Rituximab in addition to LMB-based chemotherapy regimen in children and adolescents with primary mediastinal large B-cell lymphoma: results of the French LMB2001 prospective study
Marie Emilie Dourthe,
Aurélie Phulpin,
Anne Auperin,
Jacques Bosq,
Marie-Laure Couec,
Peggy Dartigues,
Stéphane Ducassou,
Nathalie Garnier,
Stéphanie Haouy,
Thierry Leblanc,
Amaury Leruste,
Catherine Paillard,
Charlotte Rigaud,
Mathieu Simonin,
Catherine Patte,
Véronique Minard-Colin
Affiliations
Marie Emilie Dourthe
Department of Pediatric Hematology and Immunology, Robert Debré University Hospital, AP-HP and University de Paris, Paris, France; Université de Paris, Institut Necker-Enfants Malades (INEM), Institut national de la santé et de la recherche médicale (Inserm) U1151, and Laboratory of Onco-Hematology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants-Malades, Paris
Aurélie Phulpin
Pediatric Oncology and Hematology Department, University Hospital of Nancy (CHRU Nancy), Nancy
Anne Auperin
Service de Biostatistique et d'Epidémiologie, Gustave Roussy Cancer Campus, INSERM U1018, CESP, Université Paris-Sud, Université Paris-Saclay, Villejuif
Jacques Bosq
Department of Biopathology, Morphology Unit, Gustave Roussy, Université Paris Saclay, Villejuif
Marie-Laure Couec
Pediatric hematology and oncology department, University Hospital of Nantes, Nantes
Peggy Dartigues
Department of Biopathology, Morphology Unit, Gustave Roussy, Université Paris Saclay, Villejuif
Stéphane Ducassou
Department of Pediatric Oncology and Haematology, University Hospital of Bordeaux, Bordeaux
Nathalie Garnier
Institut d'Hématologie et d'Oncologie Pédiatrique, Hospices Civils de Lyon, Lyon
Stéphanie Haouy
Department of Pediatric Oncology and Haematology, University Hospital of Montpellier, Montpellier
Thierry Leblanc
Université de Paris, Institut Necker-Enfants Malades (INEM), Institut national de la santé et de la recherche médicale (Inserm) U1151, and Laboratory of Onco-Hematology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants-Malades, Paris
Amaury Leruste
SIREDO Oncology Center, Institut Curie, PSL Research University, Paris
Catherine Paillard
Pediatric Hematology Oncology Department, University Hospital of Strasbourg, Strasbourg, France and INSERM UMR_S 1109
Charlotte Rigaud
Departments of Pediatric and Adolescent Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif
Mathieu Simonin
Université de Paris, Institut Necker-Enfants Malades (INEM), Institut national de la santé et de la recherche médicale (Inserm) U1151, and Laboratory of Onco-Hematology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants-Malades, Paris, France; Pediatric Hematology Oncology Department, Sorbonne Université/Trousseau Hospital, APHP, Paris
Catherine Patte
Departments of Pediatric and Adolescent Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif
Véronique Minard-Colin
Departments of Pediatric and Adolescent Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, France; INSERM Unité 1015
Primary mediastinal large B-cell lymphoma (PMLBL) is a rare entity predominantly affecting adolescents and young adults. Recently, an international phase II trial in pediatric patients using dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine and prednisone plus rituximab (DA-EPOCH-R) failed to reproduce excellent survival reported in some adult studies. The optimal therapy regimen needs to be determined in this disease. The French prospective LMB2001 trial included all patients ≤18 years with mature B-cell lymphoma treated in French centers. For patients with PMLBL, treatment included four to eight courses of Lymphomes Malins B (LMB)-based chemotherapy without radiotherapy. From 2008, rituximab was added before each chemotherapy course. From 09/2001 to 03/2012, 42 patients with PMLBL were registered. The median age was 15 years (range, 8-18). Twenty-one patients were treated with chemotherapy plus rituximab. The median follow-up was 7.1 years (interquartile range, 5.8-11.1). Five-year event-free and overall survival were 88.1% (95% confidence interval (CI): 75.0-94.8) and 95.2% (95% CI: 84.0-98.7) for the whole population. The 5-year EFS was 81.0% (95% CI: 60.0-92.3) and 95.2% (95% CI: 77.3-99.2) (hazard ratio =0.24; 95% CI: 0.03- 2.2) and 5-year overall survival was 90.5% (95% CI: 71.1-97.3) and 100% for patients treated without and with rituximab, respectively. Only one of 21 patients treated with rituximab and LMB-based chemotherapy had local early treatment failure but achieved prolonged complete remission with second-line chemotherapy and radiotherapy. Intensive LMBbased chemotherapy with rituximab achieved excellent survival in children/adolescents with PMLBL. Further international prospective studies are required to confirm these results in this population.
