title: MYC-IG rearrangements are negative predictors of survival in DLBCL patients treated with immunochemotherapy: a GELA/LYSA study.
abstract: 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.
authors.affiliation: 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;
authors.forename: Christiane
authors.initials: C
authors.lastname: Copie-Bergman
authors.affiliation: Institut Gustave Roussy, Villejuif, France;
authors.forename: Peggy
authors.initials: P
authors.lastname: Cuillière-Dartigues
authors.affiliation: INSERM, Unité 955, Creteil, France;
authors.forename: Maryse
authors.initials: M
authors.lastname: Baia
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Department of Pathology, Institut Universitaire d'Hématologie, Paris, France;
authors.forename: Josette
authors.initials: J
authors.lastname: Briere
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Necker, Department of Hematology, Paris, France;
authors.forename: Richard
authors.initials: R
authors.lastname: Delarue
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Necker, Department of Pathology, Université Paris Descartes, Paris, France;
authors.forename: Danielle
authors.initials: D
authors.lastname: Canioni
authors.affiliation: 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;
authors.forename: Gilles
authors.initials: G
authors.lastname: Salles
authors.affiliation: Centre Hospitalier Universitaire Bordeaux, Université de Bordeaux, EA2406, Bordeaux, France;
authors.forename: Marie
authors.initials: M
authors.lastname: Parrens
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Groupe Henri Mondor-Albert Chenevier, Unité Lymphoïde, Créteil, France;
authors.forename: Karim
authors.initials: K
authors.lastname: Belhadj
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, Department of Pathology, Paris, France;
authors.forename: Bettina
authors.initials: B
authors.lastname: Fabiani
authors.affiliation: Service d'Hématologie, Institut Universitaire du Cancer, Toulouse, France;
authors.forename: Christian
authors.initials: C
authors.lastname: Recher
authors.affiliation: Department of Pathology, Hôpital Maisonneuve-Rosemont, Montreal, Canada;
authors.forename: Tony
authors.initials: T
authors.lastname: Petrella
authors.affiliation: Pluridisciplinary Center for Oncology, University Hospital-Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland;
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ketterer
authors.affiliation: Centre de Lutte Contre le Cancer de Nice, Nice, France;
authors.forename: Frederic
authors.initials: F
authors.lastname: Peyrade
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Groupe Henri Mondor-Albert Chenevier, Unité Lymphoïde, Créteil, France;
authors.forename: Corinne
authors.initials: C
authors.lastname: Haioun
authors.affiliation: Institute of Human Genetics, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Kiel, Germany;
authors.forename: Inga
authors.initials: I
authors.lastname: Nagel
authors.affiliation: Institute of Human Genetics, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Kiel, Germany;
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.affiliation: Centre Henri Becquerel and INSERM Unité 918, Institut de Recherche et d'Innovation Biomédicale, Rouen, France;
authors.forename: Fabrice
authors.initials: F
authors.lastname: Jardin
authors.affiliation: 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;
authors.forename: Karen
authors.initials: K
authors.lastname: Leroy
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Necker, Department of Biostatistics, Paris, France;
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Jais
authors.affiliation: Centre Henri Becquerel and INSERM Unité 918, Institut de Recherche et d'Innovation Biomédicale, Rouen, France;
authors.forename: Herve
authors.initials: H
authors.lastname: Tilly
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Necker, Department of Pathology, Université Paris Descartes, EA 7324, Paris, France.
authors.forename: Thierry Jo
authors.initials: TJ
authors.lastname: Molina
authors.affiliation: 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;
authors.forename: Philippe
authors.initials: P
authors.lastname: Gaulard
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D000069283:Rituximab; D015996:Survival Rate; D014178:Translocation, Genetic; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007136:Immunoglobulins; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone