Potential dual synergy between electrochemotherapy and sequence of immunotherapies in metastatic melanoma: A case report.

Immune checkpoint inhibitors have changed the natural history of advanced melanoma. Despite this, a notable proportion of patients immediately relapse or develop resistance during immunotherapy, especially with the appearance of superficial metastases and consequently with a dramatic impact on clinical outcomes. Local treatment by electrochemotherapy (ECT), parallel to regional control with palliative aim, seems to release neoantigens potentially determining a significant systemic anticancer immune reactivation. The present study reported a case of a patient with metastatic melanoma receiving Pembrolizumab, electrochemotherapy and then Ipilimumab for in-transit and finally locoregional lymph nodes and distant bone metastases with experience of clinic-radiological remission. Specifically, the present patient progressed during adjuvant treatment with in-transit metastases on the scalp; he underwent two cycle of ECT obtaining partial and then unexpected and very fast nearly complete response with the Ipilimumab treatment. Concomitantly, he developed grade 4 endocrine adverse events (hypophysitis and diabetes mellitus type I) as immune-related toxicities. At 12 months from ECT the patient is in ECOG Performance Status 0 and he has resumed a regular social life. In our experience, ECT in two administrations increased and accelerated the response of Ipilimumab. The present confirmed its promising contribution in inducing a powerful immune response in order to overcome primary or acquired resistance to immune checkpoint inhibitors such as anti-programmed death antigen-1 drugs.