title: Randomized trial of adoptive transfer of melanoma tumor-infiltrating lymphocytes as adjuvant therapy for stage III melanoma.
abstract: The aim of this study was to demonstrate the interest of using tumor-infiltrating lymphocytes (TIL) as adjuvant therapy for stage III (regional lymph nodes) melanoma. After lymph node excision, patients without any detectable metastases were randomly assigned to receive either TIL plus interleukin-2 (IL-2) for 2 months, or IL-2 only. The primary endpoint was determination of the duration of the relapse-free interval. Eighty-eight patients determined as eligible for treatment were enrolled in the study. After a median follow-up of 46.9 months, for the study population the analysis did not show a significant extension of the relapse-free interval or overall survival. However, a significant interaction ( P<0.001) was found between the treatment and the number of invaded lymph nodes. In the group with only one invaded lymph node, the estimated relapse rate was significantly lower ( P(adjusted)=0.0285) and the overall survival was increased ( P(adjusted)=0.039) in the TIL+IL-2 arm compared with the IL-2 only arm. No differences between the two arms, either as regards the duration of disease-free survival or overall survival, were noted in the group with more than one invaded lymph node whatever the number of invaded lymph nodes. Treatment was compatible with normal daily activity. This study demonstrates for the first time that the efficiency of TIL in stage III melanoma (AJCC) is directly related to the number of invaded lymph nodes, indicating that tumor burden might be a crucial factor in the efficacy and/or in vitro expansion of T cells specific for autologous tumor antigen, a finding which could be of value in future vaccine development for the treatment of melanoma.
authors.affiliation: Skin Cancer Unit, CHR Hôtel Dieu, Nantes, 44093 Nantes, France. bdreno@wanadoo.fr
authors.forename: Brigitte
authors.initials: B
authors.lastname: Dréno
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Nguyen
authors.forename: Amir
authors.initials: A
authors.lastname: Khammari
authors.forename: Marie Christine
authors.initials: MC
authors.lastname: Pandolfino
authors.forename: Marie Hélène
authors.initials: MH
authors.lastname: Tessier
authors.forename: Sylvain
authors.initials: S
authors.lastname: Bercegeay
authors.forename: Alain
authors.initials: A
authors.lastname: Cassidanius
authors.forename: Philippe
authors.initials: P
authors.lastname: Lemarre
authors.forename: Sylviane
authors.initials: S
authors.lastname: Billaudel
authors.forename: Nathalie
authors.initials: N
authors.lastname: Labarrière
authors.forename: Francine
authors.initials: F
authors.lastname: Jotereau
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000627:therapeutic use; D008207:Lymphatic Metastasis; D016246:Lymphocytes, Tumor-Infiltrating / Q000637:transplantation*; D008297:Male; D008545:Melanoma / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D008875:Middle Aged; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D007376:Interleukin-2