Over 144,000 Americans are expected to be diagnosed with melanoma this year.1 With a 15-20% 5-year survival rate for Stage IV patients, the future is not always optimistic.2 Thankfully, immunotherapy is changing that outlook. For example, one recent study found that an anti-PD-1 therapy doubled the survival rate in advanced melanoma cases.3
Still, immunotherapies may not work for everyone. Knowing who is likely to respond to immunotherapy will help ensure that these promising treatments deliver the most benefit. More informed treatment selection has the potential to steer patients away from ineffective medicines, which may reduce side effects and save both costs and disappointment. Tumor mutational burden (TMB) or mutational load is an emerging diagnostic measure that has been shown to help predict response to immunotherapy in certain cancers, including lung cancer, bladder cancer and melanoma.4, 5, 6
Foundation Medicine and our collaborators at Vanderbilt University have published new data supporting the use of TMB, as measured by our comprehensive genomic profiling assay FoundationOne®, to help predict response to anti-PD-1/PD-L1 treatment.7 These results add to the growing body of evidence that TMB may be useful for identifying patients most likely to benefit from immunotherapy and may bring us closer to our goal of impacting the greatest number of patients possible.
Previous research in melanoma has shown mutational load to be associated with clinical benefit from anti-CTLA-4 immunotherapy treatment.6 The current study sequenced melanoma samples from patients who had undergone anti-PD-1/PD-L1 treatment to determine whether TMB was correlated with that type of immunotherapy as well. Within both initial and validation cohorts (65 total patients), those who responded to treatment had higher mutational load compared to non-responders. In addition, objective response rate, progression-free survival and overall survival were superior in the high mutational load group as compared with intermediate and low mutational load groups.
Together, these data strengthen the predictive power of TMB for response to a range of existing immunotherapy options and helps to establish TMB as a clinically available tool to identify patients who are most likely to benefit from these powerful treatments.