Immunotherapy
For Melanoma

Immunotherapy for Melanoma: Transforming Patient Outcomes

Reviewed by:

Jedd D. Wolchok, MD, PhD
Weill Cornell Medicine

Immunotherapy has dramatically shifted the treatment landscape for melanoma, significantly enhancing survival rates and offering new hope to those battling this formidable form of skin cancer. Although melanoma represents a relatively small percentage of all skin cancer diagnoses, it’s the leading cause of skin cancer deaths, largely because of its propensity to spread beyond the skin to other organs. 

The advent of checkpoint inhibitors has been a game-changer, particularly for those facing metastatic melanoma, marking a pivotal shift towards more optimistic outcomes for patients. It’s anticipated that there will be over 100,000 new cases of melanoma in the United States in 2024, with an estimated 8,200 expected to die because of melanoma. Men are at a higher risk of diagnosis than women. 

Remarkably, the death rates from melanoma have been on a significant decline between 2013 and 2017, a testament to the progress in treatment methodologies. This positive trajectory highlights the impact of early detection and the introduction of innovative therapies like immunotherapy, contributing to a more hopeful future for individuals diagnosed with melanoma.

Understanding Melanoma and Its Risk Factors

Melanoma arises in the pigment-producing cells of the skin, known as melanocytes, but can also form in the eye—a condition known as uveal melanoma. The primary risk factor for developing melanoma is exposure to ultraviolet (UV) light from the sun or artificial sources, such as tanning beds. Early detection is pivotal for improving survival rates, as melanoma tends to metastasize more rapidly than other types of skin cancer.

The Role of Immunotherapy in Melanoma Treatment

Immunotherapy leverages the body’s immune system to identify and attack cancer cells, marking a significant shift from traditional treatments like surgery and chemotherapy. The FDA has approved several immunotherapy treatments for melanoma, targeting various aspects of the immune response:

Targeted Antibodies

• Tebentafusp-tebn (Kimmtrak®): a bispecific antibody that targets the gp100 protein on tumor cells and CD3 on T cells; approved for subsets of patients with melanoma.

Immunomodulators

• 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, as part of a tumor agnostic approval, for subsets of patients with advanced melanoma that has DNA mismatch repair deficiency (dMMR).
• 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.
• 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 (post-surgical) setting.
• Relatlimab: a checkpoint inhibitor that targets the LAG-3 pathway; approved in combination with nivolumab (together known as Opdualag™) for subsets of patients with melanoma.

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.

Advancements and Awareness

With melanoma’s profound impact on lives worldwide, Melanoma Awareness Month begins on May 1st. This observance is dedicated to amplifying awareness, offering unwavering support to those affected, and underscoring the necessity for ongoing research and clinical trials. It’s a time to unite in our efforts to combat melanoma, encouraging early detection, prevention, and the development of more effective treatments.

Research into immunotherapy for melanoma continues to evolve, with CRI playing a crucial role in funding innovative studies. The organization has supported the development of breakthrough treatments through clinical trials, enhancing our understanding of melanoma and how best to fight it.

FAQs: Immunotherapy for Melanoma

How effective is immunotherapy for melanoma?

A recent study published by the National Institutes of Health (NIH) shows that immunotherapy improves survival rates for many melanoma patients. Specifically, treatments like PD-1 inhibitors have increased the 5-year survival rate for advanced melanoma patients to approximately 50%. The effectiveness of immunotherapy can vary, influenced by factors such as the tumor’s characteristics and the patient’s immune response.

How long does immunotherapy for melanoma last?

The duration of immunotherapy for melanoma depends on the patient’s response to treatment and the specific drugs used. Some patients may receive immunotherapy for two years, while others might continue as long as they are benefiting from the treatment without severe side effects.

How often is treatment administered?

The frequency of immunotherapy administration can vary widely depending on the specific regimen. Common schedules include every two, three, or four weeks. The exact schedule is determined by the type of immunotherapy used, the patient’s health status, and how well the cancer responds to treatment.

What are the best immunotherapy treatments for melanoma?

The “best” immunotherapy for melanoma depends on various factors, including the stage of cancer and the patient’s overall health. Commonly used and effective treatments include checkpoint inhibitors like pembrolizumab (Keytruda), nivolumab (Opdivo), and ipilimumab (Yervoy), sometimes used in combination for enhanced effectiveness.

What are the side effects of immunotherapy for melanoma?

While often less severe than chemotherapy, side effects can range from mild to severe and may include fatigue, skin rash, itchiness, flu-like symptoms, and more serious conditions like organ inflammation. The severity of side effects varies from patient to patient, and close monitoring by healthcare providers is essential to manage them effectively.

CRI’s Impact in Melanoma

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 support innovative research in melanoma immunotherapy—from lab to clinic to cures.

• Padmanee Sharma, MD, PhD, and colleagues discovered a cellular pathway called ICOS. The sustained activation of this pathway on T cells in response to ipilimumab treatment 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 tested 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, MD, PhD. The trial results showed that the experimental antibody TRX-518 was  safe and well tolerated by patients, paving the way for further multidose studies to determine the efficacy of the vaccine against cancer. 
• CRI investigator Timothy N.J. Bullock, PhD, 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, MD, 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, PhD, 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.

Join the Fight Against Melanoma

As we continue to make strides in immunotherapy research, the support of our community remains invaluable. With each donation, we edge closer to turning the tide against melanoma, moving towards a future where this cancer can be effectively managed or even cured.

Explore more about melanoma-specific research funded by CRI and how you can contribute to this cause. Together, we can make a difference in the lives of those affected by melanoma.