Inflammation and mutational burden differentially associated with nivolumab or ipilimumab combination efficacy in colorectal cancer.

The phase 2 CheckMate 142 study demonstrated durable clinical benefit of nivolumab alone and combined with ipilimumab in previously treated microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer.

Exploratory biomarker analyses revealed:

• Higher inflammation-related gene expression correlated with better response and survival with nivolumab monotherapy.
• Higher tumor mutational burden, tumor indel burden, and degrees of microsatellite instability were linked to improved outcomes with the combination therapy.

These findings suggest:

• Tumor antigenicity may drive the efficacy of the combination therapy.
• Baseline tumor inflammation influences response to monotherapy.

Further validation in larger, randomized trials is needed.