title: Fludarabine, cyclophosphamide and lenalidomide in patients with relapsed/refractory chronic lymphocytic leukemia. A multicenter phase I-II GIMEMA trial.
abstract: The activity and safety of a regimen combining lenalidomide with fludarabine and cyclophosphamide (FC) was investigated in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Treatment consisted of six monthly courses of the FC regimen combined with 14 days of lenalidomide given at the starting dose of 2.5 mg during course 1. The maximum tolerated dose of lenalidomide was 5 mg. Forty patients were assessed for response, 66% were IGHV unmutated, 45% showed deletion 11q or 17p. The overall response and complete remission rates were 62.5% and 22.5%, respectively, the median progression-free and overall survival (OS) were 19 and 45 months, respectively. Grade 3-4 granulocytopenia was observed in 65% of cases, severe infections in 7.5%, the lenalidomide-related toxicity was mild. In conclusion, the results of this study demonstrate that low-dose lenalidomide associated with the FC schedule is an effective treatment for R/R patients with CLL, associated with an acceptable safety profile.
authors.affiliation: a Department of Cellular Biotechnologies and Hematology, Hematology , Sapienza University , Rome , Italy.
authors.forename: Francesca R
authors.initials: FR
authors.lastname: Mauro
authors.affiliation: b U.O.C. Ematologia 1 , IRCCS San Martino-IST , Genoa , Italy.
authors.forename: Angelo M
authors.initials: AM
authors.lastname: Carella
authors.affiliation: c Azienda Ospedaliera Pugliese Ciaccio , Catanzaro , Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Molica
authors.affiliation: d GIMEMA Foundation , Rome , Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Paoloni
authors.affiliation: e Department of Oncohematology , University of Perugia, Santa Maria Hospital , Terni , Italy.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Liberati
authors.affiliation: f Division of Oncology-Hematology , Nocera-Pagani Hospital , Nocera Inferiore , Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Zaja
authors.affiliation: g Hematology-BMT Unit , S. Maria Misericordia Hospital, University of Udine , Udine , Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Belsito
authors.affiliation: h Hematology-BMT Unit , IRCCS Ca'Granda Ospedale Maggiore, Policlinico Foundation , Milan , Italy.
authors.forename: Agostino
authors.initials: A
authors.lastname: Cortellezzi
authors.affiliation: i U.O. Ematologia con Trapianto , Università degli Studi Aldo Moro , Bari , Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Rizzi
authors.affiliation: j Department of Oncology and Hematology, Hematology Unit , Rimini , Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Tosi
authors.affiliation: b U.O.C. Ematologia 1 , IRCCS San Martino-IST , Genoa , Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Spriano
authors.affiliation: a Department of Cellular Biotechnologies and Hematology, Hematology , Sapienza University , Rome , Italy.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Ferretti
authors.affiliation: a Department of Cellular Biotechnologies and Hematology, Hematology , Sapienza University , Rome , Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Nanni
authors.affiliation: a Department of Cellular Biotechnologies and Hematology, Hematology , Sapienza University , Rome , Italy.
authors.forename: Marilisa
authors.initials: M
authors.lastname: Marinelli
authors.affiliation: a Department of Cellular Biotechnologies and Hematology, Hematology , Sapienza University , Rome , Italy.
authors.forename: Maria S
authors.initials: MS
authors.lastname: De Propris
authors.affiliation: d GIMEMA Foundation , Rome , Italy.
authors.forename: Sonia M
authors.initials: SM
authors.lastname: Orlando
authors.affiliation: d GIMEMA Foundation , Rome , Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Vignetti
authors.affiliation: k Department of Hematology , Arcispedale Sant'Anna , Ferrara , Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cuneo
authors.affiliation: a Department of Cellular Biotechnologies and Hematology, Hematology , Sapienza University , Rome , Italy.|l Department of Molecular Medicine , Sapienza University , Rome , Italy.
authors.forename: Anna R
authors.initials: AR
authors.lastname: Guarini
authors.affiliation: a Department of Cellular Biotechnologies and Hematology, Hematology , Sapienza University , Rome , Italy.
authors.forename: Robin
authors.initials: R
authors.lastname: Foà
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002423:Cause of Death; D003520:Cyclophosphamide / Q000008:administration & dosage; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D012008:Recurrence; D012074:Remission Induction; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D013792:Thalidomide; D003520:Cyclophosphamide; D000077269:Lenalidomide; D014740:Vidarabine; C024352:fludarabine
keywords: Chronic lymphocytic leukemia; cyclophosphamide; fludarabine; lenalidomide; refractory; relapsed