Perilesional Injection of r-GM-CSF in Patients with Cutaneous Melanoma Metastases

Abstract

Based on evidence that granulocyte-macrophage colony stimulating factor (GM-CSF) induces a potent systemic antitumor immunity, we tested recombinant GM-CSF in advanced melanoma. Seven patients with histologically confirmed cutaneous melanoma metastases were treated with perilesional intracutaneous injections of recombinant GM-CSF and observed for a follow-up time of 5 y. All but two patients had a decrease in the total number of metastases. At the end of the 5 y follow-up three of the seven patients are still alive with only one patient receiving other than surgical therapy, and one patient died tumor free at the age of 93. The remaining three patients died from progressive melanoma. Perilesional intradermal GM-CSF therapy resulted in a mean survival time of 33 mo. The treatment was well tolerated and no side-effects other than local erythema at the injection sites and mild drowsiness were seen. Immunohistochemical analysis with staining for CD14 and GM-CSF receptor demonstrated an increased infiltration of monocytes into both injected and noninjected cutaneous melanoma metastases compared with lesions excised prior to the initiation of therapy. The same was true for CD4- and CD8-positive lymphocytes. This phenomenon, together with GM-CSF-induced leukocyte counts of more than 20,000 during therapy, support the possible impact of a systemic over a locally induced reaction by GM-CSF. To our knowledge this is the first report that intracutaneously injected GM-CSF results in long-lasting reduction of melanoma metastases.

Isolated Limb Perfusion for Malignant Melanoma: Systematic Review on Effectiveness and Safety

“…Regarding palliative radiotherapy, despite the lack of studies on the benefit of radiotherapy in locally advanced melanoma, hypofractionated regimens obtain CR rates of up to 59% in stage I-III patients, including cases of in-transit metastases [41,42]. Other locoregional therapeutic options tested in locally advanced melanoma patients (intralesional interleukin-2, perilesional GM-CSF, electrochemotherapy) need to be investigated in larger comparative series before discussing their role in the management of this clinical entity [43][44][45][46][47]. As for survival, the multivariate analysis completed in several studies also rendered interesting results.…”

Current status of granulocyte–macrophage colony-stimulating factor in the immunotherapy of melanoma

“…Clinical responses in two of these studies were modest, with only one partial response (PR) and no complete response (CR) reported [44,45]. In contrast, a study using perilesional injection of GM-CSF (400 μg/d over 5 days) to treat metastatic melanoma described reduced lesion size in 6/7 patients and a reduction in cutaneous metastases in 5/7 patients [46]. Three patients were still alive at 5-years follow-up; a fourth died tumor-free at age 93.…”

Melanoma, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology

“…[98][99][100][101] These studies and others led to the development of T-VEC, an agent that uses a modified herpes simplex virus to induce tumor cell lysis and to deliver localized expression of GM-CSF to injected lesions. 102 A recent phase 3 trial in select patients with unresectable stage IIIB-IV melanoma randomized subjects to intralesional injection of T-VEC versus subcutaneous injection of GM-CSF.…”