Progressive melanoma in one Massachusetts hospital patient was completely neutralized with the help of so-called immune checkpoint inhibitors, writes Science author Jennifer Cousin-Frankel..
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These drugs prompt the immune system to seek out and destroy cancer cells, and in this case they worked perfectly, says Kerry Reynolds, an oncologist at the Massachusetts General Hospital (MGH) who helped care for the man..
But about a month after the infusion, when no melanoma cells were found in his body, the 64-year-old man was hospitalized in serious condition.. The drugs were putting too much stress on his immune system, damaging his colon and nervous system.. Doctors fought to save him for more than 3 weeks, but he died from severe intoxication.
Before he died, the man begged Reynolds to learn from his experience, and she promised she would.. Shortly thereafter, in 2017, Reynolds founded the Immunotherapy Severe Complications Service at MGH, where immunologist and genomist Alexandra-Chloe Villani conducted parallel research.
Together they aim to treat and study people with immune complications from these revolutionary cancer drugs.. By the way, Villani's mother was saved by checkpoint inhibitors, but as a result she developed arthritis..
About 10% of those who receive checkpoint inhibitors are hospitalized with immunotoxicity. About 1% die. A 2021 study found that, like Villani's mother, about 40% of those taking checkpoint drugs develop chronic complications, often arthritis or endocrine dysfunction..
“When people have 4 months to live, the risk is worth it,” says Reynolds. - For less advanced cancers, the risk profile changes.
Today, this drug-risk-benefit tension is particularly acute because, 11 years after the first checkpoint inhibitor was approved in the United States for the treatment of metastatic melanoma, they are saving people in the earlier stages of several types of cancer, including melanoma..
Over 40% of cancer patients in the United States are able to take medication and they are a 30 billion and growing market.
Complications superficially resemble known autoimmune diseases such as hepatitis or colitis, but develop suddenly. Some side effects become chronic but manageable.
In particular, adrenal or thyroid dysfunction, for example, can be controlled with once-daily medication..
Other complications are more devastating. For example, drugs can cause myocarditis, in which the immune system destroys the heart muscle.. Although much less common than many other immune complications, it is fatal in a quarter to half of cases..
Most patients with immune complications are currently on steroids.. But it's a crude tool and runs the risk of thwarting the cancer-targeting attack that checkpoint inhibitors are supposed to stimulate.. Therefore, researchers are looking for better countermeasures.
In Paris, Jean-Elie Salem, a Sorbonne cardiologist, was investigating an arthritis drug called abatacept, which suppresses T-cell activity, to treat myocarditis caused by checkpoints.. Researchers are still trying to determine if abatacept interferes with the benefits of checkpoint therapy, but in 2019, Salem and colleagues reported in the New England Journal of Medicine that a woman with lung cancer and myocarditis was successfully treated with an arthritis drug without tumor progression..
Shortly thereafter, Salem co-authored another paper describing the success of abatacept in a mouse model of checkpoint myocarditis (the senior author of this paper, published in Cancer Discovery, was James Ellison of Anderson Cancer Center, one of two Nobel Prize-winning scientists in.
Salem begins clinical trials of abatacept in more patients. Preliminary results give hope.
It was previously reported that for the treatment of certain types of cancer, T cells are reprogrammed by genetic engineering, focusing them on the recognition and destruction of cancer cells..