Molecular prediction of durable remission after first-line fludarabine-cyclophosphamide-rituximab in chronic lymphocytic leukemia.
Fludarabine, cyclophosphamide, and rituximab (FCR) has represented a significant treatment advancement in chronic lymphocytic leukemia (CLL). In the new scenario of targeted agents, there is an increasing interest in identifying patients who gain the maximum benefit from FCR. In this observational multicenter retrospective analysis of 404 CLL patients receiving frontline FCR, the combination of three biomarkers that are widely tested before treatment (IGHV mutation status, 11q deletion and 17p deletion; available in 80% of the study cohort) allowed to identify a very low-risk category of patients carrying mutated IGHV genes but neither 11q or 17p deletion that accounted for 28% of all cases. The majority of very low-risk patients (71%) remained free of progression after treatment and their hazard of relapse decreased after 4 years from FCR. The life expectancy of very low-risk patients (91% at 5 years) was superimposable to that observed in the matched normal general population, indicating that neither the disease nor complications of its treatment affected survival in this favorable CLL group. These findings need a prospective validation and may be helpful for the design of clinical trials aimed at comparing FCR to new targeted treatments of CLL, and, possibly, for optimized disease management.
Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy;
Davide
D
Rossi
Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy;
Lodovico
L
Terzi-di-Bergamo
Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy;
Lorenzo
L
De Paoli
Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy;
Michaela
M
Cerri
Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy;
Guido
G
Ghilardi
Hematology, Department of Clinical and Molecular Biomedicine, University of Catania, Catania, Italy;
Annalisa
A
Chiarenza
Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Aviano, Italy;
Pietro
P
Bulian
Department of Cell Therapy and Hematology, Ospedale San Bortolo, Vicenza, Italy;
Carlo
C
Visco
Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy;
Francesca R
FR
Mauro
Hematology Unit, Department of Onco-Hematology, Hospital of Cosenza, Cosenza, Italy;
Fortunato
F
Morabito
Department of Hematology Oncology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico and University of Milan, Milan, Italy;
Agostino
A
Cortelezzi
Clinica Ematologica, Centro Trapianti e Terapie Cellulari "Carlo Melzi" Department of Experimental and Clinical Medical Sciences (DISM), Azienda Ospedaliera Universitaria S. Maria Misericordia, Udine, Italy;
Francesco
F
Zaja
Cancer Sciences Unit, Southampton Cancer Research UK and National Institute for Health Research Experimental Cancer Medicine Centre, University of Southampton, Southampton, United Kingdom; Division of Hematology, University of Siena, Siena, Italy;
Francesco
F
Forconi
Institute of Hematology, Catholic University of the Sacred Heart, Rome, Italy;
Luca
L
Laurenti
Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy;
Ilaria
I
Del Giudice
Hematology Unit, Department of Onco-Hematology, Hospital of Cosenza, Cosenza, Italy;
Massimo
M
Gentile
Hematology Unit, Hospital of Reggio Calabria, Reggio Calabria, Italy;
Iolanda
I
Vincelli
Department of Hematology, Spedali Civili, Brescia, Italy;
Marina
M
Motta
Division of Hematology, Azienda Ospedaliero Universitaria Città della Salute e della Scienza and University of Turin, Turin, Italy;
Marta
M
Coscia
Hematology Section, Azienda Ospedaliero Universitaria Arcispedale S. Anna, University of Ferrara, Ferrara, Italy;
Gian Matteo
GM
Rigolin
Department of Oncology/Haematology, Niguarda Cancer Center, Niguarda Ca Granda Hospital, Milan, Italy;
Alessandra
A
Tedeschi
Department of Clinical Sciences and Community Health, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico and University of Milan, Milan, Italy;
Antonino
A
Neri
Division of Hematology, Department of Oncology and Hematology, University of Modena and Reggio Emilia, Modena, Italy;
Roberto
R
Marasca
Section of Hematology, Department of Medicine, University of Verona, Verona, Italy;
Omar
O
Perbellini
Department of Hematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain;
Carol
C
Moreno
Department of Hematology, Tor Vergata University, Rome, Italy;
Giovanni
G
Del Poeta
Hematology and Cell Therapy Unit, Ospedale Mauriziano and University of Turin, Turin, Italy; and.
Massimo
M
Massaia
Institute of Hematology 'L. e A. Seràgnoli', University of Bologna, Bologna, Italy.
Pier Luigi
PL
Zinzani
Department of Oncology/Haematology, Niguarda Cancer Center, Niguarda Ca Granda Hospital, Milan, Italy;
Marco
M
Montillo
Hematology Section, Azienda Ospedaliero Universitaria Arcispedale S. Anna, University of Ferrara, Ferrara, Italy;
Antonio
A
Cuneo
Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Aviano, Italy;
Valter
V
Gattei
Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy;
Robin
R
Foà
Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy;
Gianluca
G
Gaidano
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D000069283:Rituximab / Q000008:administration & dosage; D058496:Smith-Magenis Syndrome; D015996:Survival Rate; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
D000069283:Rituximab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine