A new study showed a greater incidence of immune-related adverse events (irAEs) in patients with higher tumor mutation burden (TMB) treated with immune checkpoint inhibitors (ICIs) for metastatic urothelial cancer. Study findings were presented at the American Society of Clinical Oncology 2021 Genitourinary Cancers Symposium.

Patients with metastatic urothelial cancer in this study were treated with ICI as a monotherapy or in combination. Tumor sequencing data for each patient were used to calculate TMB, and the threshold for TMB was 10 mutations/megabase (Mb). The study investigators explored associations between TMB and irAEs.

A total of 101 patients were included in the analysis, with 32% reporting irAEs. The median TMB was 15.4 mutations/Mb in patients with irAEs, whereas it was 9.8 mutations/Mb for those without irAEs, which was a significant difference. No significant association was seen for TMB and irAE grade, however.

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There were 26 responders, 68 nonresponders, and 7 patients without response data. The response rate was highest (56%) in patients with both irAEs and high TMB. Patients who had irAEs and low TMB had a response rate of 28.6%, and patients who had no irAEs with high TMB had a response rate of 21.2%. The response rate was lowest (10.3%) among those who had no irAEs and low TMB. The overall comparison of these response rates showed significance (P =.002 for Chi-square test).

The study investigators concluded that TMB was linked to a higher incidence of irAEs in this study population and that the combination of high TMB with irAEs was associated with the most favorable response rates.

Disclosure: Some authors declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original abstract for a full list of disclosures.


Akl EW, Nuzzo PV, Adib E, et al. Association between tumor mutational burden (TMB) and immune-related adverse events (irAEs) in patients (pts) with metastatic urothelial carcinoma (mUC) during checkpoint immunotherapy. J Clin Oncol. 2021;39(suppl 6):abstr 489. doi:10.1200/JCO.2021.39.6_suppl.489

This article originally appeared on Oncology Nurse Advisor