Lenalidomide maintenance fails to overcome the unfavourable prognosis of low NK‐cell counts in rituximab–chemotherapy responsive elderly DLBCL patients: A LYSA group study

Author:

Beldi‐Ferchiou Asma1ORCID,Jais Jean‐Philippe2,Ghesquieres Hervé3ORCID,Casasnovas Rene Olivier4,Tilly Hervé5,Fruchart Christophe6,Morschhauser Franck7,Haioun Corinne8,Lazarovici Julien9,Perrot Aurore10,Nicolas‐Virelizier Emmanuelle11,Salles Gilles3,Godard Nathalie1,Zamali Imen1,De Colella Jean‐Marc Schiano12,Claudel Alexis1,Corront Bernadette13,Oberic Lucie14ORCID,Briere Josette15,Gaulard Philippe1617,Thieblemont Catherine18,Delfau‐Larue Marie‐Hélène1

Affiliation:

1. Biological Hematology and Immunology department, APHP, INSERM U 955 Hopital Henri Mondor Creteil France

2. Biostatistics Unit, APHP Univ Paris Descartes Paris France

3. Hematology, Centre Hospitalier Lyon Sud PIERRE‐BENITE Lyon France

4. Hematology, CHU Dijon Bourgogne and INSERM U 1231 Dijon France

5. INSERM U918, Centre Henri Becquerel Rouen France

6. Institut d'Hématologie de Basse Normandie, CHU Caen Caen France

7. Clinical Hematology, Univ. Lille, CHU Lille, ULR 7365 ‐ GRITA ‐ Groupe de Recherche sur les formes Injectables et les Technologies Associées Lille France

8. Lymphoid Malignancies Unit, APHP Hopital Henri Mondor Creteil France

9. Clinical Hematology Gustave Roussy Cancer Center Villejuif France

10. Hematology department, CHU Brabois Vandoeuvre les Nancy France

11. Onco Hematology, Centre Leon Berard Lyon France

12. Onco Hematology, Institut Paoli Calmettes Marseille France

13. Hematology, CH Annecy Genevois Epagny Metz‐Tessy France

14. Hematology, IUC ‐ Oncopole CHU Toulouse Toulouse France

15. Pathology, APHP, Hopital Saint‐Louis Paris France

16. AP‐HP, Henri Mondor Hospital, Pathology Department Créteil France

17. Univ Paris Est Créteil, INSERM, IMRB Créteil France

18. Assistante publique – Hôpitaux de Paris, Hôpital Saint‐Louis, Hemato‐oncologie, DMU DHI Université de Paris Paris France

Abstract

SummaryLow baseline NK‐cell counts (NKCCs) in patients with diffuse large B‐cell lymphoma (DLBCL) are associated with a poor prognosis. The REMARC phase III trial (NCT01122472) showed that lenalidomide maintenance prolonged PFS in rituximab–chemotherapy responders. We conducted a REMARC ancillary study analysing the impact of lenalidomide maintenance on the prognostic value of low NKCCs. Blood samples from 335 elderly French patients enrolled in the REMARC trial were analysed by flow cytometry to obtain NKCCs at diagnosis (n = 220), at randomization (n = 186) and/or six months after randomization (n = 184). Baseline NKCCs < 100 cells/μl were associated with shorter PFS and OS (HRs = [2.2 (1.4, 3.3), p < 0.001] and [2.8 (1.7, 4.5), p < 0.001], respectively), independently of aaIPI. In a competing risk analysis, low NKCCs at baseline were associated with a higher risk of relapse/progression (p = 0.0025), but not of death without progression (p = 0.33). Lenalidomide did not affect the prognosis value of low baseline NKCCs (p  = 0.6349). Similar results were obtained for low NKCCs at randomization. Our results demonstrate that low NKCCs at baseline and post rituximab–chemotherapy are robust prognostic factors in DLBCL and reveal that lenalidomide has no impact on this parameter. Other therapeutic strategies aiming at improving NK‐cell function could improve outcomes in DLBCL.

Publisher

Wiley

Subject

Hematology

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