Adjuvant immunotherapy with tumor infiltrating lymphocytes and interleukin-2 in patients with resected stage III and IV melanoma.

Abstract

Adoptive immunotherapy with tumor infiltrating lymphocytes (TIL) and interleukin (IL)-2 is reasonably effective in the treatment of patients with advanced melanoma. However, theoretically it should be of greater benefit as adjuvant therapy, especially in high-risk stages (resected stages III and IV). In a preliminary study, 25 patients (aged 23-72 years) with stage III-IV melanoma who underwent resection of metachronous metastases were reinfused with TIL cultivated and expanded in vitro with IL-2 from surgically removed metastases. IL-2 (starting dose 12 x 10 IU/m ) was co-administered as a continuous infusion according to West's scheme. A total of 8/22 (36.3%) evaluable patients were disease-free (DF) at a median follow-up of 5 years. DF survival (DFS) and overall survival (OS) rates were 44% and 37%, respectively, at 2 years, and 52% and 45% at 3 years. 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 versus 86 x 10 IU/m, respectively). The progressive reduction in IL-2 dosage allowed all patients to complete treatment without permanent grade 4 toxicity. Analysis of tumor immunosuppression factors in lymphocytes inside the tumor (TCR zeta and epsilon chains, p56, FAS, and FAS-ligand) confirmed that the immunologic potential of TIL, depressed at the time of metastasectomy, was significantly restored after in vitro culture with IL-2. Adoptive immunotherapy with TIL and IL-2 could improve DFS and OS, although further work is required to determine its role in the treatment of patients with high-risk melanoma.

• Authors: Laura Ridolfi, Ruggero Ridolfi, Angela Riccobon, Franca De Paola, Massimiliano Petrini, Monica Stefanelli, Emanuela Flamini, Alessandra Ravaioli, Giorgio Maria Verdecchia, Giusto Trevisan, Dino Amadori
• Journal: Journal of immunotherapy (Hagerstown, Md. : 1997) (J Immunother) 2003 Mar-Apr Vol. 26 Issue 2 Pg. 156-62 ISSN: 1524-9557 [Print] United States
• PMID: 12616107 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Adjuvants, Immunologic
• Interleukin-2

Topics

• Adjuvants, Immunologic (administration & dosage)
• Adult
• Aged
• Biopsy, Needle
• Combined Modality Therapy
• Dose-Response Relationship, Drug
• Female
• Humans
• Immunotherapy, Adoptive (methods)
• Infusions, Intravenous
• Interleukin-2 (administration & dosage)
• Lymphocytes, Tumor-Infiltrating (transplantation)
• Male
• Melanoma (mortality, pathology, surgery, therapy)
• Middle Aged
• Neoplasm Staging
• Probability
• Prognosis
• Prospective Studies
• Risk Assessment
• Skin Neoplasms (mortality, pathology, surgery, therapy)
• Statistics, Nonparametric
• Survival Analysis
• Treatment Outcome