# Dynamics of blood microsatellite instability (bMSI) burden predicts outcome of a patient treated with immune checkpoint inhibitors: a case report of hyperprogressive disease

## TL;DR

This case report shows that increasing blood microsatellite instability (bMSI) levels in a patient with colorectal cancer predicted poor response to immunotherapy.

## Contribution

The study introduces bMSI as a potential biomarker for monitoring treatment response in MSI-positive colorectal cancer patients.

## Key findings

- An increase in bMSI burden correlated with driver mutation burden and hyperprogressive disease in a patient treated with nivolumab.
- Serial liquid biopsy using NGS revealed dynamic changes in bMSI during immunotherapy.
- bMSI analysis may offer a timely method to assess treatment effectiveness in MSI-positive CRC patients.

## Abstract

Microsatellite instability (MSI) is a widely studied molecular signature, which is associated with long-term benefit in patients treated with immune checkpoint inhibitor therapy. This approach has been proven to be effective in the treatment of patients with MSI-positive colorectal cancer (CRC). Analysis of serial liquid biopsy samples allows to detect changes in the tumor in response to therapy. Typically, somatic mutations are used for tracing the dynamics of the tumor, and the assessment of DNA signatures such as MSI is not currently used for these purposes. Here, we describe a case of a MSI-positive CRC, who received nivolumab monotherapy. Sequential sampling of the patient’s plasma demonstrated an increase in MSI burden (bMSI), which was found to correlate with the increase of driver mutation burden one month after starting nivolumab, and hyperprogressive disease. Thus, analysis of bMSI in liquid biopsy via NGS may be a promising method for timely assessment of the treatment effectiveness received by patients with MSI-positive CRC.