The changes that immunotherapy has brought to the treatment of melanoma
over the last 20 years have been remarkable. What has been the biggest impact
on treatment advances since Interleukin-2 was established for treatment?
The introduction of anti-CTLA-4 had a small impact on patient response, but the single most effective agent for melanoma treatment is anti-PD-1 (nivolumab or pembrolizumab). Using either anti-PD-1 alone or in combination with antiCTLA-4, we can expect 5-year survival for patients with advanced disease to be approximately 50%. Before these agents were available, the 5-year survival rate for our patients was 5-10%. Even more encouraging, many of the patients alive at five years will not relapse and are probably cured of their disease.
You are currently President of the Society for Immunotherapy of Cancer. What are some of the biggest challenges facing the research field as immunotherapy treatments and our knowledge evolves?
The single biggest challenge is to define the mechanisms of resistance, and to be able to identify which of the many possible mechanisms of resistance are responsible for lack of treatment benefit in an individual patient. Without a biomarker to identify why treatment did not work in an individual, it is very difficult to select among the many different potential second line treatments for a patient, and to conduct clinical trials to approve new agents.
What are the research priorities for you and your team for our patients with melanoma?
We are, of course, trying to identify and test new agents, which will benefit the group of patients who don’t receive long-lasting benefit from antiPD-1 and/or anti-CTLA-4 therapies. Part of this effort is to collect tumor samples before and after treatment to understand why treatment is not working. We believe that modifying the function of certain other types of immune cells within the tumor can help a subset of these patients and we are also trying to study various types of cell therapies.
Within our team, Dr. Harriet Kluger is investigating the reasons why melanoma will often form metastases in the brain and is developing new approaches for treating those resistant brain metastases. And of course, not all patients will respond to immune therapies, so our colleagues, including Dr. Ruth Halaban, are focused on new targets based on defining abnormal molecular pathways that drive melanoma cells. Dr. Marcus Bosenberg and Dr. Harriet Kluger lead our NCI SPORE in Skin Cancer grant to translate laboratory findings from their labs and other labs into our clinics.