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High level of soluble programmed cell death ligand 1 in blood impacts overall survival in aggressive diffuse large B-Cell lymphoma: results from a French multicenter clinical trial

Leukemia volume 28, pages 2367–2375 (2014)Cite this article

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Abstract

The dosage of soluble programmed cell death ligand 1 (sPD-L1) protein in the blood of adults with cancer has never been performed in a prospective patient cohort. We evaluated the clinical impact of sPD-L1 level measured at the time of diagnosis for newly diagnosed diffuse large B-cell lymphoma (DLBCL). Soluble PD-L1 was measured in the plasma of 288 patients enrolled in a multicenter, randomized phase III trial that compared R-high-dose chemotherapy with R-CHOP. The median follow-up was 41.4 months. A cutoff of 1.52 ng/ml of PD-L1 level was determined and related to overall survival (OS). Patients with elevated sPD-L1 experienced a poorer prognosis with a 3-year OS of 76% versus 89% (P<0.001). Considering clinical characteristics, the multivariate analysis retained this biomarker besides bone marrow involvement and abnormal lymphocyte–monocyte score as independently related to poor outcome. sPD-L1 was detectable in the plasma and not in the serum, found elevated in patients at diagnosis compared with healthy subjects and its level dropped back to normal value after CR. The intention-to-treat analysis showed that elevated sPD-L1 was associated with a poorer prognosis for patients randomized within the R-CHOP arm (P<0.001). Plasma PD-L1 protein is a potent predicting biomarker in DLBCL and may indicate usefulness of alternative therapeutic strategies using PD-1 axis inhibitors.

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Acknowledgements

This study is supported by the French Health Minister (PHRC2007), the National Institute of Cancer (INCa Translational 2010), GOELAMS, a grant from Roche SAS, France and The European Regional Development Fund (ERDF) 2007–2013. We are indebted to Jean-Jacques Sotto, MD for his support to this project; Imane Azzaoui, Pauline Migaud and Emilie Gougeon for the technical assistance; Roselyne Delepine and Marie-Christine Béné for their efforts in gathering the clinical data; Stéphane Natur for setting the cohorts, the research assistants of the GOELAMS for reviewing the source data; Sami Boussetta for the statistical analysis of the independent cohort; the LYSA pathology platform (Hopital Henri Mondor, Créteil) for immunohistochemical and FISH experiments on paraffin embedded tissue block; the Centre de Ressources Biologiques (CRB)—Santé of the Rennes hospital for providing high quality samples. This work was partly supported by a French National Cancer Institute post-doctoral fellowship (grant number PDOC-RC-GO/07-003] to the first author. In 2012, The Groupe Ouest-Est des Leucémies et des Autres Maladies du Sang (GOELAMS) and The Groupe d’Etude des Lymphomes de l’Adulte (GELA) merged to form the Lymphoma Study Association (LYSA).

Author information

Author notes

  1. G Damaj, A Clavert, A Al Jijakli, A Banos, J-L Dutel, E Deconinck, P Rodon, K Bouabdallah, P Soubeyran, B Choufi, A Maakaroun, O Tournilhac, J Fleury, R Gressin, H Maisonneuve, K Laribi, P Solal-Celigny, P Moreau, J-F Rossi, G Cartron, N Morineau, J L Harousseau, E Jourdan, M Alexis, F Dreyfus, V Delwail, J Cornillon, R Garidi, E Gyan, P Colombat and P Godemer: Members of the Groupe Ouest-Est des Leucémies et des Autres Maladies du Sang (GOELAMS) are listed in the Appendix.

Authors and Affiliations

  1. INSERM U917, Université de Rennes 1, Hôpital Universitaire de Rennes, Rennes, France

    D Rossille, M Gressier, C Pangault, K Tarte, T Lamy & T Fest

  2. Centre de Recherche des Cordeliers, INSERM U872, Université Pierre et Marie Curie and Université Paris-Descartes, Paris, France

    D Damotte

  3. Hospices Civils de Lyon, Service de Biostatistiques, Lyon, France

    D Maucort-Boulch

  4. CNRS UMR 5558, Equipe Biostatistique Santé, Pierre-Bénite, France

    D Maucort-Boulch

  5. Université Lyon I, Villeurbanne, France

    D Maucort-Boulch

  6. INSERM U917, EFS de Bretagne, Rennes, France

    G Semana & K Tarte

  7. Hôpital Universitaire de Nantes, Nantes, France

    S Le Gouill

  8. Service d'hématologie, Hôpital Henri Mondor, Créteil, Paris, France,

    C Haioun

  9. Université de Bordeaux 2, Hôpital Universitaire de Bordeaux-Pessac, Bordeaux, France

    N Milpied

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  1. D Rossille
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Consortia

for the Groupe Ouest-Est des Leucémies et Autres Maladies du Sang

  • G Damaj
  • , A Clavert
  • , A Al Jijakli
  • , A Banos
  • , J-L Dutel
  • , E Deconinck
  • , P Rodon
  • , K Bouabdallah
  • , P Soubeyran
  • , B Choufi
  • , A Maakaroun
  • , O Tournilhac
  • , J Fleury
  • , R Gressin
  • , H Maisonneuve
  • , K Laribi
  • , P Solal-Celigny
  • , P Moreau
  • , J-F Rossi
  • , G Cartron
  • , N Morineau
  • , J L Harousseau
  • , E Jourdan
  • , M Alexis
  • , F Dreyfus
  • , V Delwail
  • , J Cornillon
  • , R Garidi
  • , E Gyan
  • , P Colombat
  •  & P Godemer

Corresponding author

Correspondence to T Fest.

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Competing interests

The authors declare no conflict of interest.

Additional information

The Groupe Ouest-Est des Leucémies et des Autres Maladies du Sang included the following centers and principal investigators in France: G. Damaj, Centre Hospital-Universitaire, Amiens; A. Clavert, Centre Hospital-Universitaire, Angers; A. Al Jijakli, Centre Hospitalier Départemental, Argenteuil; A. Banos, Centre Hospitalier Départemental, Bayonne; J-L. Dutel, Centre Hospitalier Départemental, Beauvais; E. Deconinck, Centre Hospital-Universitaire, Besançon; P. Rodon, Centre Hospitalier Départemental, Blois; K. Bouabdallah, Centre Hospitalo-Universitaire, Bordeaux-Pessac; P. Soubeyran, CRLCC Bergonié, Bordeaux; B. Choufi, Centre Hospitalier Départemental, Boulogne s/mer; A. Maakaroun, Centre Hospitalier Départemental, Bourges; O. Tournilhac, Centre Hospital-Universitaire, Clermont-Ferrand; J Fleury, Pôle Santé République, Clermont-Ferrand; R. Gressin, Centre Hospital-Universitaire, Grenoble; H. Maisonneuve, Centre Hospitalier Départemental, La Roche Sur Yon; K. Laribi, Centre Hospitalier Departemental, Le Mans; P. Solal-Celigny, Clinique Victor Hugo, Le Mans; P. Moreau, Centre Hospitalier Départemental, Lorient; J.-F. Rossi & G. Cartron, Centre Hospital-Universitaire, Montpellier; N. Morineau, Centre Catherine de Sienne, Nantes; J.L. Harousseau, CRLCC Gauducheau, Nantes; E. Jourdan, Centre Hospitalo-Universitaire, Nimes; M. Alexis, Centre Hospitalier Départemental, Orléans; F. Dreyfus, Hôpital Cochin, Paris; V. Delwail, Centre Hospital-Universitaire, Poitiers; J. Cornillon, Institut de Cancérologie de la Loire, St Priest en Jarez; R. Garidi, Centre Hospitalier Départemental, St Quentin en Yvelines; E. Gyan & P. Colombat, Centre Hospital-Universitaire, Tours; and P. Godemer, Centre Hospitalier Départemental, Vannes.

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Rossille, D., Gressier, M., Damotte, D. et al. High level of soluble programmed cell death ligand 1 in blood impacts overall survival in aggressive diffuse large B-Cell lymphoma: results from a French multicenter clinical trial. Leukemia 28, 2367–2375 (2014). https://doi.org/10.1038/leu.2014.137

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