Melanoma and Immunotherapy

By Tyler Kang, MD;                                                     

Summer is a time when the warm weather and long days invite sun worshipers to don their swim gear and head out to the beaches, pools, and other local swimming holes to enjoy the cool waters and soak up some rays. Unfortunately, because of our increasing love of the outdoors and perfectly tanned complexions, our sun exposure and risk of development of skin cancer has increased as well.

Melanoma, the most fatal form of skin cancer, has been steadily increasing in incidence. It has increased by about 3% from 1990s to the 2000s, but in older individuals, the incidence has doubled for men in their 60s from 1983-2007 and quadrupled for men in their 70s. Melanoma is the 5th most common form of cancer in men and 7th in women, and claims about 10,000 lives in the United States each year. In its earliest stages, surgical removal of melanomas can be curative. However, metastatic melanoma can be difficult to treat and often requires systemic therapy in order to control its progression.

Treatment for melanoma, as with most other cancers, has traditionally involved use of chemotherapies. But it is regarded as a universally chemo-resistant disease, with responses only seen in a small number of patients and even those are generally short-lived. Early on in the history melanoma therapy, immunotherapy has been thought of as a potential avenue to treat metastatic melanomas. IL-2 and interferon are immune-modulating agents that, when combined with chemotherapy, led to improved responses and some long-term remissions. However, these therapies were not necessarily easy to tolerate and in fact, were accompanied by severe and sometimes fatal immune mediated reactions.

In the course of the last 5 years, however, several new immunotherapeutic agents have been developed that have improved response rates and survival in this group of patients. Ipilimumab, a first-in-class anti-CTLA4 antibody, demonstrated in a large randomized clinical trial that overall survival was prolonged with therapy and that about 20-30% of patients had long-term remission. Inhibitors of the PD-1 protein, which is an immunosuppressing mechanism present on tumor cells, also showed significant responses in multiple clinical studies. They have demonstrated shrinkage of tumors in up to 40% of patients and have doubled median survivals. These next generation immune therapies are also much better tolerated. Although immune reactions still can take place, patients generally have side effects that are much easier to manage.

Melanomas are aggressive skin cancers that can metastasize and present in advanced stages that are difficult to treat. While new therapies have now improved the prognosis for patients with this disease, the best treatment is often prevention. Appropriate use of sun-screens, protective clothing and hats, especially for those who are more prone to sun’s damaging effects, will go far toward reducing this deadly illness. We can have fun in the sun and take care of our health at the same time.

Dr. Kang is a board certified Medical Oncologist and Hematologist with Epic Care, a group of experts in the diagnosis and comprehensive treatment of cancer and blood disorders.