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Tumor infiltrating lymphocytes as adjuvant treatment in stage III melanoma patients with only one invaded lymph node after complete resection: results from a multicentre, randomized clinical phase III trial

  • Clinical Trial Report
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Abstract

Background

Adoptive tumor-infiltrating lymphocytes (TIL) therapy and interleukin-2 (IL-2) have been investigated in melanoma.

Aim

To confirm previously observed preventive effects of TIL + IL2 in a subgroup of patients with relapsing metastatic stage III melanoma.

Methodology

Open-label, randomized two-group, multicenter five-year trial in adult stage III melanoma patients with only one invaded lymph node after complete resection. Patients received TIL + IL2 or abstention. TIL + IL2 was administered within 8 weeks after lymph node resection and 4 weeks after. Disease-free survival was assessed every 2 months up to month 18, every 3 months up to month 36 and every 4 months up to 5 years. A once-a-year follow-up was scheduled beyond the five-year follow-up. Safety was assessed throughout the trial.

Results

Overall, 49 patients accounted for the modified intent-to-treat and 47 for the PP. Slightly more male than female patients participated; mean age was 57.7 ± 11.4 years in the TIL + IL2 group and 53.5 ± 13.0 years in the abstention group. After 5 years of follow-up, 11/26 patients in the TIL + IL2 group and 13/23 in the abstention group had relapsed. There was no statistical difference between the groups (HR: 0.63 CI 95% [0.28–1.41], p = 0.258), nine patients in the TIL + IL2 and 11 in the abstention group died with no significant difference between the two groups (HR: 0.65 CI95% [0.27 − 1.59], p = 0.34). Safety was good.

Conclusion

We did not confirm results of a previous trial. However, ulceration of the primary melanoma may be considered predictive of the efficacy of TIL in melanoma in adjuvant setting, in a manner similar to interferon α.

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Acknowledgements

The authors acknowledge the participation of the patients in this clinical trial and the writing and editing support of Karl Patrick Göritz, SMWS—Scientific and Medical Writing Services, France.

Funding

This study was performed within the LabEX IGO program, supported by the National Research Agency via the investment of the future program ANR-11-LABX-0016-01. Chiron France kindly provided interleukin-2.

Author information

Authors and Affiliations

  1. Dermato-cancérology Department, CHU Nantes, CIC 1413, CRCINA, INSERM, University of Nantes, CHU Nantes-Hôtel-Dieu, 1 Place Alexis Ricordeau, 44093, Nantes Cedex 01, France

    Amir Khammari, Gaëlle Quéreux & Brigitte Dréno

  2. SEME, PHU11, Saint-Jacques Hospital, CRCINA, INSERM, University of Nantes, Nantes, France

    Jean-Michel Nguyen

  3. Department of Dermatology, Allergology and Photobiology, CHU A Michallon, Grenoble, France

    Marie-Thérèse Leccia

  4. Département of Dermatology, University of Montpellier, CHU de Montpellier, Montpellier, France

    Bernard Guillot

  5. UTCG, CHU Nantes, Nantes, France

    Soraya Saiagh, Marie-Christine Pandolfino & Brigitte Dréno

  6. CRCINA, INSERM, University of Angers, University of Nantes, Nantes, France

    Anne-Chantal Knol & Nathalie Labarrière

  7. Pharmacovigilance Department, CHU Nantes, Nantes, France

    Anne Chiffolettau

  8. LabEx IGO “Immunotherapy, Graft, Oncology”, Nantes, France

    Nathalie Labarrière

Authors
  1. Amir Khammari
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  2. Jean-Michel Nguyen
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  7. Anne-Chantal Knol
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  10. Nathalie Labarrière
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  11. Brigitte Dréno
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Corresponding author

Correspondence to Brigitte Dréno.

Ethics declarations

The trial complied with all French (AgenceNationale de Sécurité du Médicament et des Produits de Santé, ANSM,” Loi n° 2012–300, 5 Mars2012 relative aux recherchesimpliquant la personnehumaine” and all its amendments) and European requirements for the conduct of clinical trials (EuroepanMedicinec Agency, EMA, CPMP/ICH/377/95, EMEA) and the principles of Good Clinical Practices, the 1964 Declaration of Helsinki, received approval for all study sites from the ethics committee of Nantes, France in December 2003 (CPP Ouest IV Nantes n° 553/2005) and is registered at ClinicalTrials.gov under the Identifier: NCT00200577. All patients provided written informed consent prior to inclusion.

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The authors have no conflict of interest to disclose.

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This paper reports results from an open-label, randomized two-group, multicenter five-year trial in adult stage III melanoma patients with only one invaded lymph node after complete resection.

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Khammari, A., Nguyen, JM., Leccia, MT. et al. Tumor infiltrating lymphocytes as adjuvant treatment in stage III melanoma patients with only one invaded lymph node after complete resection: results from a multicentre, randomized clinical phase III trial. Cancer Immunol Immunother 69, 1663–1672 (2020). https://doi.org/10.1007/s00262-020-02572-1

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