title: Bendamustine combined with rituximab in patients with relapsed and/or refractory chronic lymphocytic leukemia: a multicenter phase II trial of the German Chronic Lymphocytic Leukemia Study Group.
abstract: OBJECTIVE
  The objective of this trial was to evaluate safety and efficacy of bendamustine combined with rituximab (BR) in patients with relapsed and/or refractory chronic lymphocytic leukemia (CLL).
  
  
  METHODS
  Seventy-eight patients, including 22 patients with fludarabine-refractory disease (28.2%) and 14 patients (17.9%) with deletion of 17p, received BR chemoimmunotherapy. Bendamustine was administered at a dose of 70 mg/m(2) on days 1 and 2 combined with rituximab 375 mg/m(2) on day 0 of the first course and 500 mg/m(2) on day 1 during subsequent courses for up to six courses.
  
  
  RESULTS
  On the basis of intent-to-treat analysis, the overall response rate was 59.0% (95% CI, 47.3% to 70.0%). Complete response, partial response, and nodular partial response were achieved in 9.0%, 47.4%, and 2.6% of patients, respectively. Overall response rate was 45.5% in fludarabine-refractory patients and 60.5% in fludarabine-sensitive patients. Among genetic subgroups, 92.3% of patients with del(11q), 100% with trisomy 12, 7.1% with del(17p), and 58.7% with unmutated IGHV status responded to treatment. After a median follow-up time of 24 months, the median event-free survival was 14.7 months. Severe infections occurred in 12.8% of patients. Grade 3 or 4 neutropenia, thrombocytopenia, and anemia were documented in 23.1%, 28.2%, and 16.6% of patients, respectively.
  
  
  CONCLUSIONS
  Chemoimmunotherapy with BR is effective and safe in patients with relapsed CLL and has notable activity in fludarabine-refractory disease. Major but tolerable toxicities were myelosuppression and infections. These promising results encouraged us to initiate a further phase II trial evaluating the BR regimen in patients with previously untreated CLL.
authors.affiliation: Department I of Internal Medicine, University of Cologne, Kerpener Str 62, 50937 Köln, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Fischer
authors.forename: Paula
authors.initials: P
authors.lastname: Cramer
authors.forename: Raymonde
authors.initials: R
authors.lastname: Busch
authors.forename: Stephan
authors.initials: S
authors.lastname: Stilgenbauer
authors.forename: Jasmin
authors.initials: J
authors.lastname: Bahlo
authors.forename: Carmen D
authors.initials: CD
authors.lastname: Schweighofer
authors.forename: Sebastian
authors.initials: S
authors.lastname: Böttcher
authors.forename: Peter
authors.initials: P
authors.lastname: Staib
authors.forename: Michael
authors.initials: M
authors.lastname: Kiehl
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Eckart
authors.forename: Gabriele
authors.initials: G
authors.lastname: Kranz
authors.forename: Valentin
authors.initials: V
authors.lastname: Goede
authors.forename: Thomas
authors.initials: T
authors.lastname: Elter
authors.forename: Andreas
authors.initials: A
authors.lastname: Bühler
authors.forename: Dirk
authors.initials: D
authors.lastname: Winkler
authors.forename: Michael
authors.initials: M
authors.lastname: Kneba
authors.forename: Hartmut
authors.initials: H
authors.lastname: Döhner
authors.forename: Barbara F
authors.initials: BF
authors.lastname: Eichhorst
authors.forename: Michael
authors.initials: M
authors.lastname: Hallek
authors.forename: Clemens-Martin
authors.initials: CM
authors.lastname: Wendtner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069461:Bendamustine Hydrochloride; D019008:Drug Resistance, Neoplasm; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D009588:Nitrogen Mustard Compounds / Q000008:administration & dosage / Q000009:adverse effects; D011446:Prospective Studies; D012008:Recurrence; D000069283:Rituximab; D016019:Survival Analysis; D014740:Vidarabine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D009588:Nitrogen Mustard Compounds; D000069283:Rituximab; D000069461:Bendamustine Hydrochloride; D014740:Vidarabine; C024352:fludarabine