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. Immunotherapy treats the whole body by attempting to activate a person’s immune system so that it will destroy any melanoma cells within the body.
Immunotherapy is prescribed and administered by a medical oncologist in a variety of ways, most commonly by using biologic agents that stimulate the immune system. Other mechanisms are currently under investigation in clinical trials and include vaccine therapy, intra-lesional therapy, stem cell manipulation and others.
Immune Stimulants, FDA approved
Commonly prescribed immune stimulants include biologic agents such as antibodies, interferons and interleukins, which are administered in much higher doses than are usually present in the body.
- Pembrolizumab (Keytruda) received accelerated approval in 2014 for demonstrating durable responses in patients whose disease has progressed following ipilimumab and, if BRAF V600 mutation positive, also a BRAF inhibitor. Randomized trials are in progress to assess the ability of pembrolizumab to improve time to progression and overall survival.
- Ipilimumab (Yervoy), which stimulates T cells, was approved by the FDA in 2011. It was the first drug in 13 years to be approved for the treatment of metastatic melanoma. Randomized trials have shown an improvement in overall survival in patients with either previously treated or untreated advanced melanoma. Patients and physicians should be aware that immune-mediated toxicities may be severe so good communication with your physician will allow early identification and successful treatment. Common side effects include: tiredness, diarrhea, itching and rash.
- Interferon alpha 2-b is the FDA-approved standard treatment for patients with metastatic melanoma that has been surgically resected and that are at high risk for recurrence (i.e., for adjuvant therapy). Analyses of randomized trials of interferon used in an adjuvant setting show that it can lengthen the time of melanoma recurrence, but it does not appear to prolong survival.
- Interleukin-2 (IL-2) was the first immunotherapy to be approved for metastatic melanoma (1998) and was approved on the basis of long-lasting complete response. Randomized trials of IL-2 have not been conducted, so precise information on long-term overall survival is not available.
Immune Stimulants, currently in Clinical Trials
- Ipilimumab (Yervoy) is now in clinical trials being tested as adjuvant therapy for patients whose melanoma has been completely resected.
- Many trials are testing combinations of immune stimulants, including ipilimumab, interferon, IL-2 and others to see if the single agent responses, when used together, can increase.
Many other biologic agents are currently under development as single agents and in combination. Anti-PD-1 and anti-PD-L1 antibodies, which activate T cells and are in the category of checkpoint inhibitors, such as ipilimumab, have promising early data and one has been this year.
Other Immune Stimulants
Other immune stimulating agents that have been used in the treatment of melanoma include Bacillus Calmette-Guerin (BCG), Corynebacterium parvum and the immunomodulator levamisole.