Page 154 - Haematologica-April 2018

Correspondence:
veronique.leblond@aphp.fr
Received: August 2, 2017. Accepted: January 22, 2018. Pre-published: February 1, 2018.
doi:10.3324/haematol.2017.170480
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Ferrata Storti Foundation
Chronic Lymphoblastic Leukemia
Rituximab plus bendamustine or chlorambucil for chronic lymphocytic leukemia: primary analysis of the randomized, open-label MABLE study
Anne-Sophie Michallet,1 Melih Aktan,2 Wolfgang Hiddemann,3 Osman Ilhan,4 Peter Johansson,5 Kamel Laribi,6 Balkis Meddeb,7 Carol Moreno,8
João Raposo,9 Anna Schuh,10 Ali Ünal,11 Tom Widenius,12 Alf Bernhardt,13 Kerstin Kellershohn,14 Dimitri Messeri,13 Stuart Osborne13 and Véronique Leblond15
1Department of Hematology, CLCC Centre Léon Bérard, Lyon, France; 2Istanbul Medical Faculty, Istanbul University, Turkey; 3Department of Internal Medicine III, Ludwig- Maximilians University of Munich, Germany; 4Department of Hematology, Ankara University School of Medicine, Turkey; 5Department of Hematology, Uddevalla Hospital, Sweden; 6Department of Hematology, Centre Hospitalier du Mans, Le Mans, France; 7Hematology Department, Aziza Othmana University Hospital, Tunis, Tunisia; 8Department of Hematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 9Hematology Service, Hospital de Santa Maria, Lisbon, Portugal; 10Department of Oncology, Oxford University Hospitals, UK; 11Department of Hematology, Erciyes University Medical School, Kayseri, Turkey; 12Department of Internal Medicine, Peijas Hospital, Vantaa, Finland; 13Product Development Medical Affairs, F. Hoffmann-La Roche Ltd., Basel, Switzerland; 14Medical Affairs, Roche Pharma AG, Grenzach-Wyhlen, Germany and 15Clinical Hematology, AP-HP Hôpital Pitié-Salpêtrière, UPMC University, Paris, France
ABSTRACT
MABLE investigated the efficacy and safety of rituximab plus ben- damustine or rituximab plus chlorambucil in fludarabine-ineli- gible patients with chronic lymphocytic leukemia. Patients received rituximab plus bendamustine or rituximab plus chlorambucil every four weeks for six cycles. Rituximab plus chlorambucil-treated patients without a complete response after Cycle 6 received chlorambu- cil monotherapy for at least six additional cycles or until complete response. The primary endpoint was complete response rate (confirmed by bone marrow biopsy) after Cycle 6 in first-line patients. Secondary endpoints included progression-free survival, overall survival, minimal residual disease, and safety. Overall, 357 patients were randomized (rit- uximab plus bendamustine, n=178; rituximab plus chlorambucil, n=179; intent-to-treat population), including 241 first-line patients (n=121 and n=120, respectively); 355 patients received treatment (n=177 and n=178, respectively; safety population). In first-line patients, complete response rate after Cycle 6 (rituximab plus bendamustine, 24%; rituximab plus chlorambucil, 9%; P=0.002) and median progression-free survival (ritux- imab plus bendamustine, 40 months; rituximab plus chlorambucil, 30 months; P=0.003) were higher with rituximab plus bendamustine than rituximab plus chlorambucil. Overall response rate and overall sur- vival were not different. In first-line patients with a complete response, minimal residual disease-negativity was higher with rituximab plus ben- damustine than rituximab plus chlorambucil (66% vs. 36%). Overall adverse event incidence was similar (rituximab plus bendamustine, 98%; rituximab plus chlorambucil, 97%). Rituximab plus bendamustine may be a valuable first-line option for fludarabine-ineligible patients with chronic lymphocytic leukemia. clinicaltrials.gov identifier: 01056510
Introduction
Rituximab plus fludarabine and cyclophosphamide (R-FC) is standard treatment for medically fit chronic lymphocytic leukemia (CLL) patients,1,2 with high response rates in previously untreated patients (first-line; 1L) and treated patients (second- line; 2L).3-5 However, many CLL patients are elderly and have comorbidities, mak- ing them ineligible for fludarabine-based treatment.6 Chemotherapy options for these patients include bendamustine (B) and chlorambucil (Clb).
Haematologica 2018 Volume 103(4):698-706
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