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

J Immunother. Mar-Apr 2003;26(2):156-62. doi: 10.1097/00002371-200303000-00008.

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.

Publication types

  • Comparative Study

MeSH terms

  • 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
  • Melanoma / pathology*
  • Melanoma / surgery
  • Melanoma / therapy*
  • Middle Aged
  • Neoplasm Staging
  • Probability
  • Prognosis
  • Prospective Studies
  • Risk Assessment
  • Skin Neoplasms / mortality
  • Skin Neoplasms / pathology*
  • Skin Neoplasms / surgery
  • Skin Neoplasms / therapy*
  • Statistics, Nonparametric
  • Survival Analysis
  • Treatment Outcome

Substances

  • Adjuvants, Immunologic
  • Interleukin-2