Fighting Melanoma with Immunotherapy
For this week’s post in our series on melanoma melanoma, Real World Health Care interviewed Kelly M. McMasters, MD, PhD. Dr. McMasters serves as the director of the Multidisciplinary Melanoma Clinic at the University of Louisville’s James Graham Brown Cancer Center. Here, he works with colleagues to identify the most effective combination of therapeutic modalities including surgery, immunotherapies, and targeted therapies for stage I-IV melanoma patients.
Dr. McMasters also directs a basic and translational science laboratory studying adenovirus-mediated cancer gene therapy and melanoma biomarkers, which has been funded by the National Institutes of Health, the American Cancer Society, the Melanoma Research Foundation and other agencies.
Sunbelt Melanoma Trial
Real World Health Care: You are the author and principal investigator of the Sunbelt Melanoma Trial. Can you briefly summarize the focus of this trial and its results?
Kelly McMasters: This was a multi-institutional study involving 3,500 patients from 79 institutions across North America. We studied whether interferon should be used for patients with minimal spread of melanoma to their lymph nodes. We found that this toxic, expensive treatment — which is like having the flu, but worse, for a whole year — was not necessary and did not result in survival benefits. This is important because many patients have been spared unnecessary treatment.
While interferon is still approved for adjuvant therapy for high-risk melanoma, other options now in the pipeline, and further research into the molecular basis of melanoma metastasis and immune system evasion will result in improvements in adjuvant therapy for patients at high risk of recurrence.
We also evaluated molecular tests to find patients at high risk of recurrence, but these tests turned out to not be clinically useful.
RWHC: Are you currently working on any new studies or trials relating to melanoma?
KM: We currently are conducting and participating in several studies of immunotherapy for melanoma. Immunotherapy has revolutionized the treatment of melanoma in the past few years. Five years ago, there were essentially no treatments that were effective for patients with advanced melanoma. Now, we frequently can use immunotherapy that results in durable, complete remissions and even cure in such patients.
Former President Jimmy Carter is an example. He had metastatic melanoma in his brain and elsewhere, with a life expectancy of a few months. He got an immune checkpoint inhibitor and his cancer went away.
Immunotherapy Combinations and Resistance
RWHC: What are some of the biggest challenges facing researchers studying melanoma?
KM: Right now, the challenge is to figure out the best combination of immune therapies to get the greatest benefit for patients with the least side effects. We need to better understand the immune system and how it fights cancer.
Newer studies of melanoma adjuvant therapy using immune checkpoint agents, such as PD-1 inhibitors, show much promise. More work needs to be performed to understand the significance of molecular detection of melanoma cells in the lymph nodes and in the circulating bloodstream. We now suspect that melanoma, like other cancers, routinely sheds cancer cells into the lymphatic system and bloodstream. A small minority of these cells that have the ability to evade the immune system, attach, invade, develop their own blood supply and grow, becoming metastatic tumors.
RWHC: What are some of the biggest challenges facing clinicians studying melanoma?
KM: We need to find out why some patients have miraculous responses to immunotherapy and why some are resistant. Finding out how these mechanisms of resistance work will help us design treatments that are more effective for most people.
Clinicians also need to pay attention to side effects, which are variable, from very mild or virtually none, to potentially life-threatening. Early recognition and treatment — often immediately with corticosteroids — can be lifesaving, especially for autoimmune colitis, which can lead to bowel perforation and serious infection.
RWHC: What interests you in studying melanoma, and treating patients with the disease?
KM: After so many years in which surgery was about the only truly effective treatment for melanoma, it is encouraging to see the development of other effective therapies. I find it gratifying when I now refer patients with advanced melanoma to my medical oncology colleagues for immunotherapy with realistic hope of remission or even cure, rather than engage in desperate attempts to surgically resect all of the cancer. Surgery still has a very important role, but we now have a lot of other possibilities.