Importance of the timing of combined electrochemotherapy and immunotherapy in the treatment of advanced melanoma.

Published data on the combination of immunotherapy and electrochemotherapy (ECT) consistently indicate a benefit in tumor response, but an important question, the optimal timing for combination, remains unclear. We investigated the impact of the timing of the ECT/immunotherapy combination. A cohort of 170 stage IIIC–IV melanoma patients from the Insp-ECT registry were evaluated for toxicity and local, systemic and long-term responses after combined ECT/immunotherapy treatment. Three groups were compared: patients who received immunotherapy before, during and after ECT. Combined treatment with ECT did not increase the toxicity profile of ECT. The best response was achieved with concomitant treatment with ECT. After 2 months, the local response was 61% CR and 20% PR, the systemic response was 27% CR and 17% PR, and the RFS was 87% after 12 months and 66% after 24 months. All groups had poorer results if compared with concomitant combined treatment, and when immunotherapy was given before ECT, a significantly worse response was detected. This study shows that the best time for ECT is during immunotherapy with immune checkpoint inhibitors. Our study indicates that ECT could be associated with increased benefits of immunotherapies, potentially influencing the response rate of melanoma patients to immunotherapy.