Immunotherapy 'Plus': Adding Radiation and Chemo to Immune Therapies

Robert H. Carlson, MBA

Disclosures

June 27, 2016

In This Article

The Promise of the Abscopal Effect

There are established reasons to try. One is the "abscopal effect" (ab meaning "away from," and scopus meaning "target"), a synergy between radiation and immunotherapy in which local radiotherapy is associated with regression of metastatic cancer in sites that were not irradiated. The thinking is that radiation primes the immune system to recognize tumor-specific targets as cells are dying, which is then translated into a systemic effect.

Researchers at Memorial Sloan Kettering Cancer Center in 2012 reported a surprising systemic response after local radiotherapy in combination with the checkpoint inhibitor ipilimumab in a patient with metastatic melanoma.[1]

The patient experienced tumor shrinkage, changes in peripheral blood immune cells, and antibody responses, effects the investigators speculated may be mediated by activation of the immune system via the abscopal effect.

Senior author Jedd Wolchok, MD, PhD, chief of melanoma and the immunotherapeutics service at Memorial Sloan Kettering Cancer Center, said in an interview that clinical trials are now underway exploring the abscopal effect prospectively.

"This is a very important area of focus," he said. "Even though radiation therapy may only treat a few tumors at a time, this could serve as a vaccination effect and change the tumor microenvironment. Then the addition of checkpoint blocking therapies might lead to a more robust antitumor effect."

A similar effect may be achieved by combining stereotactic body radiation therapy (SBRT) with immune checkpoint inhibitors.

Eric Bernicker, MD, clinical service chief of hematology/oncology and director of medical thoracic oncology at Houston Methodist Cancer Center, said that only 20%-25% of patients with lung cancer respond robustly to immune checkpoint inhibitors as monotherapy.

SBRT may change the microenvironment and open up more antigens, priming T cells for a more robust response when immunotherapy is started, Dr Bernicker said.

"There is preclinical data on SBRT with ipilimumab and some case reports showing that response," he said. "Over the next year we'll start getting data from trials that are now open on whether there is truly a synergistic result."

"Obviously if that starts looking very promising, it could be that indiscriminate cytotoxics are going to be used less and less—and no one would be sad if we have to use less chemotherapy."

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