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Comment & Response
April 11, 2019

Primary Resistance to Immune Checkpoint Inhibitors in Metastatic Colorectal Cancer—Beyond the Misdiagnosis

Author Affiliations
  • 1Department of Pathology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
  • 2Molecular Diagnostics Laboratory, InRASTES, NCSR Demokritos, Athens, Greece
  • 3Euromedica General Clinic, Thessaloniki, Greece
JAMA Oncol. 2019;5(5):740-741. doi:10.1001/jamaoncol.2019.0521

To the Editor Tumor DNA mismatch repair deficiency status is a determinant for response to immune checkpoint inhibitors (ICI) across cancer types1 and can aid in the identification of patients with Lynch syndrome. In a small cohort of patients with metastatic colorectal cancer (mCRC) who received ICI treatment, Cohen et al2 reported that 3 (60%) of 5 patients who did not respond to treatment had tumors mislabeled as defective mismatch repair (dMMR) in local laboratories. Cohen et al2 interpreted this finding as the major reason for ICI treatment failure and recommended routine double mismatch repair (MMR) testing with immunohistochemistry (IHC) and polymerase chain reaction (PCR)–based testing for microsatellite instability (MSI) and retesting tumors with discrepant IHC and/or PCR results (dMMR and microsatellite stable vs proficient MMR and MSI) in an expert central laboratory. Technical proficiency is undoubtedly an issue for predictive biomarkers but basing a practice-changing recommendation on such a small number of cases without any insight into the underlying biology of ICI failure seems excessive.

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