MSI-High and dMMR mCRC: Immunotherapy's Growing First-Line Role

In “Immunotherapy in MSI-High and dMMR mCRC,” Dr. Strickler discusses how immune checkpoint inhibition has reshaped treatment for patients with MSI-high or deficient mismatch repair metastatic colorectal cancer. Dr. Strickler describes MSI-high and dMMR disease as biologically distinct from other forms of metastatic colorectal cancer and explains why it is managed differently. He reviews the impact of KEYNOTE-177, which established pembrolizumab as a first-line immunotherapy option, and discusses how CheckMate-8HW further expanded the landscape with combined CTLA-4 and PD-1 inhibition.

The conversation emphasizes that immunotherapy selection remains individualized. Age, comorbidities, performance status, and patient goals all factor into the decision between available immune-based approaches. Dr. Strickler also discusses the potential for prolonged disease control in many patients and the smaller group who develop primary or late resistance.

When progression occurs, the pattern of disease becomes important. A solitary progressing lesion may be approached differently from widespread systemic progression, and tumor heterogeneity may help explain why some disease sites escape immune control. In selected situations, additional immune-based strategies may be considered, although these approaches are not necessarily standard. The episode reinforces the importance of identifying MSI-high and dMMR disease early so that appropriate immunotherapy options can be incorporated into first-line treatment.

Our next episode, “Defining Treatment Failure and Selecting Second-Line Therapy in mCRC,” explores how clinicians recognize when first-line treatment is no longer providing adequate benefit and determine the next treatment approach.