Adjuvant adoptive immunotherapy in patients with stage III and resected stage IV melanoma: a pilot study

• Published in: Tumori 2003-07, Vol.89 (4 Suppl), p.298
• Main Authors: Verdecchia, G M, Ridolfi, L, Ridolfi, R, Riccobon, A, Bertagni, A, Vagliasindi, A, Petrini, M, Stefanelli, M, Milandri, C, Amadori, D
• Format: Article
• Language: Italian
• Subjects: Adult; Aged; Cells, Cultured - drug effects; Cells, Cultured - transplantation; Central Nervous System Neoplasms - secondary; Combined Modality Therapy; Disease-Free Survival; Female; Follow-Up Studies; Humans; Immunotherapy, Adoptive; Interleukin-2 - pharmacology; Lung Neoplasms - secondary; Lymphatic Metastasis; Lymphocytes, Tumor-Infiltrating - drug effects; Lymphocytes, Tumor-Infiltrating - transplantation; Male; Melanoma - immunology; Melanoma - secondary; Melanoma - surgery; Melanoma - therapy; Middle Aged; Neoplasm Staging; Pilot Projects; Skin Neoplasms - immunology; Skin Neoplasms - secondary; Skin Neoplasms - surgery; Skin Neoplasms - therapy; Survival Analysis; Treatment Outcome
• ISSN: 0300-8916

Adoptive immunotherapy trials with tumor infiltrating lymphocytes (TIL) and interleukin-2 (IL-2) were carried out in the treatment of advanced melanoma with a 34% of overall responses (OR). However, theoretically it should be of greater benefit as adjuvant therapy, especially in high-risk stages (stage III and resected stage IV). In a pilot study, 22 patients (aged 23-72 years) with stage III-IV melanoma who underwent radical metastasectomy were reinfused with TIL cultivated and expanded in vitro with IL-2 from surgically removed metastases. IL-2 (starting dose 12 x 10(6) IU/m2) was co-administered as a continuous infusion according to West's scheme. A total of 8/22 (36.3%) patients were disease-free (DF) at a median follow-up of 5 years. DF survival (DFS) and overall survival (OS) in the remaining 14 patients were 44% and 37% and 52% and 45% at 2 and 3 years, respectively. The CNS was the only site of disease recurrence in 57% of patients who relapsed. DF patients received a higher median dose of IL-2 than those who progressed (total dose 110 x 10(6) vs 86 x 10(6) IU/m2, respectively). The progressive reduction in IL-2 dosage allowed all patients to complete treatment without permanent grade 4 toxicity. The effects of tumor immunosuppression in lymphocytes inside the tumor (TCR z and e chains, p56lck, FAS and FAS-ligand) confirmed that the potential function of TIL, immunodepressed at the time of metastasectomy, was significantly restored after in vitro, culture with IL-2. Adjuvant adoptive immunotherapy with TIL and IL-2 seems to improve DFS and OS, in comparison with literature data. Further studies are required to determine its role in the adjuvant treatment of patients with high-risk melanoma.