Cancer Immunology, Immunotherapy

, Volume 51, Issue 10, pp 539–546

Randomized trial of adoptive transfer of melanoma tumor-infiltrating lymphocytes as adjuvant therapy for stage III melanoma

  • Brigitte Dréno
  • Jean-Michel Nguyen
  • Amir Khammari
  • Marie Pandolfino
  • Marie Tessier
  • Sylvain Bercegeay
  • Alain Cassidanius
  • Philippe Lemarre
  • Sylviane Billaudel
  • Nathalie Labarrière
  • Francine Jotereau
Original Article

DOI: 10.1007/s00262-002-0315-1

Cite this article as:
Dréno, B., Nguyen, JM., Khammari, A. et al. Cancer Immunol Immunother (2002) 51: 539. doi:10.1007/s00262-002-0315-1

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 (Padjusted=0.0285) and the overall survival was increased (Padjusted=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.

Adjuvant therapy Immunotherapy Melanoma 

Copyright information

© Springer-Verlag 2002

Authors and Affiliations

  • Brigitte Dréno
    • 1
  • Jean-Michel Nguyen
    • 2
  • Amir Khammari
    • 1
  • Marie Pandolfino
    • 3
  • Marie Tessier
    • 1
  • Sylvain Bercegeay
    • 3
  • Alain Cassidanius
    • 3
  • Philippe Lemarre
    • 3
  • Sylviane Billaudel
    • 4
  • Nathalie Labarrière
    • 5
  • Francine Jotereau
    • 5
  1. 1.Skin Cancer Unit, CHR Hôtel Dieu, Nantes, Place Alexis Ricordeau, 44093 Nantes Cedex 01, France
  2. 2.PIMESP, CHR Nantes, Hôpital St. Jacques, 85, rue St. Jacques, 44093 Nantes, France
  3. 3.Cellular and Genetic Therapy Unit, CHR Nantes, 9 Quai Moncousu, 44093 Nantes, France
  4. 4.Department of Virology, CHU Nantes, Place Alexis Ricordeau, 44093 Nantes, France
  5. 5.INSERM U463 Nantes, 9 Quai Moncousu, 44093 Nantes, France