Update: Immunotherapeutic options in advanced melanoma

Dermatologists and dermato-oncologists are playing an increasingly important role not only in diagnosis of melanocytic lesions, but also in the surgical, adjuvant and stage IV treatment of melanoma patients, says Simone Ribero, M.D., Ph.D., of the University of Turin, Italy.

Speaking in a melanoma session at the 26th European Academy of Dermatology and Venereology (EADV) Congress in Geneva, Dr. Ribero said the last seven years of research have changed the history of metastatic melanoma, and the role of dermatology in managing this condition.

“According to their different expertise, many dermatologists are now in the first line facing the metastatic setting of melanoma,” Dr. Ribero said.  

Dr. Ribero

While medical oncology clearly plays a key role in the care of patients with stage IV melanoma, Dr. Ribero emphasized that management by a dedicated dermatologist is appropriate.

“Many dermato-oncologists are directly involved in stage IV (melanoma), making decisions on the particular drug to suggest and enrollment in clinical trials,” he said. “Moreover, the dermatologist is the right specialist to able to recognize and treat skin adverse events, which are very frequent in immunotherapy and targeted therapy.”

Latest research

Dr. Ribero highlighted the latest data on some new drugs that are expanding the range of immunotherapeutic treatment options for advanced melanoma. These include talimogene laherparepvec (T-VEC), the first oncolytic immunotherapy, which is indicated for injection directly into unresectable lesions in patients who have recurrent melanoma after an initial surgery.

Another approach under investigation is inhibition of lymphocyte-activation gene 3 (LAG-3), an immune checkpoint receptor protein found on the cell surface of certain T cells. Investigators recently reported “encouraging initial efficacy” in an early clinical study of the anti-LAG-3 monoclonal antibody BMS-986016, given in combination with nivolumab in patients with melanoma previously treated with immune checkpoint inhibitor therapy.

In addition, the combination or sequencing of established targeted and immune therapies in melanoma is providing additional data of interest. Just three days before EADV, investigators reported in the New England Journal of Medicine, the first analysis of three-year survival data from the CheckMate 067 trial. The results showed that, in patients with advanced melanoma, the combination of nivolumab and ipilumumab resulted in significantly longer overall survival compared with either agent alone.

“New evidence is appearing on this topic almost daily, with survival rates that only a few years ago were totally unbelievable,” Dr. Ribero said.\

Melanoma and nevus count

While Dr. Ribero’s discussion at EADV focused mainly on metastatic disease, some of his best known research is in melanoma genetics and the role of nevus count. In particular, Dr. Ribero and colleagues analyzed a large cohort of melanoma subjects (N = 2,184) and found that high nevus count was associated with better survival, suggesting a unique biological makeup of melanoma tumors in patients with an excess of nevi.

In a separate publication, Dr. Ribero and co-investigators assessed the predictive value of nevus counts in a large cohort of healthy Caucasian female subjects (N = 3,694 female twins); they found that total body nevus count could be estimated quickly by counting nevi on one arm, bolstering previous associations observed in smaller cohorts.