Tumor Mutational Load Predicts Survival Post-Immunotherapy

However, the immune system is complicated, and it has proved difficult to determine what makes one tumor vulnerable to treatment but allows another to escape unscathed.

A large team of scientists working with the Memorial Sloan Kettering Cancer Center (New York, NY, USA) analyzed DNA sequence data for advanced cancers from more than 1,600 people who had been treated with immunotherapies called checkpoint inhibitors (ICI). The team also analyzed the sequences of advanced cancers from more than 5,300 people who had not been treated with checkpoint inhibitors. The study looked at ten different kinds of cancer, including melanoma and breast cancer. Findings in selected cancer types suggest that tumor mutational burden (TMB) may predict clinical response to ICI.

In most of those cancers, the team found that a higher number of mutations were associated with a better chance of responding to checkpoint inhibitors. This finding matches the results of other preliminary studies reported in recent years. The current study was the first to find improved survival in such a wide range of cancers, and in a population of people, who had received a variety of previous treatments. The data also showed that the number of mutations that predicted a good response to immunotherapy varied from one type of cancer to another.

The authors noted that survival results may have been affected by participants who switched from the control group to the immunotherapy arm of the trial. Checkpoint inhibitors were more likely to halt tumor growth in those with a higher number of mutations than in those with fewer mutations, even if there was no demonstrated difference in a person's survival rate. The study was published on January 14, 2019, in the journal Nature Genetics.

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Memorial Sloan Kettering Cancer Center