Allison Shelley

May 30, 2015


CHICAGO — The first genomic indicator of response to immunotherapy has been identified, reporters heard here at the American Society of Clinical Oncology meeting. A new study shows that a mismatch repair (MMR) deficiency can predict response to pembrolizumab (Keytruda, Merck) in colorectal and other cancers.

"This study is really about bridging immunotherapy and genomics for the benefit of patients, and it has implications for a broad range of cancers," said Dung Le, MD, from the Johns Hopkins Kimmel Cancer Center in Baltimore.

Problems with mismatch repair lead to an accumulation of genetic mutations in a tumor. "When you have a tumor that has thousands of mutations, this increases the probability that the immune system can recognize and destroy the tumor," Dr Le explained. "We suspected that immune checkpoint inhibitors such as pembrolizumab would work particularly well against MMR-deficient tumors."

Mismatch repair deficiency is found in about 20% of noninherited colorectal cancers and in other tumor types, including stomach, small bowel, endometrial, prostate, and ovarian cancer.

In this study, there were substantially more mutations in MMR-deficient tumors than in MMR-proficient tumors (1782 vs 73). And more mutations were linked to better response to pembrolizumab.

To learn more about mismatch repair and this study by Dr Le's team, read Medscape Oncology's news report.


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