Johns Hopkins Medicine Summary: In an expanded, three-year clinical trial of 86 patients with colorectal and 11 other kinds of cancer that have so-called 'mismatch repair' genetic defects, scientists have found that half of the patients respond to an immunotherapy drug called pembrolizumab Keytruda. Share: FULL STORY In an expanded, three-year clinical trial of 86 patients with colorectal and 11 other kinds of cancer that have is cancer genetic only 'mismatch repair' genetic defects, scientists at Johns Hopkins Medicine and its Bloomberg~Kimmel Institute for Cancer Immunotherapy have found that half of the patients respond to an immunotherapy drug called pembrolizumab Keytruda.
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In a report on the findings, which led the U. Food and Drug Administration to approve expanded use of pembrolizumab for patients, the researchers also say paraziții sunt curățați de corp found evidence that the immune responses closely aligned with mutations found in their cancers. The report is published online in the June 8 issue of the journal Science.
Mismatch repair MMR defects are part of a system that helps cells recognize and correct mistakes during DNA replication. For more than two decades, defective MMR genes have been linked to inherited and non-inherited or sporadic forms of colon cancer and used as biomarkers for diagnostic screening and chemotherapy treatment planning.
All tested positive for mismatch repair defects and had failed to respond to at least one prior therapy. They received pembrolizumab intravenously every two weeks for up to two years. Johns Hopkins biostatistician Hao Wang, Ph. After a median follow-up of Tumors completely disappeared in 18 of the In all, 66 of 86 77 percent had at least some degree of disease control, including those who had partial responses, meaning their cancers shrunk by at least 30 percent in diameter, and complete responses, meaning no radiologic evidence of the tumor.
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This also included those whose tumors did not grow, but remained stable. At one year after the start of therapy, 65 of the 86 patients 76 percent were alive, and 55 of the 86 64 percent were alive at two years. Three were treated additionally with surgery or radiation and continued treatment with pembrolizumab. All five remained alive at the time of the data cutoff.
Twenty-one of 40 patients with colorectal cancer 52 percent and 25 of 46 patients with cancers 54 percent in other organs, such as pancreas, ampullary, cholangiocarcinoma, gastric, endometrial, neuroendocrine, prostate, small intestine and unknown primary responded to the drug.
The most common side effects of the immunotherapy included fatigue, skin inflammation, joint pain and thyroid dysfunction.
At the time of the data cutoff of this report, 18 patients were taken off therapy after two years of treatment. Eleven patients have been off of immunotherapy for a median of 8. The remaining patients had some residual disease, were taken off therapy at two years some because of side effects and after an average of 7.
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The median point of survival without disease progression and overall survival has not yet been reached. However, the scientists estimate that disease-free survival at one and two years is 64 percent and 53 percent, respectively.
Without immunotherapy, patients with advanced, treatment-refractory cancers can expect to live less than six months.
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The researchers also performed is cancer genetic only on residual tumors in 20 patients. In 12, they found no cancer cells, only inflamed cells, fibrotic tissue and mucus. These patients were more likely to survive longer without progression of their cancer However, there was no difference in overall survival between these two groups.
Using gene sequencing and methods to stimulate T-cells, immunologists, led by co-author Kellie Smith, Ph. In three patients, they found these cells rapidly increased in the circulating blood after immunotherapy was administered, peaking at one to two months later, often prior to detecting tumor regression via CT scans.
The mutations disable cells' ability to repair errors in the DNA replication process, which triggers unchecked cellular growth, a hallmark of cancer. Two decades later, an idea for the current clinical trial took root when Johns Hopkins experts discovered mismatch repair defects in a single patient with colon cancer who responded to immunotherapy while other patients with colon cancer did not.
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To estimate how many patients with cancer may be candidates for pembrolizumab based on their mismatch repair defects, the scientists sequenced genes in 12, patients with 32 different tumor types. They estimate that mismatch repair defects occur in nearly 5 percent of patients with 11 types of cancer, including the endometrium, stomach, small intestine, colon and rectum, cervix, prostate, bile duct, liver, neuroendocrine system, non-epithelial ovary and uterine sarcomas.
Flaws in a tumor's genetic mending kit drive treatment response to immunotherapy -- ScienceDaily
Note: Content may be edited for style and length. Journal Reference: Dung T. Le et al. Mismatch-repair deficiency predicts response of solid tumors to PD-1 blockade.