Immunotherapy for melanoma has changed the way this cancer is treated. In particular, checkpoint inhibitors are responsible for the increasing survival rate for patients with metastatic melanoma.
Although melanoma comprises less than five percent of all skin cancers, it accounts for the vast majority of deaths caused by skin cancer. Melanoma is a cancer that most often arises in the pigment-producing melanocytes found in the skin, but there is also a form called uveal melanoma which can develop in the eye.
As with all skin cancers, the main risk factor for melanoma is exposure to UV light—both natural and artificial sunlight. According to the American Academy of Dermatology, more people develop skin cancer from tanning than develop lung cancer from smoking.
While melanoma is typically easier to detect in earlier stages than in many other types of cancer, it is also much more likely to metastasize, or spread to other organ systems of the body. For this reason, survival rates for localized (stage 1 and 2) melanoma and metastasized melanoma vary greatly.
Unfortunately, instances of melanoma skin cancer are on the rise globally. Approximately 290,000 people are diagnosed with the disease each year, in addition to about 61,000 deaths. In the United States alone, there will be an estimated 106,000 new cases in 2021, in addition to roughly 7,000 deaths. The five-year survival rate for localized (stage 1 and 2) melanoma is 98 percent; however, this drops to 23 percent in cases where cancer has metastasized to distant sites or organs. (These numbers are based on historical data collected up to 2011, and may change as immunotherapy is more widely used.)
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Current protocol for melanoma treatment depends on the prognosis at time of disease detection. When caught early, the melanoma tumor may be removed during surgery, but if a biopsy shows that the melanoma has spread to lymph nodes, the treatment strategy may include more intensive surgery, targeted therapy, radiation, immunotherapy, and/or clinical trials.
Immunotherapy is class of treatments that take advantage of a person’s own immune system to help kill cancer cells. There are currently nine FDA-approved immunotherapy options for melanoma.
- Aldesleukin (Proleukin®): a cytokine that targets the IL-2/IL-2R pathway; approved for patients with advanced melanoma
- Atezolizumab (Tecentriq®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved in combination with cobimetinib and vemurafenib for a subset of patients with advanced melanoma
- Dostarlimab (Jemperli): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced melanoma that has DNA mismatch repair deficiency (dMMR)
- Interferon alfa-2b (Intron A®): a cytokine that targets the IFNAR1/2 pathway; approved for subsets of patients with melanoma
- Ipilimumab (Yervoy®): a checkpoint inhibitor that targets the CTLA-4 pathway; approved for subsets of patients with advanced melanoma, including as a first-line therapy and in combination with nivolumab
- Nivolumab (Opdivo®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced melanoma, including in combination with ipilimumab
- Peginterferon alfa-2b (Sylatron®/PEG-Intron®): a cytokine that targets the IFNAR1 pathway; approved for subsets of patients with melanoma
- Pembrolizumab (Keytruda®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced melanoma, including in the adjuvant (pre-surgical) setting
Oncolytic Virus Therapy
- T-VEC (Imlygic®): a modified herpes simplex virus (HSV) that infects tumor cells and promotes their destruction; approved for subsets of patients with advanced melanoma
Despite the recent advancements in FDA-approved melanoma therapies, many advanced metastatic melanoma patients still face a significant mortality risk. The aggressive nature of this disease sustains an urgent need for more successful, effective melanoma immunotherapies.
Find a melanoma clinical trial
For more than three decades, CRI has funded laboratory and clinical research into the development of melanoma immunotherapies—granting nearly $38 million to the fight against this deadly skin cancer. This financial support has effectively funded more than 35 clinical trials enrolling roughly 750 melanoma patients, helping to advance the field of treatment through better insight and understanding of the disease.
Melanoma is a core focus of ongoing immunotherapy research done by CRI scientists. With the help of our donor community, our organization continues to supports innovative research in the field of melanoma immunotherapy—from lab to clinic to cures.
- Padmanee Sharma, M.D., Ph.D., and colleagues discovered a cellular pathway called ICOS whose activation on T cells in response to ipilimumab treatment, and the sustained activation of this pathway, may explain why some patients respond better to therapy than others.
- Through CRI’s venture philanthropy program, a phase 1 trial in melanoma and other cancers is testing the experimental antibody GITR (the first treatment of its kind to be tested in human cancer patients) to enhance the activity of T cells against cancer at Memorial Sloan Kettering Cancer Center under the direction of Jedd D. Wolchok, M.D., Ph.D.
- CRI investigator Timothy N.J. Bullock, Ph.D., at the University of Virginia Health System, showed that a monoclonal antibody designed to activate the CD27 costimulatory molecule, which plays an important role in the activation, survival, and differentiation of T cells, significantly reduced the progression of metastases and primary tumors in a mouse model of melanoma.
- Clinical trials investigator Hassane Zarour, M.D., and colleagues at the University of Pittsburgh Cancer Institute found that cells that express both the TIM-3 and PD-1 molecules constituted a highly dysfunctional subset of tumor-specific killer T cells in patients with advanced melanoma.
- CRI postdoctoral fellow Li Tang, Ph.D., of MIT, developed a novel technique using nanotechnology in melanoma and other cancers to deliver immune-stimulating chemicals called cytokines directly to the site of tumors.
See what melanoma-specific research we’re currently funding. With your help, we can fund more research and revolutionize the way melanoma is treated—saving more lives.
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