Personalized risk prediction for event-free survival at 24 months in patients with diffuse large B-cell lymphoma.
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.
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Matthew J
MJ
Maurer
Department of Biostatistics, Necker Hospital, INSERM UMRS 872, AP-HP, Paris, France.
Jean-Philippe
JP
Jais
Department of Medical Oncology, Centre Léon Bérard, Lyon, France.|Centre National De La Recherche Scientifique (CNRS), Unite Mixte De Recherche (UMR), Université Claude Bernard, Lyon, France.
Hervé
H
Ghesquières
Division of Hematology, Mayo Clinic, Rochester, Minnesota.
Thomas E
TE
Witzig
Department of Biostatistics & Computational Biology, Harvard T.H. Chan, Boston, Massachusetts.
Fangxin
F
Hong
Lymphoid Malignancies Unit, Henri Mondor Hospital, Université Paris-Est, Créteil, France.
Corinne
C
Haioun
Division of Hematology, Mayo Clinic, Rochester, Minnesota.
Carrie A
CA
Thompson
Hematology, APHP, Hôpital Saint Louis, INSERM U728, IUH, Paris, France.
Catherine
C
Thieblemont
Division of Hematology, Mayo Clinic, Rochester, Minnesota.
Ivana N
IN
Micallef
Division of Hematology, Mayo Clinic, Rochester, Minnesota.
Luis F
LF
Porrata
Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France.
Vincent
V
Ribrag
Division of Hematology, Mayo Clinic, Rochester, Minnesota.
Gregorz S
GS
Nowakowski
Hopital Le Bocage, Dijon, France.
Olivier
O
Casasnovas
Department of Hematology, Centre Hospitalier Nancy-Brabois, Vandoeuvre, France.
Serge
S
Bologna
Department of Hematology, Centre Hospitalier Régional Universitaire De Lille, Lille, France.
Franck
F
Morschhauser
Department of Medicine, University of Minnesota, Minneapolis, Minnesota.|Veterans Affairs Medical Center, Minneapolis, Minnesota.
Vicki A
VA
Morrison
Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
Bruce A
BA
Peterson
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
William R
WR
Macon
INSERM Unité U955 Équipe 9, Créteil, France.
Christiane
C
Copie-Bergman
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
Andrew L
AL
Feldman
Department of Pathology, University of Iowa College of Medicine, Iowa City, Iowa.
Sergei I
SI
Syrbu
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
Paul J
PJ
Kurtin
Centre for Lymphoid Cancers, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
Randy D
RD
Gascoyne
Department of Biostatistics & Computational Biology, Harvard T.H. Chan, Boston, Massachusetts.
Hailun
H
Li
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Cristine
C
Allmer
Department of Medicine, Washington University, St. Louis, Missouri.
Brad S
BS
Kahl
Division of Hematology, Mayo Clinic, Rochester, Minnesota.
Stephen M
SM
Ansell
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Susan L
SL
Slager
Department of Pathology, University of Iowa College of Medicine, Iowa City, Iowa.
Brian K
BK
Link
Centre National De La Recherche Scientifique (CNRS), Unite Mixte De Recherche (UMR), Université Claude Bernard, Lyon, France.|Department of Hematology, Hospices Civils De Lyon, Pierre Benite, France.
Gilles
G
Salles
Division of Hematology, Mayo Clinic, Rochester, Minnesota.
Thomas M
TM
Habermann
Department of Hematology, INSERM U918, IRIB, Centre Henri Becquerel, Rouen, France.
Hervé
H
Tilly
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
James R
JR
Cerhan
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D015999:Multivariate Analysis; D057285:Precision Medicine; D011446:Prospective Studies; D012307:Risk Factors; D055815:Young Adult