Immunotherapy for melanoma

Melanoma therapy has recently seen significant progress, with several new drugs in phase II/III trials showing promising results. In this review, we discuss the most promising immunotherapies either already established or being developed, concentrating on agents for which there are high-level data to support or refute their role in treating this disease. This topic is timely, given the lengthy list of immune checkpoint inhibitors and vaccine formulations in development for melanoma.

The discovery of immune checkpoint proteins like CTLA-4, PD-1 and CD40 and the development of antibodies and small molecules that either inhibit or promote their activity has lent a huge impetus to the immunotherapy of melanoma. The development of vaccines that include agonists of various immune signaling like the MAGE-3 ASCI has also revived the field of cancer vaccines. Melanoma is the 'poster child' for immunotherapy of cancer, since a recent randomized phase III trial showed a survival benefit for immunotherapy.

The burgeoning field of immunotherapy for melanoma has important implications for clinicians, and for the novel paradigms of treatment and response assessment that immunotherapies will promote. The unique side-effect profile for immune checkpoint inhibitors will be a challenge but new skills for dealing with them in community based practice will be learned. The concept that physicians might see late regression, or progression followed by regression will cause a sea-change in the way patients are treated, since treating beyond progression may be suitable in some cases using immunotherapy.