title: Randomized phase 2 study of otlertuzumab and bendamustine versus bendamustine in patients with relapsed chronic lymphocytic leukaemia.
abstract: Otlertuzumab (TRU-016) is a humanized anti-CD37 protein therapeutic that triggers direct caspase-independent apoptosis of malignant B cells and induces antibody-dependent cell-mediated cytotoxicity. Patients with relapsed chronic lymphocytic leukaemia (CLL) received either otlertuzumab (20 mg/kg) weekly by IV infusion for two 28-day cycles then every 14 days for four 28-day cycles and IV bendamustine (70 mg/m2) on Days 1 and 2 of each cycle for up to six 28-day cycles or bendamustine alone. Thirty-two patients were treated with otlertuzumab and bendamustine and 33 with bendamustine alone. Overall response rate according to the International Workshop on Chronic Lymphocytic Leukaemia criteria was 69% in the otlertuzumab and bendamustine arm and 39% in the bendamustine alone arm (P = 0·025). Median progression-free survival (PFS) was 15·9 months in the otlertuzumab and bendamustine arm and 10·2 months in the bendamustine alone arm (P = 0·0192). There was a higher incidence of pyrexia (34% vs. 12%) and neutropenia (59% vs. 39%) with the combination but this did not result in a higher incidence of severe (grade 3/4) infections (13% vs. 27%). This combination significantly increased the response rate and prolonged the PFS over single agent bendamustine in patients with relapsed or refractory CLL.
authors.affiliation: Department of Haematology, Medical University of Lodz and Copernicus Memorial Hospital, Lodz, Poland.
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Robak
authors.affiliation: Department of Hematology, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Hellmann
authors.affiliation: Department of Haematology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Kloczko
authors.affiliation: Haematology, Hospital Universitario La Princesa, IIS-IP Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Loscertales
authors.affiliation: Department of Haematology, Institute of Haematology and Transfusion Medicine, Warsaw, Poland.|Department of Haematology and Transfusion Medicine, Centre of Postgraduate Medical Education, Warsaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Lech-Maranda
authors.affiliation: Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Pagel
authors.affiliation: Center for CLL, University of Pennsylvania and Hackensack University, Philadelphia, PA, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Mato
authors.affiliation: Division of Hematology, The Ohio State University, Columbus, OH, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
authors.affiliation: Division of Hematology, The Ohio State University, Columbus, OH, USA.
authors.forename: Farrukh T
authors.initials: FT
authors.lastname: Awan
authors.affiliation: Department of Haematology/Oncology, Stauferklinikum Schwaebisch Gmuend, Mutlangen, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Hebart
authors.affiliation: Hospital U. Puerta de Hierro-Majadahonda, Madrid, Spain.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Garcia-Marco
authors.affiliation: Department of Hematologic Oncology and Blood Disorders, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Hill
authors.affiliation: Department I of Internal Medicine, Centre of Integrated Oncology Koln and Cluster of Excellence on Cellular Stress Responses in Aging (CECAD) University of Cologne, Cologne, Germany.|German CLL Study Group.
authors.forename: Michael
authors.initials: M
authors.lastname: Hallek
authors.affiliation: Aptevo Therapeutics, Seattle, WA, USA.
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Eisenfeld
authors.affiliation: Aptevo Therapeutics, Seattle, WA, USA.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Stromatt
authors.affiliation: German CLL Study Group.|Department of Medicine I, Division of Haematology and Haemostaseology, Medical University of Vienna, Vienna, Austria.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Jaeger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069461:Bendamustine Hydrochloride / Q000008:administration & dosage* / Q000627:therapeutic use; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000627:therapeutic use; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000627:therapeutic use; D012008:Recurrence; D012074:Remission Induction; D016879:Salvage Therapy / Q000009:adverse effects / Q000379:methods
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; C547387:TRU 016; D000069461:Bendamustine Hydrochloride
keywords: 
  CLL
  ; bendamustine; otlertuzumab