New therapy shows promise for melanoma metastasized to the brain

October 1, 2018 | by Maxine Nunes

Kim Margolin, M.D. Kim Margolin, M.D.
A noteworthy new study, published last week in the New England Journal of Medicine and featured in the New York Times, brings new hope to people with melanoma that has metastasized to the brain.
Until now, the statistics for these patients told a grim story. When treated with the standard arsenal of stereotactic radiation or surgery, fewer than 20 percent survived a year. But in the 14 months since this trial closed, 80 percent of the trial participants are still alive.
Groundwork for the study began five years ago under the direction of Kim Margolin, M.D., now a medical oncologist at City of Hope and an internationally recognized expert in melanoma. She initiated the study, co-developed it with Bristol-Myers Squibb, then became the co-principal investigator and co-author of the NEJM paper.
I have a passion for treating brain metastases of this disease, and it’s just wonderful to see the culmination of this work,” she said.
Patients in the trial were given a combination of two drugs, ipilimumab and nivolumab. Both are immune checkpoint inhibitors, a type of immunotherapy that unleashes the suppressed power of T cells so that they can destroy cancer.
Though oncologists now prescribe both drugs for some cases of melanoma metastasized to other parts of the body, this is the first time their combined effect in patients with brain metastases has been studied.
Finding an immunotherapy that works in the brain, even against diseases that respond to immunotherapy when they involve locations outside of the brain, has been particularly challenging because these immunotherapy drugs do not penetrate the intact blood-brain barrier. Now we know that ipilimumab and nivolumab, when given intravenously, can activate T lymphocytes to recognize and kill tumor cells — and these T cells are capable of entering the brain due to their motility and flexibility.
This trial involved metastatic melanoma to the brain that was asymptomatic, and the treatment is likely to become one of the best standards of treatment for these patients. The next step will be a trial with those who do have symptoms or need steroids, which can suppress that critical T cell immune response.
As principal investigator of the City of Hope trial, Margolin has seen, in a personal way, the new lease on life it has given to people who had, in effect, been under a death sentence. She was particularly moved by one of them, a middle-aged man with melanoma and tumors in his brain.
One year after the trial ended, he was able to return to the two things in life he cared about most, helping his elderly mother and hiking the San Gabriel Mountains,” she said. “And to celebrate his new lease on life he also bought himself a brand new truck.”
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