Immunotherapy of melanoma: present options and future promises

The authors reviewed current and future immunotherapies for the treatment of melanoma. 

In the advanced stages of melanoma (stage III/IV), cancer spreads rapidly from the skin to other parts of the body. This is known as metastasis. Conventional cancer treatments such as radiotherapy (directs a beam of radiation at the tumor site to kill cancer cells) and chemotherapy are not effective in the advanced stages of this disease. Immunotherapy is an alternative treatment option. Recently, it has shown significant treatment benefits in advanced melanoma. Immunotherapy uses the body’s own immune system to fight cancer. There are two approved immunotherapies for advanced melanoma. These are Ipilimumab (Yervoy) and high dose of interleukin-2 (Proleukin). Treatment with these drugs has shown long-term survival benefits in advanced melanoma that cannot be surgically removed.

A more comprehensive review on immunotherapies is required to decide the appropriate treatment options for melanoma patients.

The authors aimed to review current and future immunotherapies for the treatment of advanced melanoma.

Currently approved immunotherapies:

p-IFN α-2b (Sylatron) has been approved for the treatment of advanced melanoma. It is mainly recommended as an additional treatment in advanced melanoma that can still be surgically treated.

Ipilimumab is recommended as the primary treatment for inoperable stage IV melanoma in patients with poor general well being. Additionally, patients should not have mutations (permanent change) in the BRAF genes. BRAF genes are important proteins used in cellular signaling. Ipilimumab is recommended as a secondary treatment for patients who have good general well being, regardless of the BRAF mutation status. The limitation of ipilimumab is the poor response rate in patients (how fast the tumors are decreasing in size). In a study, only 2-4% of patients had a partial response (some tumor shrinkage) or complete response (tumor completely disappeared) and 50-60% did not show any response to ipilimumab treatment. Several clinical trials on ipilimumab in combination with other therapies (such as radiation) are currently on going.

Future treatment options:

Sargramostim (Leukine) is another immunotherapy. It consists of immune cells that are important in cell signaling. Treatment of melanoma with sargramostim alone or with chemotherapy has been met with some success. A phase III clinical trial of sargramostim alone or with other drugs has recently been completed.

Immunotherapy with dendritic cells may be a promising treatment for advanced melanoma. Dendritic cells are important components in the immune system. There are currently 13 phase I/II on-going clinical trials involving dendritic cells.

Challenges of immunotherapies:

The response rate to immunotherapy is low. This is mainly due to the compromised immune systems of patients. The presence of other disease conditions, old age and the cost of immunotherapy may also influence treatment response. 60% of patients treated with immunotherapy experience side-effects. These include nausea, diarrhea, inflammation of the colon, fatigue and liver problems, among others.

The authors concluded that immunotherapy has the potential to increase long-term survival in melanoma patients. However, certain factors need to be considered when deciding on this therapy. These include the patient’s immune system, psychological stress and financial status, among others.