Personalized risk prediction for event‐free survival at 24 months in patients with diffuse large B‐cell lymphoma |
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| Authors: | Matthew J. Maurer Jean‐Philippe Jais Hervé Ghesquières Thomas E. Witzig Fangxin Hong Corinne Haioun Carrie A. Thompson Catherine Thieblemont Ivana N. Micallef Luis F. Porrata Vincent Ribrag Gregorz S. Nowakowski Olivier Casasnovas Serge Bologna Franck Morschhauser Vicki A. Morrison Bruce A. Peterson William R. Macon Christiane Copie‐Bergman Andrew L. Feldman Sergei I. Syrbu Paul J. Kurtin Randy D. Gascoyne Hailun Li Cristine Allmer Brad S. Kahl Stephen M. Ansell Susan L. Slager Brian K. Link Gilles Salles Thomas M. Habermann James R. Cerhan |
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| Affiliation: | 1. Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota;2. Department of Biostatistics, Necker Hospital, INSERM UMRS 872, AP‐HP, Paris, France;3. Department of Medical Oncology, Centre Léon Bérard, Lyon, France;4. Centre National De La Recherche Scientifique (CNRS), Unite Mixte De Recherche (UMR), Université Claude Bernard, Lyon, France;5. Division of Hematology, Mayo Clinic, Rochester, Minnesota;6. Department of Biostatistics & Computational Biology, Harvard T.H. Chan, Boston, Massachusetts;7. Lymphoid Malignancies Unit, Henri Mondor Hospital, Université Paris‐Est, Créteil, France;8. Hematology, APHP, H?pital Saint Louis, INSERM U728, IUH, Paris, France;9. Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France;10. Hopital Le Bocage, Dijon, France;11. Department of Hematology, Centre Hospitalier Nancy‐Brabois, France;12. Department of Hematology, Centre Hospitalier Régional Universitaire De Lille, Lille, France;13. Department of Medicine, University of Minnesota, Minneapolis, Minnesota;14. Veterans Affairs Medical Center, Minneapolis, Minnesota;15. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota;16. INSERM Unité U955 équipe 9, Créteil, France;17. Department of Pathology, University of Iowa College of Medicine, Iowa City, Iowa;18. Centre for Lymphoid Cancers, British Columbia Cancer Agency, Vancouver, British Columbia, Canada;19. Department of Medicine, Washington University, St. Louis, Missouri;20. Department of Hematology, Hospices Civils De Lyon, Pierre Benite, France |
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| Abstract: | We recently defined event‐free survival at 24 months (EFS24) as a clinically relevant outcome for patients with DLBCL. Patients who fail EFS24 have very poor overall survival, while those who achieve EFS24 have a subsequent overall survival equivalent to that of the age‐ and sex‐matched general population. Here, we develop and validate a clinical risk calculator (IPI24) for EFS24. Model building was performed on a discovery dataset of 1,348 patients with DLBCL and treated with anthracycline‐based immunochemotherapy. A multivariable model containing age, Ann Arbor stage, normalized serum LDH, ALC, ECOG performance status, bulky disease, and sex was identified. The model was then applied to an independent validation dataset of 1,177 DLBCL patients. The IPI24 score estimates the probability of failing to achieve the EFS24 endpoint for an individual patient. The IPI24 model showed superior discriminatory ability (c‐statistic = 0.671) in the validation dataset compared to the IPI (c‐statistic = 0.649) or the NCCN‐IPI (c‐statistic = 0.657). After recalibration of the model on the combined dataset, the median predicted probability of failing to achieve EFS24 was 36% (range, 12–88%), and the IPI24 showed an EFS24 gradient in all IPI groups. The IPI24 also identified a significant percentage of patients with high risk disease, with over 20% of patients having a 50% or higher risk of failing to achieve EFS24. The IPI24 provides an individual patient level probability of achieving the clinically relevant EFS24 endpoint. It can be used via electronic apps. Am. J. Hematol. 91:179–184, 2016. © 2015 Wiley Periodicals, Inc. |
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