Cancer Immunology, Immunotherapy

, Volume 56, Issue 11, pp 1853–1860

Long-term follow-up of patients treated by adoptive transfer of melanoma tumor-infiltrating lymphocytes as adjuvant therapy for stage III melanoma

  • Amir Khammari
  • Jean-Michel Nguyen
  • Marie Christine Pandolfino
  • Gaëlle Quereux
  • Anabelle Brocard
  • Sylvain Bercegeay
  • Alain Cassidanius
  • Philippe Lemarre
  • Christelle Volteau
  • Nathalie Labarrière
  • Francine Jotereau
  • Brigitte Dréno
Short Communication

DOI: 10.1007/s00262-007-0340-1

Cite this article as:
Khammari, A., Nguyen, JM., Pandolfino, M.C. et al. Cancer Immunol Immunother (2007) 56: 1853. doi:10.1007/s00262-007-0340-1

Abstract

The first analysis of our clinical trial on interest of using tumor-infiltrating lymphocytes (TIL) as adjuvant therapy for stage III (regional lymph nodes) melanoma was published in 2002 [5]. The aim of this paper is to update clinical results of 7 years of follow-up after the last treated patient. In the trial conducted between December 1993 and January 1999, patients without any detectable metastases after lymph node excision were randomly assigned to receive either TIL plus interleukin-2 (IL-2) for 2 months, or IL-2 only. The duration of the relapse-free interval was the primary objective. Eighty-eight patients were enrolled in the study. Currently, the last analysis performed in June 2006, after a median follow-up of 114.8 months, did not show change of non-significant extension of the relapse-free interval or overall survival. However, this second analysis strengthens our first hypothesis about the relationship between number of invaded lymph nodes and TIL treatment effectiveness. In the group with only one invaded lymph node, the estimated relapse rate was significantly lower (Padjusted = 0.0219) and the overall survival was increased (Padjusted = 0.0125) in the TIL+IL-2 arm compared with the IL-2 only arm. No differences between the two arms, either with regard to the duration of disease-free survival (Padjusted = 0.38) or overall survival (Padjusted = 0.43), 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, with a very long follow up (median of almost 10 years), postulates for the first time relationship between TIL efficiency in stage III melanoma (AJCC) and number of invaded lymph nodes, indicating that tumor burden might be a crucial factor in the production of an effective 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.

Keywords

Adjuvant therapy Immunotherapy Tumor-infiltrating lymphocytes Melanoma 

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Amir Khammari
    • 1
  • Jean-Michel Nguyen
    • 2
  • Marie Christine Pandolfino
    • 3
  • Gaëlle Quereux
    • 1
  • Anabelle Brocard
    • 1
  • Sylvain Bercegeay
    • 3
  • Alain Cassidanius
    • 3
  • Philippe Lemarre
    • 3
  • Christelle Volteau
    • 2
  • Nathalie Labarrière
    • 4
  • Francine Jotereau
    • 4
  • Brigitte Dréno
    • 1
    • 3
  1. 1.Skin Cancer UnitCHU Hôtel DieuNantes Cedex 01France
  2. 2.PIMESP, CHU NantesHôpital St. JacquesNantesFrance
  3. 3.Cellular and Genetic Therapy UnitCHU NantesNantesFrance
  4. 4.INSERM U601 NantesNantesFrance