title: Bendamustine and rituximab in combination with lenalidomide in patients with chronic lymphocytic leukemia.
abstract: OBJECTIVE
  A phase I/II trial to assess safety and efficacy of the combination bendamustine, rituximab, and lenalidomide (BRL) in patients with chronic lymphocytic leukemia (CLL).
  
  
  METHODS
  Seventeen relapsed or refractory (R/R) and five previously untreated (FL) CLL patients were enrolled in the trial. In the R/R cohort, four different dose levels of lenalidomide (maximum 15 mg/d) were used. In the FL cohort, lenalidomide was dose escalated from 5 mg/d to 15 mg/d. Bendamustine was used at doses of 50 or 90 mg/m(2) for R/R or FL treatment, respectively. 375 mg/m(2) Rituximab were used for the first and 500 mg/m(2) for subsequent treatment courses. Treatment consisted of up to six courses of 28 d.
  
  
  RESULTS
  The maximal tolerable dose of lenalidomide was 5 mg/d. The response rate was 47.1% in R/R and 60% in FL patients. Median progression-free survival was 8.0 months. Median overall survival was 22.9 and 12.3 months, respectively, in R/R and FL patients. Grade 3/4 hematological toxicity was observed in 71.4%, and severe infections in 47.6% of patients. Due to high toxicity and low response rate of BRL, the trial was closed prematurely.
  
  
  CONCLUSIONS
  BRL was associated with a high toxicity rate, a high number of treatment interruptions, and a low remission rate. Therefore, BRL cannot be considered an appropriate treatment option for patients with CLL.
authors.affiliation: Department I of Internal Medicine, Center of Integrated Oncology Cologne Bonn, University of Cologne, Cologne, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Maurer
authors.affiliation: Department I of Internal Medicine, Center of Integrated Oncology Cologne Bonn, University of Cologne, Cologne, Germany.
authors.forename: Natali
authors.initials: N
authors.lastname: Pflug
authors.affiliation: Department I of Internal Medicine, Center of Integrated Oncology Cologne Bonn, University of Cologne, Cologne, Germany.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Bahlo
authors.affiliation: Department I of Internal Medicine, Center of Integrated Oncology Cologne Bonn, University of Cologne, Cologne, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Kluth
authors.affiliation: Department I of Internal Medicine, Center of Integrated Oncology Cologne Bonn, University of Cologne, Cologne, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Rhein
authors.affiliation: Department I of Internal Medicine, Center of Integrated Oncology Cologne Bonn, University of Cologne, Cologne, Germany.
authors.forename: Paula
authors.initials: P
authors.lastname: Cramer
authors.affiliation: Department I of Internal Medicine, Center of Integrated Oncology Cologne Bonn, University of Cologne, Cologne, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Gross-Ophoff
authors.affiliation: Department I of Internal Medicine, Center of Integrated Oncology Cologne Bonn, University of Cologne, Cologne, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Langerbeins
authors.affiliation: Department I of Internal Medicine, Center of Integrated Oncology Cologne Bonn, University of Cologne, Cologne, Germany.
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Fink
authors.affiliation: Department I of Internal Medicine, Center of Integrated Oncology Cologne Bonn, University of Cologne, Cologne, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Eichhorst
authors.affiliation: Department I of Internal Medicine, Center of Integrated Oncology Cologne Bonn, University of Cologne, Cologne, Germany.
authors.forename: Karl-Anton
authors.initials: KA
authors.lastname: Kreuzer
authors.affiliation: Department of Hematology, Oncology, Immunology, Palliative Care, Infectious Diseases and Tropical Medicine, Klinikum Schwabing, Munich, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Fischer
authors.affiliation: Department of Internal Medicine III, University of Ulm, Ulm, Germany.
authors.forename: Eugen
authors.initials: E
authors.lastname: Tausch
authors.affiliation: Department of Internal Medicine III, University of Ulm, Ulm, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Stilgenbauer
authors.affiliation: Second Department of Medicine, University Hospital of Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Böttcher
authors.affiliation: Department of Internal Medicine III, University of Ulm, Ulm, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Döhner
authors.affiliation: Second Department of Medicine, University Hospital of Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Kneba
authors.affiliation: Department of Medicine III, Hospital of the University LMU München, München, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Dreyling
authors.affiliation: Department of Oncology and Hematology, BMT with Section Pneumology, Hubertus Wald Tumorzentrum/UVVH, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Mascha
authors.initials: M
authors.lastname: Binder
authors.affiliation: Department I of Internal Medicine, Center of Integrated Oncology Köln Bonn, Cluster of Excellence on "Cellular Stress Responses in Aging" (CECAD), University of Cologne, Cologne, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hallek
authors.affiliation: Department I of Internal Medicine, Center of Integrated Oncology Cologne Bonn, University of Cologne, Cologne, Germany.|Department of Hematology, Oncology, Immunology, Palliative Care, Infectious Diseases and Tropical Medicine, Klinikum Schwabing, Munich, Germany.
authors.forename: Clemens-Martin
authors.initials: CM
authors.lastname: Wendtner
authors.affiliation: Department of Hematology, Oncology, Immunology, Palliative Care, Infectious Diseases and Tropical Medicine, Klinikum Schwabing, Munich, Germany.
authors.forename: Manuela
authors.initials: M
authors.lastname: Bergmann
authors.affiliation: Department I of Internal Medicine, Center of Integrated Oncology Cologne Bonn, University of Cologne, Cologne, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Fischer
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069461:Bendamustine Hydrochloride / Q000008:administration & dosage; D002869:Chromosome Aberrations; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D000069283:Rituximab / Q000008:administration & dosage; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome
chemical_list: D000069283:Rituximab; D013792:Thalidomide; D000069461:Bendamustine Hydrochloride; D000077269:Lenalidomide
keywords: combination treatment with lenalidomide; dose levels; dose limiting toxicity; overall response rate; toxicity