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Melanoma A Game-Changing Drug in the Fight against Melanoma STORY HIGHLIGHTS Pembrolizumab is the first in a new class of cancer therapies known as programmed cell death inhibitors, which work by releasing the brake to the immune system to attack malignant cells. Pembrolizumab has been shown to benefit patients whose cancer had spread anywhere in the body, and the incidence of side effects was found to be relatively low. In September, the U.S. Food and Drug Administration approved a new drug for treating advanced melanoma. The medication is the first in an exciting new class of cancer therapies known as programmed cell death inhibitors. Antoni Ribas, MD, PhD, a UCLA oncologist, was the principal investigator on the study of pembrolizumab (Keytruda) that led to its approval. Dr. Ribas describes the significance of the new medication. What is pembrolizumab, and how does it work? It’s the first member of a new class of cancer therapeutics that works by releasing a brake to the immune system. The immune system can recognize and attack the cancer, but there’s a leash on it because our evolution has decided that we don’t want the immune system attacking normal organs. The cancer hides behind that mechanism by expressing a protein called PD-L1, which limits an immune response. We disable this brake, and then the immune system can attack the tumor. Antoni Ribas, MD UCLAHEALTH.ORG 1-800-UCLA-888 (1-800-825-2888) Have researchers been working on this idea for a long time? The concept of taking off the brakes to the immune system has been around for about 20 years. It led to the first antibody that was approved for treating melanoma, called ipilimumab, or Yervoy, which was licensed four years ago. That drug provided the proof of concept, but it was not that effective and there were side effects in patients. With pembrolizumab, we get better responses and fewer side effects. So the concept was started with ipilimumab, but now we have a better target. How effective was the drug in your clinical trial? One-third of the patients with metastatic melanoma responded long term to this agent alone. Another third had some tumor shrinkage, but not enough and the disease eventually progressed. Other immunotherapies like interleukin-2 and interferon could lead