Recombinant human granulocyte macrophage-colony stimulating factor (rhGM-CSF) and autologous melanoma vaccine mediate tumor regression in patients with metastatic melanoma

In mice, significant immunoprotection was achieved using B16 melanoma cells transfected with granulocyte-macrophage colony-stimulating factor (CM-CSF) as vaccines (Dranoff G, Jaffee E, Lazenby A, et al. Vaccination with irrad iated tumor cells engineered to secrete murine granulocyte-macrophage colon y-stimulating factor stimulates potent, specific, and long-lasting anti-tum or immunity. Proc Natl Acad Sci USA 1993;90:3539-43). The aim of this study is to test the hypothesis that recombinant human GM-CSF (rhGM-CSF) injecte d with autologous melanoma vaccine may result in tumor rejection in melanom a patients, Twenty stage TV melanoma patients were treated as outpatients w ith multiple cycles of autologous melanoma vaccine and bucillus Calmette-Gu erin (BCG) plus rhGM-CSF injection in the vaccine sites. Two patients (10%) showed a complete response, with one patient showing resolution of subcuta neous, hepatic, and splenic metastases. In the second patient, buccal, subc utaneous, pulmonary, paraaortic, hepatic, splenic, and retroperitoneal meta stases regressed completely. Two patients (10%) showed partial response, wi th regression of a paraaortic metastasis in one patient. In the second pati ent, there was shrinkage (>75%) of a large hepatic lesion. One patient has been rendered free of disease after resection of a single pulmonary metasta tic nodule. Three patients (15%) had stable disease during treatment but su bsequently developed progression of disease. In 12 patients (60%), the dise ase progressed. Side effects were minimal. In a separate pilot study, 15 st age IV melanoma patients were also treated with autologous melanoma vaccine with BCG but not with rhGM-CSF; none responded. The Fact that four patient s showed objective responses to active specific immunotherapy with rhGM-CSF demonstrates that melanoma patients bearing a significant tumor burden may respond specifically to their autologous melanoma.