Thursday, March 8, 2012
Findings from a multidisciplinary research team led by Memorial Sloan Kettering medical oncologist and immunologist Jedd Wolchok could help shed light on the immune system’s role in fighting cancer.
Researchers at Memorial Sloan Kettering have reported a rarely seen phenomenon in cancer patients: Metastatic melanoma tumors disappeared throughout the body after a patient received radiation focused on one tumor.
The patient had radiation therapy after treatment with ipilimumab (trade name YervoyTM), a type of immunotherapy that harnesses the body’s own immune system to attack cancer. The phenomenon, known as the abscopal effect, occurs when localized radiation therapy to a single tumor in patients with advanced disease results in tumor disappearance outside of the irradiated area. Though the abscopal effect is extremely rare, it has been described in several cancers including melanoma, lymphoma, and kidney cancer.
Findings from a multidisciplinary research team led by Memorial Sloan Kettering medical oncologist and immunologist Jedd Wolchok are published in the March 8 edition of the New England Journal of Medicine. This unique single-patient study could help shed light on the immune system’s role in fighting cancer.
“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,” explains senior author Dr. Wolchok, while noting that this patient’s response to the radiation treatment might be unusual. The researchers cannot tell whether other patients receiving ipilimumab might benefit from radiation therapy until studies have been conducted in more patients.
Focusing Radiation Therapy on One Tumor
Dr. Wolchok and colleagues treated a patient with advanced melanoma whose disease had spread from a mole on her back to other parts of the body. The patient was enrolled in a clinical trial and received ipilimumab, which was approved by the US Food and Drug Administration in March 2011, as part of her treatment. The drug did not initially prevent the disease from worsening over time, with metastatic tumors growing in the spleen, lymph nodes, and an area near the spine.
As her disease progressed, the patient received localized radiation therapy to the tumor near the spine to help with pain relief. The radiation caused the tumor near the patient’s spine to shrink significantly.
Unexpectedly, the tumors growing in the patient’s spleen and lymph nodes also shrunk, even though they were not directly targeted by the radiation therapy, which is consistent with the abscopal effect. The patient continues to do well more than one year after radiation therapy.
“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,” Dr. Wolchok says.
Another Success for Immunotherapy
Ipilimumab is the first drug ever shown to improve overall survival for patients with advanced melanoma. The therapy, which targets a protein called CTLA-4, was developed by James P. Allison, Chair of the Sloan Kettering Institute’s Immunology Program.
For more than 20 years, Dr. Allison’s research has focused on the mechanisms by which immune cells called T cells mediate the body’s defense against infections and cancer, with an emphasis on how T cell responses might be manipulated therapeutically to attack tumors. Dr. Wolchok was the principal investigator in a pivotal phase III study of ipilimumab in patients with metastatic melanoma.
Scientists are not certain how the abscopal effect works to eliminate cancer in patients. Studies in mice suggest that the effect may depend upon activation of the immune system. In this case study, changes in the patient’s immune system were measured over the course of treatment. At the time the abscopal effect occurred, the team observed changes in the patient’s immune system. Their findings support the idea that radiation may help stimulate the immune system to fight cancer.
This patient’s dramatic response provides new insight into how radiation may help activate the immune system to fight cancer, encouraging investigation of novel therapeutic strategies. Clinical trials to explore the approach of combining radiation therapy with ipilimumab for the treatment of melanoma are expected to begin soon at Memorial Sloan Kettering Cancer Center.
In a March 7 interview with NBC News, Dr. Wolchok explains, “We’re very excited about this result because we treated just one tumor with radiation therapy in this patient, and as a result, distant tumors regressed.”