According to a recent study, immunotherapy may be beneficial for thousands more people than those who are already receiving it for colorectal and endometrial cancer diagnoses. Researchers demonstrated how crucial it is to use DNA Mismatch Repair Deficiency (MMR-D) as a guiding diagnostic when choosing immune checkpoint inhibitors (ICIs) for therapy. MMR-D is the most frequent cause of hereditary endometrial cancer and is linked to an elevated risk of acquiring many cancer types.
The study, which was published on December 28 in Cancer Cell, compared two laboratory testing approaches for cancer diagnosis: next-generation sequencing (NGS), a new technology for DNA sequencing that can identify specific patterns of mutations, and traditional immunohistochemistry (IHC), a lab technique that uses antibodies to detect antigens in tissues. The researchers discovered that NGS offers a more accurate assessment of MMR status.
We found that 1% of patients with colorectal cancer and 6% of patients with endometrial cancer are functionally mismatch repair-deficient but are still missed by IHC, the current standard of care testing. However, these cancers are detected by NGS. Importantly, we showed that these patients (missed by IHC and detected by NGS) achieved long-term benefit from immunotherapy. We recommend revisiting guidelines for mismatch repair testing to include both this NGS and IHC.”
Amin Nassar, MD, senior author of the study and member of Yale Cancer Center
According to research, combining NGS and IHC might find an extra 6,000 patients in the US each year who might benefit from immunotherapy that extends life. If IHC was the only method employed, these individuals would not be provided immunotherapy.
In order to confirm these results in individuals with colorectal and endometrial malignancies and investigate the use of NGS in other cancer types, the researchers urge bigger investigations.
The majority of the study was completed by Nassar, a clinical fellow at Yale Cancer Center, while he was a resident at Brigham and Women’s Hospital. Elias Bou Farhat, MD, the first author from Brigham and Women’s Hospital, joined him.
Bou Farhat, E., et al. (2023). Benchmarking mismatch repair testing for patients with cancer receiving immunotherapy. Cancer Cell. doi.org/10.1016/j.ccell.2023.12.001.