Melanoma Treatment - Immunotherapy

Immunotherapy is a type of systemic therapy useful in the treatment of melanoma at high risk for recurrence and for metastatic melanoma. The goal of immunotherapy is to treat the whole body. Immunotherapy is given in an attempt to activate a person’s own immune system so that it will destroy any melanoma cells within the body.

Immunotherapy Medical Oncology Team

Immunotherapy is prescribed and administered by a medical oncologist.

Immunotherapy can be given in a variety of ways. The most well known way in melanoma is by using biologic agents that stimulate the immune system. Other mechanisms of stimulating the immune system are currently under investigation through clinical trials and include vaccine therapy, stem cell manipulation, among others.

Immune Stimulants

Commonly prescribed immune stimulants include the biologic agents, the interferons and interleukins. These agents are administered in much higher doses than are usually present in the body. Common side effects include flu-like symptoms.

• Yervoy ("ipilimumab" or "ipi") was approved on March 25, 2011 and was the first drug in 13 years to be approved for the treatment of melanoma. Yervoy is a monoclonal antibody that binds to CTLA-4, an inhibitory molecule on T lymphocytes. T lymphocytes are blood cells that may be highly effective in inhibiting cancer growth. When CTLA-4 on T lymphocytes binds to CD80 on tumor antigen-presenting cells (APC), activation of the T cells by tumor antigen, and thus the capacity of the T cells to destroy tumor cells expressing the antigen, is inhibited (see figure). When Yervoy binds to CTLA-4 on T cells, the brake is released and T cells can become activated and destroy tumor cells. 
• Interferon alpha 2-b is the FDA-approved standard treatment for patients with metastatic melanoma. As this treatment induces significant adverse reactions in most patients, an abbreviated treatment regimen of 12 weeks was evaluated for clinical efficacy.  Its approved dosing schedule is one month of high dose intravenous therapy followed by 11 months of sub-cutaneous injections. There are many side effects associated with Interferon therapy. On-going clinical trials are investigating its use in earlier stage melanoma as well as alternate dosing schedules.
• Interleukin-2 (IL-2) has been used for the treatment of melanoma with modest success for several decades. In recent trials, IL-2 has been combined with other cytokines, such as GM-CSF (granulocyte, macrophage, colony stimulating factor). However, clinical response rates were not increased by adding GM-CSF to IL-2.      Its approved dosing schedule is 2 cycles of high dose intravenous therapy, requiring hospitalization, administered in specialized medical centers. There are many acute toxicities associated with Interleukin therapy and extremely close monitoring is essential for safe administration.

Other immune stimulating agents that have been used in the treatment of melanoma include Bacillus Calmette-Guerin (BCG), Corynebacterium parvum, and the immunomodulator levamisole.