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Research: Immunotherapy can help fight aggressive brain tumors



Patients with the aggressive glioblastoma brain tumor lived longer if treated with immunotherapy before surgery.

In a small online study, patients lived almost twice as long as the average expectation for patients with glioblastoma when given the drug that slows down the immune system. Previous research has focused on post-operative drug delivery

"This is an important first step in supporting patients with immunotherapy," said Robert Prins, lead author of the study and a tumor immunologist at UCLA, who studied the multi- institutional randomized study.

Some patients were enrolled in the MD Anderson Cancer Center, home of Allison, who received a Nobel Prize last fall when he tracked down the first brakes of the immune system and made persistent attempts to turn the results into cancer treatment. The known as checkpoint inhibitors drugs have led to a cure of patients with particularly deadly forms of disease such as lung cancer and melanoma.

Some patients were enrolled in the MD Anderson Cancer Center, home of Allison. who received a Nobel Prize last fall when he tracked down the first brake on the immune system and made a stubborn effort to turn the finding into cancer treatment. The medicines known as checkpoint inhibitors have been found to heal in a subset of patients with particularly lethal forms of the disease, such as lung cancer and melanoma. Former President Jimmy Carter is her best-known beneficiary.

But treatment, including the drugs used in combination, had been reported in patients with glioblastoma, the cancer that included Delaware Attorney General Beau Biden, US Senator John McCain, and John Mendelsohn, former President of MD Anderson,

, On average, the disease kills most patients about 1

1/2 years after diagnosis and six to nine months after onset following initial treatment, typically surgery, then chemotherapy and radiation

The results of the new study are significant There have been few new treatments for glioblastoma in the past two decades. The previous failure of checkpoint inhibitors was considered a big disappointment.

"It made me feel that immunotherapy, like everything else, would not work for brain cancer," Dr. Frederick Lang, neurosurgeon at MD Anderson's innovative immunotherapy research with glioblastoma, was not involved in the new study. "That's why this study is so exciting – it gives great optimism that immunotherapy can be effective if we use it properly."

The study published in Nature Medicine was not designed to test the new strategy. Results are improved so that they learn what happens to a brain tumor when a checkpoint inhibitor is given. This is a little easier to investigate if the drug is administered prior to surgery, as tumor samples can then be screened after surgery. There are no such samples that could be studied if the drug is given after surgery.

The study evaluated 35 patients with recurrent glioblastoma, 16 of whom received the checkpoint inhibitor Keytruda before and after surgery and 19 only after surgery. Not only did the study show a strong immune response in samples from tumors removed by those who received the drug prior to surgery, but also that these patients lived an average of 417 days more. Patients who received the drug after surgery lived an average of 228 days.

Prins said that some patients who received the drug before the operation are still alive, now about two years after the disease.

I think every one of us expected that, "Dr. John de Groot, a MD Anderson neuro-oncologist who led the Houston part of the study. "These results must be validated with additional studies. However, this is very important as the three-week treatment before surgery has an impact on survival. As a result, we re-examine how we treat these patients.

De Groot said that the results of the study are unlikely due to chance, as patients were enrolled in a number of facilities (seven in all) and have a smaller, nonrandomized study. The MD Anderson study showed similar findings Results. Some details of this study were presented at two cancer conferences, but have not yet been published.

The MD Anderson sent 15 patients to the treatment arm. The average survival time after preoperative treatment with Keytruda exceeded one year and two of the patients lived for 34 months.

Keytruda targets a brake known as PD-1; Yervoy, the drug developed by Allison, targets a brake known as CTLA-4.

Follow-up plans call for the combination of Keytruda and Yervoy; therapeutic vaccines that boost the immune system; and the latest, most radical immunotherapy, the injection of viruses that stimulate the immune system. Such oncolytic virus therapy is an immunotherapy that has previously been promising in brain tumors, including the benefit of a patient who has been 12 years old since treatment, but research is still at an early stage.

Dr. David Baskin, a neurosurgeon at the Houston Methodist Hospital, whose research on oncolytic virus therapy with the 12-year-old survivor had the greatest success, said he was seriously considering adding preoperative checkpoint inhibitors to his work, but would like to wait, as the study said was small and was needed for review. But he called it "very important" and said, "It will give us important clues as to how to combine the immune response that surgery provides with these drugs to improve survival – and can help us with many other cancers elsewhere Body help. "

MD Andersons Lang is already researching glioblastoma patients who make a combination of viral oncolytic virus therapy and Keyruda.

Researchers are not yet sure why using Keytruda before surgery was so much better than afterwards. However, they believe that the drug elicited a systemic immune response that was previously suppressed by the tumor and that subsequent surgery removed the immunosuppressive environment along with the tumor. On the other hand, if the checkpoint inhibitor is administered after surgery, immune cells can no longer be released because the tumor has been removed.

Prins states that the biological information gathered from the tumor specimens should also lead to a better understanding of the mechanisms by which some patients produce strong immune responses to therapy, while others do not.

The study was funded by a number of groups, including the National Institutes of Health and the Parker Institute for Cancer Immunotherapy, the organization that was launched in 2016 with a $ 250 million donation from Napster. Co-founder Sean Parker.

todd.ackerman@chron.com


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