David Rimm, MD
“TUMOR MUTATIONAL burden is an emerging biomarker independent of programmed cell death ligand 1 (PD-L1) level. There are a few reasons for enthusiasm. Tumor mutational burden is a compelling biomarker for response and progression-free survival. Six-month progression-free survival is 50% with a high tumor mutational burden vs 31% with a low tumor mutational burden. This is really a new biomarker, and it is complementary with respect to PD-L1,” said formal discussant David Rimm, MD, PhD, a pathologist at Yale University School of Medicine, New Haven, Connecticut.
Cause for Concern and Challenges Ahead
DR. RIMM listed some questions that may be cause for concern:
- How reproducible are these findings? How do assays from different vendors compare?
- Does tumor mutational burden require a large tissue sample?
- What about the 9% discordant rate shown in two analyses?
- Will the cut point of tumor mutational burden >10 mut/mb hold up?
Dr. Rimm said the progression-free survival data looked good, but we need to await the overall survival data. “There is the possibility that high mutational burden tumors will evolve and become resistant,” he told listeners. “The biggest challenge is the lack of standardized testing. Tests have to be standardized to move the field forward. A cut point of 10 mut/mb in one assay is not the same as a cut point of 10 mut/mb in another assay.”
He continued, “The elephant in the room is the cost of testing for tumor mutational burden. It costs about ten times as much as immunohistochemistry.”
Dr. Rimm concluded, “These results are provocative. Tumor mutational burden warrants further study and standardization of testing before we use it in the clinic. In my view, tumor mutational burden is not yet ready for prime time.” ■
DISCLOSURE: Dr. Rimm reported no conflicts of interest.
