Radiation Blast May Turbocharge Bristol-Myers Melanoma Drug

Radiating one tumor can trigger the immune system to wipe out tumors in other parts of the body and may boost the effectiveness of Bristol-Myers Squibb Co. (BMY)’s cancer drug Yervoy, doctors have shown.

Researchers at Memorial Sloan-Kettering Cancer Center are reporting on the case of a 41-year-old woman with advanced melanoma who took Yervoy, a drug that stimulates the immune system to fight cancer cells, in a clinical trial. She didn’t respond to the medicine until she got a radiation treatment to shrink a tumor on her lung that was pressing on a nerve and causing severe back pain.

Soon, all the other tumors in her body started shrinking, according to the results published in the New England Journal of Medicine. The case is the best demonstration to date of a rare phenomenon called the abscopal effect, in which radiation to just one tumor causes other tumors all over the body to regress, said Charles Drake, a medical oncologist at the Johns Hopkins University School of Medicine not involved with the study.

“It is a really amazing finding,” Drake said in a phone interview. “It confirms that this effect can occur.”

The broad tumor shrinkage was associated with changes in the immune system that occurred after the radiation treatment, according to the report.

Harnessing the effect may enable researchers to boost the response rate to Yervoy, said Memorial Sloan-Kettering’s Jedd Wolchok, an oncologist and senior author on the case study. The radiation-linked response may occur because the radiation creates cellular debris that the immune system recognizes as dangerous, he said.

Immune System Brakes

Yervoy for melanoma is the first in a new class of drugs that removes molecular brakes on immune system cells that prevent them from attacking cancer. While it improves survival by four months, the drug causes major tumor shrinkage in 10 to 15 percent of melanoma patients. Doctors are looking for a way to improve on this.

Valerie Esposito, the radiation patient in the study, started getting Yervoy in September 2009 and didn’t clearly benefit at first. “She was definitely getting worse” until she got the radiation in December 2010, said Wolchok.

Yet when doctors performed a scan a few months after the radiation, six tumors in her spleen and two more in her lymph nodes that had not been radiated shrank dramatically, he said.

Surprise Phone Call

Wolchok called Esposito with the news as she was driving home from an appointment at the cancer center last spring.

“He was like, you won’t believe it, but your tumors shrunk drastically,” Esposito said in a phone interview. “It is amazing, it is a wonderful thing.”

Esposito, a government clerical worker and single mother raising three kids on Long Island near New York City, said she hopes her case can provide clues for doctors how to help other melanoma patients.

Wolchok said that a second melanoma patient on Yervoy at Memorial Sloan-Kettering had a similar body-wide response to local radiation treatment just a few weeks ago.

Wolchok, who is also affiliated with the Ludwig Institute for Cancer Research in New York, is working with several major hospitals to start a clinical trial that would combine Yervoy and radiation to see if doctors can duplicate what happened to Esposito on broader numbers of patients, he said. It could begin in six months.

Sarah Koenig, a spokeswoman for Bristol-Myers Squibb Co., based in New York, said in an e-mail that the company is aware of the Sloan-Kettering case report and considers it “an interesting finding.”

Bristol-Myers is studying whether Yervoy’s effects can be enhanced with radiation, she wrote. One example of this is a trial the company is conducting of Yervoy in patients who have received radiation for advanced prostate cancer, she said.

Yervoy generated $360 million for Bristol-Myers in 2011, according to data compiled by Bloomberg.

To contact the reporter on this story: Robert Langreth in New York at +1-212-617-1886 or rlangreth@bloomberg.net

To contact the editor responsible for this story: Reg Gale in New York +1-212-617-2563 or rgale5@bloomberg.net

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