Immune checkpoint blockade with concurrent electrochemotherapy in advanced melanoma: a retrospective multicenter analysis

Abstract

Growing evidence suggests that concurrent loco-regional and systemic treatment modalities may lead to synergistic anti-tumor effects in advanced melanoma. In this retrospective multicenter study, we evaluate the use of electrochemotherapy (ECT) combined with ipilimumab or PD-1 inhibition. We investigated patients with unresectable or metastatic melanoma who received the combination of ECT and immune checkpoint blockade for distant or cutaneous metastases within 4 weeks. Clinical and laboratory data were collected and analyzed with respect to safety and efficacy. A total of 33 patients from 13 centers were identified with a median follow-up time of 9 months. Twenty-eight patients received ipilimumab, while five patients were treated with a PD-1 inhibitor (pembrolizumab n = 3, nivolumab n = 2). The local overall response rate (ORR) was 66.7 %. The systemic ORR was 19.2 and 40.0 % in the ipilimumab and PD-1 cohort, respectively. The median duration of response was not reached in either group. The median time to disease progression was 2.5 months for the entire population with 2 months for ipilimumab and 5 months for PD-1 blockade. The median overall survival was not reached in patients with ipilimumab and 15 months in the PD-1 group. Severe systemic adverse events were detected in 25.0 % in the ipilimumab group. No treatment-related deaths were observed. This is the first reported evaluation of ECT and simultaneous PD-1 inhibition and the largest published dataset on ECT with concurrent ipilimumab. The local response was lower than reported for ECT only. Ipilimumab combined with ECT was feasible, tolerable and showed a high systemic response rate.

The use of electrochemotherapy in combination with immunotherapy in the treatment of metastatic melanoma: a focused review

“…Another retrospective study by Heppt et al . evaluated the use of ECT with a CTLA‐4 inhibitor (ipilimumab) versus ECT with PD‐1 inhibitors (pembrolizumab or nivolumab) in the treatment of unresectable or metastatic melanoma . A total of 28 patients received ECT with ipilimumab, while a total of five patients received ECT with PD‐1 inhibitors (pembrolizumab n = 3, nivolumab n = 2) .…”

“…However, this immune response does not appear to be robust enough to cause regression of untreated distant tumor nodules . This has led to studies investigating the use of ECT in combination with immunostimulating agents, first in animal models and more recently in humans, to determine if this therapeutic combination could augment the ECT‐induced immunological response and lead to a systemic antitumor response …”

Immune Checkpoint in Glioblastoma: Promising and Challenging

“…Ding et al reported that combined treatment of anti-PD-1 mAb and low-dose chemotherapeutic drugs (cisplatin or paclitaxel) increased anti-cancer efficacy achieved a long-term curative effect (Ding et al, 2014). Additional studies have suggested that immune checkpoint inhibitors, combined with electrochemotherapy, enhanced antitumor benefit in advanced melanoma (Heppt et al, 2016; Hutchinson, 2016). After investigating the impact of radiotherapy (RT), chemotherapy (CT), and RCT on PD-L1 surface expression on different tumor cells, and treating with cells with different chemoradiation therapies, Derer et al found increased PD-L1 expression in certain Melanoma and glioblastoma cells (Derer et al, 2016).…”

Will melanoma be curable? Perspectives in melanoma therapy

“…Az ECT ipilimumabbal tör-ténő kombinációját multicentrikus retrospektív vizsgálatban elemezték. 28 beteg ipilimumab kezelést, 5 beteg PD1-gát-ló kezelést (nivolumab: 3 beteg, pembrolizumab: 2 beteg) kapott az ECT mellett (32). Az utánkövetési idő median érté-ke 9 hónap volt.…”