Molecular remission is an independent predictor of clinical outcome in patients with mantle cell lymphoma after combined immunochemotherapy: a European MCL intergroup study

Author:

Pott Christiane1,Hoster Eva2,Delfau-Larue Marie-Helene3,Beldjord Kheira4,Böttcher Sebastian1,Asnafi Vahid4,Plonquet Anne3,Siebert Reiner5,Callet-Bauchu Evelyne6,Andersen Niels7,van Dongen Jacques J. M.8,Klapper Wolfram9,Berger Françoise10,Ribrag Vincent11,van Hoof Achiel L.12,Trneny Marek13,Walewski Jan14,Dreger Peter15,Unterhalt Michael2,Hiddemann Wolfgang2,Kneba Michael1,Kluin-Nelemans Hanneke C.16,Hermine Olivier17,Macintyre Elizabeth4,Dreyling Martin2

Affiliation:

1. Second Medical Department, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany;

2. Department of Internal Medicine III, University of Munich, Grosshadern, Germany;

3. Assistance Publique-Hopitaux de Paris, Hôpital Henri-Mondor, Immunology Department, Inserm U955, Equipe 9, Université Paris XII, Créteil, France, for the Groupe d'Etudes de Lymphomes de L'Adulte (GELA);

4. Laboratoire d'Hématologie, Hôpital Necker-Enfants-Malades, Paris, France, for the GELA;

5. Institute of Human Genetics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany;

6. Service d'Hématologie Biologique, Centre Hospitalier Lyon Sud, Pierre-Bénite, France;

7. Department of Hematology, Rigshospitalet, Copenhagen, Denmark;

8. Department of Immunology, Erasmus MC, Rotterdam, The Netherlands;

9. Institute of Hematopathology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany;

10. Department of Pathology, Centre Hospitalier Lyon-Sud, Lyon, France;

11. Laboratoire de Récherche Translationelle, Institut Gustave Roussy, Villejuif, France;

12. Department of Hematology, University Hospital St Jan, Brugge, Belgium;

13. First Department of Medicine, Charles University, Prague, Czech Republic;

14. Institute of Oncology, Maria Sklodowska-Curie Memorial Cancer Center, Warszawa, Poland;

15. Department of Medicine V, University of Heidelberg, Heidelberg, Germany;

16. Department of Hematology, University Medical Center, University of Groningen, Groningen, The Netherlands; and

17. Department of Clinical Hematology, University Paris Descartes, Centre National de la Recherche Scientifique Unite Mixte de Recherche 8147, Necker Hospital Paris, France, for the GELA

Abstract

AbstractThe prognostic impact of minimal residual disease (MRD) was analyzed in 259 patients with mantle cell lymphoma (MCL) treated within 2 randomized trials of the European MCL Network (MCL Younger and MCL Elderly trial). After rituximab-based induction treatment, 106 of 190 evaluable patients (56%) achieved a molecular remission (MR) based on blood and/or bone marrow (BM) analysis. MR resulted in a significantly improved response duration (RD; 87% vs 61% patients in remission at 2 years, P = .004) and emerged to be an independent prognostic factor for RD (hazard ratio = 0.4, 95% confidence interval, 0.1-0.9, P = .028). MR was highly predictive for prolonged RD independent of clinical response (complete response [CR], complete response unconfirmed [CRu], partial response [PR]; RD at 2 years: 94% in BM MRD-negative CR/CRu and 100% in BM MRD-negative PR, compared with 71% in BM MRD-positive CR/CRu and 51% in BM MRD-positive PR, P = .002). Sustained MR during the postinduction period was predictive for outcome in MCL Younger after autologous stem cell transplantation (ASCT; RD at 2 years 100% vs 65%, P = .001) and during maintenance in MCL Elderly (RD at 2 years: 76% vs 36%, P = .015). ASCT increased the proportion of patients in MR from 55% before high-dose therapy to 72% thereafter. Sequential MRD monitoring is a powerful predictor for treatment outcome in MCL. These trials are registered at www.clinicaltrials.gov as #NCT00209222 and #NCT00209209.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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