New ASCP Education Examines TMB’s Effectiveness in Predicting Immunotherapy Response

Tumor Mutational Burden, or TMB, is emerging as the hot biomarker of the year. It measures the number of mutations in a tumor through genomic sequencing. And since some cancers have a higher frequency of mutations than others, identifying the number of mutations in a tumor may predict if a cancer patient will respond favorably to certain immunotherapies.

One of the challenges in implementing this biomarker, however, is that there currently are no standards for measuring the amount of mutations occurring in a tumor. Additionally, some healthcare professionals have been unsure of TMB’s clinical utility in predicting an immunotherapy response. However, on June 16, 2020, the FDA granted accelerated approval to pembrolizumab for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [>10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.

ASCP has just released an educational webcast, Immuno-Oncology Scientific Updates Webcast: Tumor Mutational Burden, to help pathologists and medical laboratory professionals stay current on all the latest developments surrounding TMB. The webcast, funded by an independent educational grant from Bristol-Myers Squibb, includes recommendations and general guidelines developed by the Friends of Cancer Research and Quality in Pathology (QuIP) that have been leading harmonization efforts and developing best practices around TMB, as well as updates from clinical trials on the clinical utility and how TMB may be used as a helpful biomarker.

“The challenge, from the pathologist’s and molecular laboratory perspective, has been: How does one validate and implement TMB when the practice has not been standardized?” explains Lauren Ritterhouse, MD, PhD, Assistant Professor at Harvard Medical School and Associate Director of the Center for Integrated Diagnostics in the Department of Pathology at Massachusetts General Hospital and faculty member for the webcast.

Until this past week’s FDA approval, TMB was an emerging biomarker used in the immunotherapy arena with regard to immune checkpoint inhibition. Now, it is becoming a new way to think about genetic mutation. Instead of looking at one mutation in one gene, it is looking at what the rate of mutation is across all genes. That is what the quantification is supposed to represent, Dr. Ritterhouse explains.

“Until recently, many laboratories have not been implementing this biomarker into their routine clinical practice,” she says. The hypothesis of why TMB would be a good predictive biomarker for immune checkpoint therapy is that a large number of mutations in the DNA will lead to a large number of changes at the protein level, which may be presented as “novel” proteins to the immune system, which may help the immune system generate an anti-tumor response. 

“Overall, TMB has transitioned from an emerging biomarker to one that will be increasingly used in clinical practice within FDA guidelines,” she continues. “ASCP has done a great job of following the development and emergence of this biomarker with a series of webinars to keep their members and audience up to date.”

Learn more about the new educational webcast on the ASCP web site at www.ascp.org/immuno-oncology.