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MYC-IG rearrangements are negative predictors of survival in DLBCL patients treated with immunochemotherapy: a GELA/LYSA study.

  • Copie-Bergman C Assistance Publique-Hôpitaux de Paris, Groupe Henri Mondor-Albert Chenevier, Département de Pathologie, Creteil, France; Universite Paris-Est, Faculté de Médecine, Unité Mixte de Recherche Scientifique 955, Créteil, France; INSERM, Unité 955, Creteil, France;
  • Cuillière-Dartigues P Institut Gustave Roussy, Villejuif, France;
  • Baia M INSERM, Unité 955, Creteil, France;
  • Briere J Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Department of Pathology, Institut Universitaire d'Hématologie, Paris, France;
  • Delarue R Assistance Publique-Hôpitaux de Paris, Hôpital Necker, Department of Hematology, Paris, France;
  • Canioni D Assistance Publique-Hôpitaux de Paris, Hôpital Necker, Department of Pathology, Université Paris Descartes, Paris, France;
  • Salles G Hospices Civils de Lyon, Université Claude Bernard Lyon-1, Service d'Hématologie, Unité Mixte de Recherche 5239, Centre National de la Recherche Scientifique, Lyon, France;
  • Parrens M Centre Hospitalier Universitaire Bordeaux, Université de Bordeaux, EA2406, Bordeaux, France;
  • Belhadj K Assistance Publique-Hôpitaux de Paris, Groupe Henri Mondor-Albert Chenevier, Unité Lymphoïde, Créteil, France;
  • Fabiani B Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, Department of Pathology, Paris, France;
  • Recher C Service d'Hématologie, Institut Universitaire du Cancer, Toulouse, France;
  • Petrella T Department of Pathology, Hôpital Maisonneuve-Rosemont, Montreal, Canada;
  • Ketterer N Pluridisciplinary Center for Oncology, University Hospital-Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland;
  • Peyrade F Centre de Lutte Contre le Cancer de Nice, Nice, France;
  • Haioun C Assistance Publique-Hôpitaux de Paris, Groupe Henri Mondor-Albert Chenevier, Unité Lymphoïde, Créteil, France;
  • Nagel I Institute of Human Genetics, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Kiel, Germany;
  • Siebert R Institute of Human Genetics, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Kiel, Germany;
  • Jardin F Centre Henri Becquerel and INSERM Unité 918, Institut de Recherche et d'Innovation Biomédicale, Rouen, France;
  • Leroy K Assistance Publique-Hôpitaux de Paris, Groupe Henri Mondor-Albert Chenevier, Département de Pathologie, Creteil, France; Universite Paris-Est, Faculté de Médecine, Unité Mixte de Recherche Scientifique 955, Créteil, France; INSERM, Unité 955, Creteil, France;
  • Jais JP Assistance Publique-Hôpitaux de Paris, Hôpital Necker, Department of Biostatistics, Paris, France;
  • Tilly H Centre Henri Becquerel and INSERM Unité 918, Institut de Recherche et d'Innovation Biomédicale, Rouen, France;
  • Molina TJ Assistance Publique-Hôpitaux de Paris, Hôpital Necker, Department of Pathology, Université Paris Descartes, EA 7324, Paris, France.
  • Gaulard P Assistance Publique-Hôpitaux de Paris, Groupe Henri Mondor-Albert Chenevier, Département de Pathologie, Creteil, France; Universite Paris-Est, Faculté de Médecine, Unité Mixte de Recherche Scientifique 955, Créteil, France; INSERM, Unité 955, Creteil, France;
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  • 2015-09-17
Published in:
  • Blood. - 2015
Adolescent
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Murine-Derived
Antineoplastic Combined Chemotherapy Protocols
Cyclophosphamide
Disease-Free Survival
Doxorubicin
Female
Gene Rearrangement
Humans
Immunoglobulins
Lymphoma, Large B-Cell, Diffuse
Male
Middle Aged
Prednisone
Proto-Oncogene Proteins c-myc
Rituximab
Survival Rate
Translocation, Genetic
Vincristine
English Diffuse large B-cell lymphoma (DLBCL) with MYC rearrangement (MYC-R) carries an unfavorable outcome. We explored the prognostic value of the MYC translocation partner gene in a series of MYC-R de novo DLBCL patients enrolled in first-line prospective clinical trials (Groupe d'Etudes des Lymphomes de l'Adulte/Lymphoma Study Association) and treated with rituximab-anthracycline-based chemotherapy. A total of 774 DLBCL cases characterized for cell of origin by the Hans classifier were analyzed using fluorescence in situ hybridization with BCL2, BCL6, MYC, immunoglobulin (IG)K, and IGL break-apart and IGH/MYC, IGK/MYC, and IGL/MYC fusion probes. MYC-R was observed in 51/574 (8.9%) evaluable DLBCL cases. MYC-R cases were predominantly of the germinal center B-cell-like subtype 37/51 (74%) with no distinctive morphologic and phenotypic features. Nineteen cases were MYC single-hit and 32 cases were MYC double-hit (MYC plus BCL2 and/or BCL6) DLBCL. MYC translocation partner was an IG gene in 24 cases (MYC-IG) and a non-IG gene (MYC-non-IG) in 26 of 50 evaluable cases. Noteworthy, MYC-IG patients had shorter overall survival (OS) (P = .0002) compared with MYC-negative patients, whereas no survival difference was observed between MYC-non-IG and MYC-negative patients. In multivariate analyses, MYC-IG predicted poor progression-free survival (P = .0051) and OS (P = .0006) independently from the International Prognostic Index and the Hans classifier. In conclusion, we show in this prospective randomized trial that the adverse prognostic impact of MYC-R is correlated to the MYC-IG translocation partner gene in DLBCL patients treated with immunochemotherapy. These results may have an important impact on the clinical management of DLBCL patients with MYC-R who should be routinely characterized according to MYC partner gene. These trials are individually registered at www.clinicaltrials.gov as #NCT00144807, #NCT01087424, #NCT00169143, #NCT00144755, #NCT00140660, #NCT00140595, and #NCT00135499.
Language
  • English
Open access status
bronze
Identifiers
Persistent URL
https://sonar.ch/global/documents/77975
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