familiar, for example, with the nuances between microsatellite instability/mismatch repair testing (MSI/MMR),” says Robert Anders, MD, PhD, Chair of ASCP’s IO Work Group. “Often, MSI and MMR tests are used interchangeably, but they are not identical. There are subtle differences in the interpretation of the two. Pathologists and laboratory professionals need to be able to articulate these differences to their oncology peers and competently administer these tests.” 

Dr. Anders is Associate Professor of Pathology and Co-Director of the Tumor Microenvironment Lab at the Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, who has been working with checkpoint inhibitors for over a decade. He and his colleague, Feriyl Bhaijee, MD, explain MSI and MMR testing in detail in ASCP’s online IO course, “Understanding the Importance of Mismatch Repair Deficiency and Microsatellite Instability in Pathology.”¹

Another challenge is the interpretation of PD-L1 testing. A patient’s biopsy or resection sample will be stained for PD-L1. Based up on whether the patient expresses PD-L1 or not may determine whether they are eligible for IO therapy.

“What we didn’t anticipate is that PD-L1 interpretation differs between organ types,” explains Dr. Anders. “For example, gastric cancer is interpreted differently than melanoma. So, our challenge here is having the laboratory ready to administer and interpret these stains because the protocols to do the staining may differ by organ.”

“For the pathologists or the person interpreting the test results, the interpretation changes by organ,” he continues. “This is something that is not common in immunohistochemistry testing. ASCP has education modules that explain how these interpretations are done.”

Dr. Anders anticipates that another challenge that may arise in the future involves DNA testing for mutations, as well as MSI status—the biomarkers that drive clinical care. It’s just as important to know the KRAS, EGFR and MSI status of a patient in order to deliver therapy.

“The treatment algorithms also depend on the mutational status of particular genes, as well as MSI/MMR status,” he says. “The challenge is to get all of this testing done in one process. It is unclear what is the best way to accomplish this.”

In early spring 2019, ASCP plans to unveil an online education module to educate and enhance awareness about the total mutational burden (TMB), mutational status and MSI status.

Currently, predictive biomarkers are the emphasis, synonymous with personalized medicine. Dr. Anders paints a future where “the more biomarkers we look into, the more individualized the therapy will become. And almost all of this testing is done in tissue, which is the domain of pathologists and molecular diagnostics.”

Resources

1. ASCP’s online IO course, “Understanding the Importance of Mismatch Repair Deficiency and Microsatellite Instability in Pathology,” is available at https://www.ascp.org/content/learning/immuno-oncology.