Melanoma, immunotherapy and survival: the ‘revolution’ of the trio of drugs

L’immunotherapy against melanoma rises to the next level. In fact, to the now consolidated administration of one or two immunotherapy drugs together, which has already changed the history of the disease, is added a brand new combination – a ‘super immunotherapy’ – which involves the use of all three drugs simultaneously. The trio of molecules nivolumab, relatlimab and ipilimumab, all immune checkpoint inhibitors, capable of removing the ‘brakes’ from the immune system against melanoma, brings the survival rate of patients with advanced melanoma, followed for more than 4 years, to 72%. More than 20% of what drugs administered alone or in pairs would do.

Opening up to this new frontier of immunotherapy is Lo study ‘Relativity-048’, led by Paolo Ascierto, president of the Melanoma Foundation and director of the Melanoma Oncology Unit, Oncological Immunotherapy and Innovative Therapies of the Pascale Institute, conducted in collaboration with the universities of Zurich, Aix-Marseille, Lausanne, Oxford and The Sidney Kimmel Comprehensive Cancer Center of Johns Hopkins Medicine. The preliminary results have just been presented at the annual meeting of ASCO, the American Society of Clinical Oncology, underway in Chicago.

“These are preliminary data – Ascierto immediately points out – but very encouraging which concern patients with forms of advanced inoperable melanoma, with the presence of liver and brain metastases, therefore with a rather unfavorable prognosis. In our study the immunotherapeutic triplet proved promising, achieving approximately 60% responses and certainly deserves to be investigated in larger clinical trials.”

I study

The Relativity-048 study involved 46 patients with advanced melanoma and an average age of 61 years. Patients received the triple combination of nivolumab, relatlimab and ipilimumab for an average duration of 5 months and were then followed for an average of 49.4 months. “We recorded a disease survival rate of 72% at 4 years, higher than that observed with other therapeutic regimens that involve the administration of two immunotherapeutics – underlines Ascierto – In 20% of patients we recorded a complete remission”.

The data on the safety of the treatment are also very encouraging. “Surprisingly, the toxicity is almost comparable to that of treatment in combination with two immunotherapeutics, ipilimumab-nivolimab, and no further adverse events emerged,” specifies Ascierto, who nevertheless urges caution.

“Ours is a preliminary study that involved a limited number of patients – he concludes -. For this reason, the results should be interpreted with caution and should be confirmed in larger studies, which could also allow us greater precision in the selection of patients who would benefit the most from this triple combination.”