A PHASE-I TRIAL OF REPEATED TUMOR-INFILTRATING LYMPHOCYTE (TIL) INFUSION IN METASTATIC MELANOMA

The aim of the protocol was to evaluate the side-effects induced by re peated tumour-infiltrating lymphocyte (TIL) infusions in patients with metastatic melanoma (MM). Patients were to receive four TIL infusions at given intervals: every 3 weeks (two patients), every 2 weeks (3 pa tients) and weekly (4 patients). All patients were evaluated and recei ved a total of 34 TIL infusions. The total number of TILs administered varied from 0.65 to 2.35 x 10(11) cells. TIL phenotypes were predomin antly CD8(+) (two patients), CD4(+) (4 patients), CD4(+) then CD8(+) ( two patients) or CD56(+) (two patient). Autocytotoxicity was only obse rved for one culture. Six patients presented at least one WHO grade 3 side-effect: hypotension (5 patients), dyspnoea (two patients), fever (one patient), fatigue (one patient), chills (two patients), diarrhoea (one patient), agitation (one patient), locoregional pain (two patien ts). Hypotension was constantly seen in patients who were given TILs e very week. Two cases of minor pericarditis were recorded. No objective response to treatment was observed; 1 stable disease occurred in one patient and progression in eight. However, five patients presented a p artial response on a tumour site for 1-4 months. Three patients presen ted signs of inflammation or softening at one tumour site. Plasma tumo ur necrosis factor alpha (TNF-alpha) levels were increased 1.2- to 22- fold after TIL infusion. TILs could be produced in sufficient quantity to perform this study, so repetitive infusions of TIL became possible on a weekly basis. However, no objective response was observed even w hen TIL infusions were performed weekly. An increase in circulating TN F-alpha was noted after TIL infusion.