Long-term Survivors among Patients with Metastatic Melanoma Treated with Targeted Agents And/or Checkpoint Inhibitors

Background: Long-term survival for patients with metastatic melanoma (MM) was very rare until the advent of targeted and checkpoint inhibitor therapy. Today clinical trial data provide evidence of encouraging 3-year and even 5-year survival rates, while real-world data are lacking. Methods: Patient and disease characteristics were collected among MM patients treated in a reference oncology center since 2012 with targeted and/or checkpoint inhibitor agents. We defined long-term survivors as patients with survival >2years from MM diagnosis; biological material was collected for genomic analyses. Results: From 130 MM patients treated with BRAF/MEK inhibitors and/or anti-CTLA4, anti-PD1 agents in any line, 25 long-term survivors were identified (19,2%), 15 men/ 10 women. Long-term survival was characterized by good prognosis features at initial diagnosis: median PS 0, normal LDH (60%), low disease burden (≤3 metastatic sites, 88%), median Distant Metastasis Free Interval (DMFI) 3 years (range 0-23+ years), 16/25 BRAF mutant MM. All long-term survivors had achieved an objective response (complete/partial) to targeted or immuno- therapy. Objective response was associated with long-term survival regardless of treatment line. Complete responses to targeted or immunotherapy are still ongoing (2 to immunotherapy >3 years, 2 to BRAF/MEKi >5 years). Most patients are alive today (21/25, 84%): 9 patients (36%) survive >5 years from MM diagnosis, with 8 of them (32%) surviving >5 years from new therapy initiation (targeted or immuno). The majority of patients (22/25, 88%) survive >3 years from initial MM diagnosis and 76% survive >3 years from therapy initiation (targeted or immuno-), suggesting that the long-term survival benefit is due to the new therapy. Genomic analysis will complement the clinical characteristics of long-term survival. Conclusions: A significant number of patients with MM treated in a reference center achieved long-term survival with targeted or immuno-therapy. The specific clinical and genomic characteristics of these long-term survivors can improve our understanding of the biological behaviour of the disease but also assist the optimal choice and use of new therapies. Legal entity responsible for the study: Oncology Department, Metropolitan Hospital, Athens. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.