title: 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.affiliation: Istituto Oncologico Romagnola, Pierantoni Hospital, Forli, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Ridolfi
authors.forename: Ruggero
authors.initials: R
authors.lastname: Ridolfi
authors.forename: Angela
authors.initials: A
authors.lastname: Riccobon
authors.forename: Franca
authors.initials: F
authors.lastname: De Paola
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Petrini
authors.forename: Monica
authors.initials: M
authors.lastname: Stefanelli
authors.forename: Emanuela
authors.initials: E
authors.lastname: Flamini
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ravaioli
authors.forename: Giorgio Maria
authors.initials: GM
authors.lastname: Verdecchia
authors.forename: Giusto
authors.initials: G
authors.lastname: Trevisan
authors.forename: Dino
authors.initials: D
authors.lastname: Amadori
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D001707:Biopsy, Needle; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage*; D016246:Lymphocytes, Tumor-Infiltrating / Q000637:transplantation*; D008297:Male; D008545:Melanoma / Q000401:mortality / Q000473:pathology* / Q000601:surgery / Q000628:therapy*; D008875:Middle Aged; D009367:Neoplasm Staging; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D012878:Skin Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery / Q000628:therapy*; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D007376:Interleukin-2