This retrospective study assessed the relationship between serious immune-related adverse events during anti-PD-1 cancer therapy and tumor mutational burden.

Study design

Investigators used the US Food and Drug Administration’s Adverse Events Reporting System to identify 47,304 adverse events related to the anti-PD 1 agents nivolumab and pembrolizumab.

The median tumor mutational burden in tumors was obtained from previously published comprehensive genomic profiling. Researchers estimated the reporting odds ratio (ROR) by comparing the odds of reporting adverse events while using anti-PD-1 with the odds for all other drugs in the database.

Outcomes

There was a significant positive correlation between the ROR of reporting an adverse event during anti-PD-1 therapy and the corresponding tumor mutational burden across multiple cancer types. The ROR of adverse events increased with a higher median number of coding somatic mutations per megabase of DNA (R = 0.704).

Limitations

This study used spontaneous reports as an indirect measure of risk of immune-related adverse events, which may have overestimated the results.

Clinical significance

Anti-PD-1 therapy has opened a new avenue in cancer treatment. Cancers with high tumor mutational burdens—such as melanoma and non-small cell lung cancer—correlate with higher risk of immune-related adverse events. Physicians should assess the risks versus benefits in each individualized case before treatment.

—Brian P. Marr, MD, Arpita Maniar, MS