TMB threshold For Keytruda

[meatie]

Anyone know what the tumor mutation burden (TMB) threshold is for Keytruda to be possibly successful?

[juliej]

I don't know the specific number for CRC right now, but the field of oncology is going through changes with respect to TMB as a predictive marker. They are working on specific cutoffs for each tumor type since the success of TMB as a marker varies by histology. The only number I've heard for Keytruda is 10 or more mut/Mb. That used to be the "high" status number, but like I said things are evolving.

For example, a recent article in the Journal of Clinical Oncology showed that patients were most likely to respond to Keytruda if they had both high TMB and high levels of inflammation (measured by PD-L1 status). Right now they're thinking predictive models should combine PD-L1, TMB, tumor, and immune markers (MSS status, for example) to get a more accurate response prediction.

There are also some issues involving the way various labs calculate TMB. Originally, Foundation just reported the data quantitatively, not according to its potential value for immunotherapy success (qualitatively). Now it's changed its process to include whether patients have high/medium/low TMB status, based on cutoffs for specific cancer types. Foundation and MSK are both involved in an effort to standardize the way TMB is calculated and reported so things should improve very soon.

Hope this helps.
Juliej