Benefit of adjuvant interferon alfa-2b (IFN-α) therapy in melanoma patients with high serum MMP-8 levels

• Published in: Cancer Immunology, Immunotherapy Vol. 64; no. 2; pp. 173 - 180
• Main Authors: Vihinen, Pia, Tervahartiala, Taina, Sorsa, Timo, Hansson, Johan, Bastholt, Lars, Aamdal, Steinar, Stierner, Ulrika, Pyrhönen, Seppo, Syrjänen, Kari, Lundin, Johan, Hernberg, Micaela
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.02.2015; Springer Nature B.V
• Subjects: Adolescent; Adult; Aged; Antineoplastic Agents - therapeutic use; Cancer; Cancer Research; Chemotherapy, Adjuvant; Cytokines; Female; Hospitals; Humans; Immunology; Interferon; Interferon alpha-2; Interferon-alpha - therapeutic use; Male; Matrix Metalloproteinase 8 - blood; Medical prognosis; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Melanoma; Melanoma - blood; Melanoma - drug therapy; Melanoma - mortality; Melanoma - pathology; Middle Aged; Neoplasm Staging; Neuroblastoma; Oncology; Original; Original Article; Prognosis; Radiation therapy; Recombinant Proteins - therapeutic use; Sarcoma; Treatment Outcome; Young Adult; Sweden; Finland; MMP; Serum; Prognosis; Survival; Melanoma; Adjuvant interferon
• ISSN: 0340-7004; 1432-0851; 1432-0851
• DOI: 10.1007/s00262-014-1620-1

Matrix metalloproteinases (MMPs) are important enzymes in tissue turnover and various inflammatory processes. In this study, it was evaluated whether serum MMP-8 can predict the response to adjuvant interferon alfa-2b (IFN-α) therapy in patients with operated high-risk cutaneous melanoma. Pre-treatment sera from 460 patients with stage IIB–IIIC melanoma were analyzed for MMP-8. The patients were randomized after surgery to adjuvant IFN-α for 12 or 24 months ( n  = 313) or observation only ( n  = 147). The median serum MMP-8 level was used to classify the patients into a low MMP-8 ( n  = 232) and a high MMP-8 ( n  = 228) group. In the high MMP-8 subgroup, IFN-α therapy significantly improved relapse-free survival (RFS). RFS was 36.8 months in patients with high MMP-8 levels receiving IFN-α therapy, whereas RFS for those with high MMP-8 levels with observation only was 10.6 months ( P  = 0.027). Median overall survival for patients with high MMP-8 and observation only was 36.7 versus 71.7 months in those receiving IFN-α ( P  = 0.13). In a multivariate model, IFN-α therapy was a significant predictor of favorable RFS (HR 0.74; 95 % CI 0.55–0.99; P  = 0.048), after adjustment for pre-treatment MMP-8 (HR 1.17; 95 % CI 0.88–1.55; P  = 0.28), gender (HR 1.16; 95 % CI 0.86–1.56; P  = 0.32), age (HR 1.00; 95 % CI 1.00–1.02; P  = 0.12), ulceration (HR 1.09; 95 % CI 0.81–1.46; P  = 0.58), and the presence of node metastases (HR 1.36; 95 % CI 1.17–1.58; P  < 0.0001). In conclusion, patients with high serum MMP-8 levels may benefit from adjuvant IFN-α therapy, but this observation should be further investigated.