Combination of Pembrolizumab with Electrochemotherapy in Cutaneous Metastases from Melanoma: A Comparative Retrospective Study from the InspECT and Slovenian Cancer Registry

Abstract

Electrochemotherapy (ECT) is an effective locoregional therapy for cutaneous melanoma metastases and has been safely combined with immune checkpoint inhibitors in preliminary experiences. Since ECT is known to induce immunogenic cell death, its combination with immune checkpoint inhibitors might be beneficial. In this study, we aimed to investigate the effectiveness of ECT on cutaneous melanoma metastases in combination with pembrolizumab. We undertook a retrospective matched cohort analysis of stage IIIC–IV melanoma patients, included in the International Network for sharing practices of ECT (InspECT) and the Slovenian Cancer Registry. We compared the outcome of patients who received the following treatments: (a) pembrolizumab alone, (b) pembrolizumab plus ECT, and (c) ECT. The groups were matched for age, sex, performance status, and size of skin metastases. The local objective response rate (ORR) was higher in the pembrolizumab-ECT group than in the pembrolizumab group (78% and 39%, p < 0.001). The 1 year local progression-free survival (LPFS) rates were 86% and 51% (p < 0.001), and the 1 year systemic PFS rates were 64% and 39%, respectively (p = 0.034). The 1 year overall survival (OS) rates were 88% and 64%, respectively (p = 0.006). Our results suggest that skin-directed therapy with ECT improves superficial tumor control in melanoma patients treated with pembrolizumab. Interestingly, we observed longer PFS and OS in the pembrolizumab-ECT group than in the pembrolizumab group. These findings warrant prospective confirmation.

Electroporation and Immunotherapy—Unleashing the Abscopal Effect

“…A retrospective study by Heppt et al [ 125 ] of 33 patients with metastatic melanoma showed 15 months median OS among the five patients that received ECT + anti-PD-1, while the median OS in the ECT + ipilimumab group was not reached. The local and systemic objective response rates were comparable to those in the study by Campana et al [ 124 ].…”

“…It found significantly increased OS among the patients that received both local therapy (ECT, radiotherapy, or stereotactic radiation) + ipilimumab (anti-CTLA-4) compared to ipilimumab alone (median OS of 93 weeks vs. 42 weeks), though it should be noted that only 4 in 45 patients received ECT treatment. Recently, the largest retrospective study to date included 130 patients with metastatic melanoma [ 124 ]. Data from the European InspECT group was combined with Slovenian registry data.…”

Treatment of skin tumors with intratumoral interleukin 12 gene electrotransfer in the head and neck region: a first-in-human clinical trial protocol

“…The patients treated with pembrolizumab and ECT experienced lower disease progression rates and longer survival than those who received pembrolizumab alone. 32 Similar approach could be by immunostimulation using phIL12 intratumoral GET. Further, different studies combining tumor irradiation and immune checkpoint inhibitors demonstrated the same.…”

Electrochemotherapy of skin metastases from malignant melanoma: a PRISMA-compliant systematic review

“…However, only four out of 45 enrolled patients were treated with ECT. Finally, Campana et al, in their recent retrospective analysis, showed how Pembrolizumab combined to ECT in melanoma patients (stage IIIC-IV) improves 1-year PFS and OS (p = 0.034 and p = 0.006, respectively) [ 37 ].…”