title: Assessing a novel immuno-oncology-based combination therapy: Ipilimumab plus electrochemotherapy.
abstract: Melanoma is responsible for most skin cancer-related deaths and is one of the most common cancers diagnosed in young adults. In melanoma, tumors can become established by activation of the negative regulator of cytotoxic T lymphocytes (CTLs), CTL antigen-4 (CTLA-4). Ipilimumab blocks the interaction of CTLA-4 with CD80/CD86 and augments T-cell activation and proliferation. In electrochemotherapy (ECT), local application of short high-voltage pulses renders cell membranes transiently permeable to chemotherapeutic drugs. The combination of ipilimumab and ECT may be beneficial for the treatment of metastatic melanoma; however, no prospective data are available to date. Here, we report the retrospective analysis of patients treated with ipilimumab in an expanded access program (EAP) who also received ECT. Fifteen patients with previously treated metastatic melanoma who received ipilimumab 3 mg/kg every three weeks for four cycles and underwent ECT for local disease control and/or palliation of cutaneous lesions with bleomycin 15 mg/m2after the first ipilimumab infusion were included in the analysis. Over the study period, a local objective response was observed in 67% of patients (27% complete response [CR] and 40% partial response [PR]). According to immune-related response criteria, a systemic response was observed in nine patients (five PR and four stable disease [SD]), resulting in a disease control rate of 60%. Evaluation of circulating T-regulatory (T-reg) cells demonstrated significant differences between responders and non-responders. Overall, treatment was well-tolerated and without notable toxicity. In conclusion, the combination of ipilimumab and ECT appears to be beneficial to patients with advanced melanoma, warranting further investigation in prospective trials.
authors.affiliation: Melanoma and Sarcoma Surgery Unit; Istituto Nazionale Tumori Fondazione "G. Pascale" ; Naples, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Mozzillo
authors.affiliation: Melanoma, Cancer Immunotherapy, and Innovative Therapy Unit; Istituto Nazionale Tumori Fondazione "G. Pascale" ; Naples, Italy.
authors.forename: Ester
authors.initials: E
authors.lastname: Simeone
authors.affiliation: Melanoma and Sarcoma Surgery Unit; Istituto Nazionale Tumori Fondazione "G. Pascale" ; Naples, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Benedetto
authors.affiliation: Melanoma, Cancer Immunotherapy, and Innovative Therapy Unit; Istituto Nazionale Tumori Fondazione "G. Pascale" ; Naples, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Curvietto
authors.affiliation: Statistical Unit; Regina Elena National Cancer Institute ; Rome, Italy.
authors.forename: Diana
authors.initials: D
authors.lastname: Giannarelli
authors.affiliation: Melanoma, Cancer Immunotherapy, and Innovative Therapy Unit; Istituto Nazionale Tumori Fondazione "G. Pascale" ; Naples, Italy.
authors.forename: Giusy
authors.initials: G
authors.lastname: Gentilcore
authors.affiliation: Melanoma, Cancer Immunotherapy, and Innovative Therapy Unit; Istituto Nazionale Tumori Fondazione "G. Pascale" ; Naples, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Camerlingo
authors.affiliation: Melanoma, Cancer Immunotherapy, and Innovative Therapy Unit; Istituto Nazionale Tumori Fondazione "G. Pascale" ; Naples, Italy.
authors.forename: Mariaelena
authors.initials: M
authors.lastname: Capone
authors.affiliation: Melanoma, Cancer Immunotherapy, and Innovative Therapy Unit; Istituto Nazionale Tumori Fondazione "G. Pascale" ; Naples, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Madonna
authors.affiliation: Melanoma, Cancer Immunotherapy, and Innovative Therapy Unit; Istituto Nazionale Tumori Fondazione "G. Pascale" ; Naples, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Festino
authors.affiliation: Melanoma and Sarcoma Surgery Unit; Istituto Nazionale Tumori Fondazione "G. Pascale" ; Naples, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Caracò
authors.affiliation: Melanoma and Sarcoma Surgery Unit; Istituto Nazionale Tumori Fondazione "G. Pascale" ; Naples, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Di Monta
authors.affiliation: Melanoma and Sarcoma Surgery Unit; Istituto Nazionale Tumori Fondazione "G. Pascale" ; Naples, Italy.
authors.forename: Ugo
authors.initials: U
authors.lastname: Marone
authors.affiliation: Melanoma and Sarcoma Surgery Unit; Istituto Nazionale Tumori Fondazione "G. Pascale" ; Naples, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Di Marzo
authors.affiliation: Melanoma, Cancer Immunotherapy, and Innovative Therapy Unit; Istituto Nazionale Tumori Fondazione "G. Pascale" ; Naples, Italy.
authors.forename: Antonio M
authors.initials: AM
authors.lastname: Grimaldi
authors.affiliation: Melanoma and Sarcoma Surgery Unit; Istituto Nazionale Tumori Fondazione "G. Pascale" ; Naples, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Mori
authors.affiliation: Scientific Direction; Istituto Nazionale Tumori Fondazione "G. Pascale" ; Naples, Italy.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Ciliberto
authors.affiliation: Melanoma, Cancer Immunotherapy, and Innovative Therapy Unit; Istituto Nazionale Tumori Fondazione "G. Pascale" ; Naples, Italy.
authors.forename: Paolo A
authors.initials: PA
authors.lastname: Ascierto
keywords: Electrochemotherapy; biomarker; immuno-oncology; ipilimumab; melanoma