Assessing a novel immuno-oncology-based combination therapy: Ipilimumab plus electrochemotherapy

Nicola Mozzillo, Ester Simeone, Lucia Benedetto, Marcello Curvietto, Diana Giannarelli, Giusy Gentilcore, Rosa Camerlingo, Mariaelena Capone, Gabriele Madonna, Lucia Festino, Corrado Caracò, Gianluca Di Monta, Ugo Marone, Massimiliano Di Marzo, Antonio M. Grimaldi, Stefano Mori, Gennaro Ciliberto, Paolo A. Ascierto

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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/m2 after 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.

Original languageEnglish
JournalOncoImmunology
Volume4
Issue number6
DOIs
Publication statusPublished - 1 Jan 2015
Externally publishedYes

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Keywords

  • Biomarker
  • Electrochemotherapy
  • Immuno-oncology
  • Ipilimumab
  • Melanoma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

Cite this

Mozzillo, N., Simeone, E., Benedetto, L., Curvietto, M., Giannarelli, D., Gentilcore, G., Camerlingo, R., Capone, M., Madonna, G., Festino, L., Caracò, C., Di Monta, G., Marone, U., Di Marzo, M., Grimaldi, A. M., Mori, S., Ciliberto, G., & Ascierto, P. A. (2015). Assessing a novel immuno-oncology-based combination therapy: Ipilimumab plus electrochemotherapy. OncoImmunology, 4(6). https://doi.org/10.1080/2162402X.2015.1008842