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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 Surgery, Shanghai Baoshan District Combining Traditional Chinese and Western Medicine Hospital, Shanghai, China
  • 2Division of Colorectal Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, PR China
JAMA Oncol. 2019;5(5):739-740. doi:10.1001/jamaoncol.2019.0518

To the Editor Cohen et al1 investigated possible mechanisms underlying primary resistance to immune checkpoint inhibitors (ICI) in metastatic colorectal cancer (mCRC) displaying microsatellite instability (MSI) or defective mismatch repair (dMMR). Among 38 patients in the study with mCRC displaying MSI or dMMR, primary resistance to ICI was observed in 5 individuals (13%), of which 3 (60%) were misdiagnosed (as microsatellite stable or displayed proficient mismatch repair). Multicenter reassessments of the accuracy of MSI and dMMR status in 93 cases of mCRC revealed a misdiagnosis rate by local assessment of 10%. The authors concluded that primary resistance of mCRC tumors displaying MSI or dMMR to ICI was mainly due to misdiagnosis of the MSI/dMMR status and thus recommended routinely using both immunohistochemistry and polymerase chain reaction tests to confirm the status prior to ICI treatment. We thank the authors for their important contributions, and this article explained one possible reason for primary resistance to ICI in mCRC displaying MSI or dMMR. However, beyond the misdiagnosis of the MSI/dMMR status, we would like to offer additional remarks concerning other explanations for primary resistance to ICI in mCRC.

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