Melanoma is a type of skin cancer that’s quite common—and quite treatable. In fact, in most cases, melanoma is caught early enough that we can remove the affected area with surgery; after that, the patient is considered cancer-free. That’s why it’s so important that patients talk to their doctors immediately after noticing a change in an existing mole’s shape, feel, or color. However, sometimes melanoma isn’t found right away and the cancer may invade other areas of the body, like the lymph nodes or blood. In these cases, treatment beyond surgery is required. Today, new treatment options like immunotherapy are giving some of these patients with advanced melanoma long-lasting and effective results. In the past, metastatic melanoma patients would undergo chemotherapy and radiation to fight their cancer, suffering from difficult side effects, often without success. Over the last few decades, we have advanced tremendously in our treatment of melanoma; now, chemo is rarely used and radiation is only used in very specific situations. Instead, we turn to targeted therapies and immunotherapies, which are much easier for patients to tolerate and more effective for many people. Melanoma: A Pioneer for Immunotherapy Immunotherapy uses your own immune system to fight your cancer. Yes, that should be happening automatically, but we’ve discovered that cancer cells hide themselves from immune fighter cells. Cancer cells use molecules called checkpoints to trick the immune cells into thinking they’re friends, not foes. Your immune system might be working very hard, but it just won’t recognize the cancer cells as invaders, and thus won’t send an army to destroy them. However, in recent years, scientists have developed checkpoint inhibitors—a type of immunotherapy that reveals cancer cells to the immune system. And checkpoint inhibitors were first studied in melanoma patients, with positive results. Melanoma was the first cancer treated with immunotherapies for several reasons. For a long time, we didn’t have reliable treatment for advanced melanoma. If melanoma couldn’t be removed surgically, and didn’t respond to chemo or radiation, patients didn’t have many options. Because of this, researchers worked hard to fill the void, and there were many patients interested in participating in clinical trials. First, they tried medications that stimulated the immune system, but those were only effective for about 10% of patients. Then, targeted therapies were introduced; this technique was (and is) successful for some patients, but not all. Today, for applicable patients, the U.S. Food and Drug Administration (FDA) has approved four different targeted therapies to treat melanoma, and we still typically turn to targeted therapies first before immunotherapies. Finally, checkpoint inhibitors came into play in the last few years. Since 2011, three of these drugs have been approved by the FDA—ipilimumab (Yervoy), pembrolizumab (Keytruda), and nivolumab (Opdivo). They stop cancer cells from hiding from the immune system. These new drugs are incredibly effective and patients who respond can live long lives free from melanoma. Right now, only about 30 to 40% of patients respond to checkpoint inhibitor immunotherapies—so it doesn’t yet work for everyone. But when it works, it shows remarkable success, with fairly manageable side effects like fatigue and diarrhea. More than a third of patients treated with these immunotherapies are alive five years after starting treatment—that’s twice the number of patients alive five years after treatment with other methods. And clinical trials happening now are showing that the combination of two different checkpoint inhibitors works in 50% of patients (although side effects are harder to manage). Right now, immunotherapies are so new that we don’t know exactly how long patients will live disease-free. However, some of the earliest treated patients are still cancer free more than 10 years later, so that’s a good sign. Immunotherapies: Still Many Unknowns When it comes to immunotherapies, the first thing we experts in the field think is, “wow, isn’t this wonderful?” However, two immediate questions follow that: “Why don’t more patients respond to immunotherapy?” and “How do we make the effects of immunotherapy last even longer?” Some patients live cancer-free for years, while others do not. There’s a lot more we need to learn. But for the individual patient who benefits from these treatments, it’s incredible.