title: Combination of bendamustine and rituximab as front-line therapy for patients with chronic lymphocytic leukaemia: multicenter, retrospective clinical practice experience with 279 cases outside of controlled clinical trials.
abstract: Recently, encouraging results in terms of safety and efficacy have been obtained using bendamustine-rituximab (BR) in untreated chronic lymphocytic leukaemia (CLL) patients enrolled in a phase II study. Here, we report a retrospective international multicenter study of CLL patients treated with BR as front-line therapy. The cohort included 279 patients with progressive CLL from 33 centers (29 Italian, 3 Israeli and 1 German) who received at least 1 cycle of BR as first-line treatment during the 2008-2014 period. The primary objective of this study was to evaluate the efficacy and safety of BR administered as front-line therapy, outside of controlled clinical trials. Median age was 70 years (range, 43-86 years); 62.4% were males and 35.8% had Binet stage C. Forty-two patients (15.2%) were unfit (cumulative illness rating scale [CIRS] score ≥7), and 140 (50.2%) had creatinine clearance ≤70 ml/min. Fluorescent in situ hybridisation analysis, available for 192 cases, showed that 21 (10.9%) had del11q and 18 (9.4%) del17p. The overall response rate (ORR) was 86.4%, with a complete remission rate of 28%. Patients with del17p had an ORR of 66.7%. After median follow-up of 24 months, the 2-year progression-free survival (PFS) was 69.9%; CIRS ≥7, immunoglobulin heavy-chain variable-region (IGHV) unmutated status, del17p and BR dose intensity <80% were independently associated with shorter PFS. Grade III or IV neutropenia, thrombocytopenia, and anaemia were observed in 25.9%, 15.4%, and 15.1% of patients, respectively. Twenty-four patients (8.6%) had severe infections. BR is also an effective and safe regimen for untreated CLL patients, outside of controlled clinical trials.
authors.affiliation: UOC Ematologia, Ospedale Annunziata, Cosenza, Italy. Electronic address: massim.gentile@tiscali.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Gentile
authors.affiliation: Department of Haematology and Oncology, University Medical Centre Freiburg, Freiburg, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Zirlik
authors.affiliation: University of Florence, Florence, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Ciolli
authors.affiliation: Divisione di Ematologia, Università La Sapienza, Roma, Italy.
authors.forename: Francesca R
authors.initials: FR
authors.lastname: Mauro
authors.affiliation: Unità di Ematologia, Ospedale Vito Fazzi, Lecce, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Di Renzo
authors.affiliation: Unità di Ematologia, Ospedale Vito Fazzi, Lecce, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Mastrullo
authors.affiliation: Department of Hematology, Ospedale Santo Spirito, Pescara, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Angrilli
authors.affiliation: Hematology-Oncology, Azienda Ospedaliera Pugliese-Ciaccio, Catanzaro, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Molica
authors.affiliation: Consiglio Nazionale delle Ricerche, Istituto di Fisiologia Clinica, Reggio Calabria, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tripepi
authors.affiliation: Ematologia-Azienda Ospedaliero-Universitaria, Policlinico consorziale di Bari, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Giordano
authors.affiliation: Department of Biomedical Sciences, Division of Haematology, University of Catania and Ferrarotto Hospital, Catania, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Raimondo
authors.affiliation: Hematology and Transplant Center, Department of Medicine and Surgery, University of Salerno, Salerno, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Selleri
authors.affiliation: Division of Haematology, University of Torino, A.O. Città della Salute e della Scienza di Torino, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Coscia
authors.affiliation: Hematology and Bone Marrow Transplant Unit, Dept. of Oncology, La Maddalena, Palermo, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Musso
authors.affiliation: Division of Hematology II, San Giovanni Battista Hospital, Torino, Italy.
authors.forename: Lorella
authors.initials: L
authors.lastname: Orsucci
authors.affiliation: Divisione di Ematologia, Ospedale Papardo, Messina, Italy.
authors.forename: Donato
authors.initials: D
authors.lastname: Mannina
authors.affiliation: UOC Eatologia Opedale Santa Maria Goretti, Latina, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Rago
authors.affiliation: Ospedale "A. Perrino", Brindisi, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Giannotta
authors.affiliation: Hematology Unit, Cardarelli Hospital, Naples, Italy.
authors.forename: Felicetto
authors.initials: F
authors.lastname: Ferrara
authors.affiliation: Department of Hematology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Yair
authors.initials: Y
authors.lastname: Herishanu
authors.affiliation: Hematology Institute, Kaplan Medical Center, Rehovot, Israel.
authors.forename: Lev
authors.initials: L
authors.lastname: Shvidel
authors.affiliation: Hematology Unit, Bnai-Zion Medical Center, Haifa, Israel.
authors.forename: Tamar
authors.initials: T
authors.lastname: Tadmor
authors.affiliation: Haematology Department, Ospedali Riuniti di Ancona, Ancona, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Scortechini
authors.affiliation: Hematology Unit, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Ilariucci
authors.affiliation: UO Ematologia e CTMO Ospedale Oncologico A. Businco, Cagliari, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Murru
authors.affiliation: Haematology Unit, National Cancer Research Centre Istituto Tumori, Bari, Italy.
authors.forename: Attilio
authors.initials: A
authors.lastname: Guarini
authors.affiliation: Hematology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Musuraca
authors.affiliation: Unità di Ematologia, Ospedale San Vincenzo, Taormina, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mineo
authors.affiliation: Hematology Unit, A.O. of Reggio Calabria, Italy.
authors.forename: Iolanda
authors.initials: I
authors.lastname: Vincelli
authors.affiliation: Hematology Unit, Department of Onco-Hematology, Guglielmo da Saliceto Hospital, Piacenza, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Arcari
authors.affiliation: UOC Ematologia - Ospedale Dimiccoli - Barletta, Barletta, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tarantini
authors.affiliation: Department of Haematology, ASL Caserta (CE), Hospital Moscati, Aversa, CE, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Caparrotti
authors.affiliation: Department of Biomedical Sciences, Division of Haematology, University of Catania and Ferrarotto Hospital, Catania, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Chiarenza
authors.affiliation: Department of Hematology, Ospedale Santo Spirito, Pescara, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Levato
authors.affiliation: Hematology Unit, Ospedale S. Gennaro/S. Giovanni Bosco, Napoli, Italy.
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Villa
authors.affiliation: Unità di Ematologia, Ospedale Vito Fazzi, Lecce, Italy.
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: De Paolis
authors.affiliation: Institute of Hematology, University of Bologna, Bologna, Italy.
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Zinzani
authors.affiliation: Department of Hematology, Hadassah University, Hospital and Hebrew University Medical School, Jerusalem, Israel.
authors.forename: Aaron
authors.initials: A
authors.lastname: Polliack
authors.affiliation: UOC Ematologia, Ospedale Annunziata, Cosenza, Italy. Electronic address: fortunato_morabito@tin.it.
authors.forename: Fortunato
authors.initials: F
authors.lastname: Morabito
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069461:Bendamustine Hydrochloride / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D000069283:Rituximab / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000069283:Rituximab; D000069461:Bendamustine Hydrochloride
keywords: Bendamustine; Chronic lymphocytic leukaemia; Rituximab; Therapy