G A Amos Burke1, Veronique Minard-Colin2, Anne Aupérin3, Sarah Alexander4, Marta Pillon5, Rafael Delgado6, József Zsíros7, Anne Uyttebroeck8, Peggy Dartigues9, Rodney R Miles10, Bernarda Kazanowska11, Alan K Chiang12, Stéphanie Haouy13, Catherine M Bollard14, Monika Csoka15, Keith Wheatley16, Donald A Barkauskas17, Peter C Adamson18, Gilles Vassal19, Catherine Patte2, Thomas G Gross20. 1. Department of Paediatric Haematology, Oncology and Palliative Care, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, United Kingdom. 2. Department of Pediatric and Adolescent Oncology, INSERM 1015, Gustave Roussy, Université Paris-Saclay, Villejuif, France. 3. Unit of Biostatistics and Epidemiology, Gustave Roussy, Oncostat 1018 INSERM, Labeled Ligue Contre le Cancer, Université Paris-Saclay, Villejuif, France. 4. Division of Haematology/Oncology, Hospital for Sick Children, Toronto, ON, Canada. 5. Pediatric Hematology and Oncology, University of Padova, Padova, Italy. 6. Pediatric Hematology and Oncology, University of Valencia, Valencia, Spain. 7. Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands. 8. Department of Pediatric Hematology and Oncology, University Hospitals Leuven, Leuven, Belgium. 9. Department of Biopathology, Gustave Roussy, Université Paris-Saclay, Villejuif, France. 10. Department of Pathology and ARUP Laboratories and Huntsman Cancer Institute, Salt Lake City, UT. 11. Department of Pediatric Bone Marrow Transplantation, Oncology, and Hematology, Wroclaw Medical University, Wroclaw, Poland. 12. Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, Queen Mary Hospital, The University of Hong Kong, Pok Fu Lam, Hong Kong. 13. Department of Paediatric Haematology, Oncology, CHU Arnaud de Villeneuve, Montpellier, France. 14. Center for Cancer and Immunology Research, Children's National Health System and The George Washington University, Washington, DC. 15. Pediatric Hematology and Oncology, Semmelweis University, Budapest, Hungary. 16. Cancer Research UK Clinical Trials Unit, Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom. 17. Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA. 18. Oncology Development & Pediatric Innovation, Sanofi, Cambridge, MA. 19. Department of Clinical Research, Gustave Roussy, Université Paris-Saclay, Villejuif, France. 20. Department of Pediatrics, Center for Cancer and Blood Diseases, Children's Hospital Colorado, Aurora, CO.
Abstract
PURPOSE: A dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine and prednisone plus rituximab (DA-EPOCH-R) regimen has been shown to deliver excellent survival for adults with primary mediastinal large B-cell lymphoma (PMLBL) without the use of radiotherapy. No international prospective evaluation of this regimen has previously been reported in children and adolescents. PATIENTS AND METHODS: We conducted an international single-arm phase II trial involving patients younger than age 18 years with PMLBL who were to receive six courses of DA-EPOCH-R. The primary end point was event-free survival (EFS). Overall survival and toxicity were also assessed. This trial was registered (ClinicalTrials.gov identifier: NCT01516567). RESULTS: Analyses were based on 46 patients. The median age was 15.4 years (interquartile range: 14-16 years). The median follow-up was 59.0 months (interquartile range: 52.6-69.2 months). Fourteen events were observed (eight relapses or progressions (including three parenchymal CNS relapses), four residual lymphoma, and two second malignancies). The 4-year EFS was 69.6% (95% CI, 55.2 to 80.9), which did not differ from the rate observed historically (P = .59). Seven deaths occurred (six disease-related and one second malignancy). The overall survival was 84.8% (95% CI, 71.8 to 92.4). Twenty-two patients (48%) reached dose levels ≥ 4. Nonhematologic adverse events grade ≥ 3 or cardiac adverse events grade ≥ 2 occurred in 47 of 276 (17%) courses and 30 of 46 patients (65%). CONCLUSION: DA-EPOCH-R did not improve the EFS compared with a historical control in this first prospective multisite international study of children and adolescents with PMLBL. Further studies are required to determine the optimum therapy for children and adolescents with this lymphoma.
PURPOSE: A dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine and prednisone plus rituximab (DA-EPOCH-R) regimen has been shown to deliver excellent survival for adults with primary mediastinal large B-cell lymphoma (PMLBL) without the use of radiotherapy. No international prospective evaluation of this regimen has previously been reported in children and adolescents. PATIENTS AND METHODS: We conducted an international single-arm phase II trial involving patients younger than age 18 years with PMLBL who were to receive six courses of DA-EPOCH-R. The primary end point was event-free survival (EFS). Overall survival and toxicity were also assessed. This trial was registered (ClinicalTrials.gov identifier: NCT01516567). RESULTS: Analyses were based on 46 patients. The median age was 15.4 years (interquartile range: 14-16 years). The median follow-up was 59.0 months (interquartile range: 52.6-69.2 months). Fourteen events were observed (eight relapses or progressions (including three parenchymal CNS relapses), four residual lymphoma, and two second malignancies). The 4-year EFS was 69.6% (95% CI, 55.2 to 80.9), which did not differ from the rate observed historically (P = .59). Seven deaths occurred (six disease-related and one second malignancy). The overall survival was 84.8% (95% CI, 71.8 to 92.4). Twenty-two patients (48%) reached dose levels ≥ 4. Nonhematologic adverse events grade ≥ 3 or cardiac adverse events grade ≥ 2 occurred in 47 of 276 (17%) courses and 30 of 46 patients (65%). CONCLUSION: DA-EPOCH-R did not improve the EFS compared with a historical control in this first prospective multisite international study of children and adolescents with PMLBL. Further studies are required to determine the optimum therapy for children and adolescents with this lymphoma.
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