A phase I trial of repeated tumour-infiltrating lymphocyte (TIL) infusion in metastatic melanoma.
The aim of the protocol was to evaluate the side-effects induced by repeated 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 patients) and weekly (4 patients). All patients were evaluated and received a total of 34 TIL infusions. The total number of TILs administered varied from 0.65 to 2.34 x 10(11) cells. TIL phenotypes were predominantly CD8+ (two patients), CD4+ (4 patients), CD4+ then CD8+ (two patients) or CD56+ (two patient). Autocytotoxicity was only observed 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 patients). Hypotension was constantly seen in patients who were given TILs every 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 partial response on a tumour site for 1-4 months. Three patients presented signs of inflammation or softening at one tumour site. Plasma tumour 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 when TIL infusions were performed weekly. An increase in circulating TNF-alpha was noted after TIL infusion.
Ravaud
A
A
Department of Medical Oncology, Fondation Bergonié, Comprehensive Cancer Centre, Bordeaux, France.
Legrand
E
E
Delaunay
M M
MM
Bussières
E
E
Coulon
V
V
Cany
L
L
Huet
S
S
Verdier
D
D
Kind
M
M
Chomy
F
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007022:Hypotension / Q000209:etiology; D016219:Immunotherapy, Adoptive / Q000009:adverse effects; D016246:Lymphocytes, Tumor-Infiltrating; D008297:Male; D008545:Melanoma / Q000097:blood / Q000276:immunology / Q000556:secondary* / Q000628:therapy; D008875:Middle Aged; D010166:Palliative Care; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D014409:Tumor Necrosis Factor-alpha