The previous posts of this blog series have addressed the why and how of the Tumor Mutational Burden (TMB) Harmonization Project. What has not yet been addressed are the results of the project impact patient care. Phase III of the project sought to address the clinical validation of TMB as a predictive biomarker to help distinguish which patients would likely benefit from immunotherapies. The TMB Harmonization Consortium, which was led by Friends, conducted an unbiased analysis that looked at published studies where TMB had been assessed in patients with different tumor types who were treated with immunotherapies, as well as a wealth of data from ongoing clinical trials. From the reviewed data, the Consortium agreed and suggested to the scientific community that a TMB measurement of 10 mut/Mb (mutations per megabase or the unit used to report TMB) was a reasonable benchmark to determine if a patient is likely to respond to immunotherapies despite the location of where their tumor originated.
“Participating in the FOCR TMB Working Group has been a fantastic collaborative undertaking. I have not previously experienced this level of collaboration by diagnostic companies, academia, pharma and other industry, as well as FDA – all towards the standardization of this important biomarker for immuno-oncology!” – Dr. Gary A. Pestano, Chief Development Officer, NYS CLEP Laboratory Director, Biodesix
This recommendation guided a recent approval of an immunotherapy in the tissue-agnostic setting (meaning the indication for the use of the drug is not tied to a single tumor site). This provides a treatment alternative to those who seem to have run out of other treatment options, including patients with rare tumors that do not have tumor-specific clinical trials or immunotherapies available to them. Tissue-agnostic biomarkers define tumors by their molecular alterations rather than the site of the tumor. This is quite a paradigm-shifting approach to clinical care, and it highlights the power of precision oncology. However, more research is needed to understand the optimal TMB level for treating specific tumor types. This tissue-agnostic approval is a step in the right direction and a great starting point to ensure therapy access for patients with no other options.
This is the final post of the TMB Blog Series in the lead up to the presentation of the TMB Harmonization Project data on July 14 and 23. You may register for the event on the 14th here. Thank you for following along and be sure to watch out for more TMB-related posts including the event summary that will be posted here on the blog as well!