In the March 8 issue of the New England Journal of Medicine, a team of researchers at Memorial Sloan Kettering Cancer Center report on an extremely rare phenomenon known as the abscopal effect, in cancer patients with melanoma, treated with the immunotherapeutic agent ipilimumab (Yervoy™). The study was conducted at Memorial Sloan Kettering’s Ludwig Center for Cancer Immunotherapy.
The abscopal effect occurs when localized radiation therapy delivered to a single tumor in a patient with advanced stage cancer destroys tumors outside of the radiation field. Even though this phenomenon is extremely rare, it has been reported in several cancers, including kidney, melanoma, and lymphoma cancer.
The findings of the unique single-patient study could help researchers better understand the role the immune system plays in fighting cancer. According to the researchers, the combination of radiation therapy and ipilimumab may be a promising method for the treatment of melanoma.
Jedd Wolchok, M.D., Ph.D., a medical oncologist at Memorial Sloan Kettering Cancer Center, with a joint appointment in the Sloan Kettering Institute’s Immunology Program, and senior author of the study, explained:
“We are excited about these results, and what we have seen in this one patient proves the principle that adding radiation therapy to immunotherapy may be a promising combination approach to treatment for advanced cancer. What we think is happening here is that the immune system’s cancer-fighting response is turned up a notch with the addition of focused radiation.”
In this study, the patient with advanced stage melanoma was treated with an immunotherapy called ipilimumab, recently approved by the US Food and Drug Administration. Over time, the patient’s cancer slowly metastasized to an area near the spine, as well as in the lymph nodes and spleen. In order to help with pain relief, the patient received localized radiation therapy to the melanoma tumor located near the spine.
The researchers discovered that the targeted tumor significantly decreased in size after the radiation treatment, and that the tumors in the patients spleen and lymph nodes also benefited, even though they were not directly targeted by the radiation treatment, consistent with the abscopal effect. More than one year after undergoing radiation therapy the patient continues to do well.
Researchers are unsure about how the abscopal effect works to destroy cancer in individuals. According to prior studies in mice, the abscopal effect may rely upon activation of the immune system.
In this study, the researchers measured alterations in the patient’s immune system over the course of treatment. At the time of abscopal effect, the researchers saw changes in tumor-directed antibody levels and immune cell populations. Results from the study support the theory that radiation may help trigger the immune system to fight cancer.
Ipilimumab is an immunotherapy that uses the body’s own immune system in order to fight cancer. The drug, which blocks a target called CTLA-4, was approved by the FDA in March 2011. Ipilimumab is the first ever medication to demonstrate an improvement in overall survival for individuals suffering with advanced melanoma. Ipilimumab was developed by James Allison, Ph.D., Chair of the Sloan Kettering Institute’s Immunology Program.
This study provides better understanding into how radiation may help trigger the immune system to attack cancer and indicates innovative therapeutic avenues to explore. Human trials are currently in progress, in order to confirm the method of combining ipilimumab with radiation therapy, for the treatment of melanoma and prostate cancer.
The study was funded by the National Institutes of Health, the American Cancer Society, the Melanoma Research Alliance, Swim Across America, the Cancer Research Institute, the Virginia and D. K. Ludwig Fund for Cancer Research, the Lita Annenberg Hazen Foundation, and the Commonwealth Foundation for Cancer Research.
Written by Grace Rattue