title: Ofatumumab as single-agent CD20 immunotherapy in fludarabine-refractory chronic lymphocytic leukemia.
abstract: OBJECTIVE
  New treatments are needed for patients with fludarabine- and alemtuzumab-refractory (FA-ref) chronic lymphocytic leukemia (CLL) or patients with fludarabine-refractory CLL with bulky (> 5 cm) lymphadenopathy (BF-ref) who are less suitable for alemtuzumab treatment; these groups have poor outcomes with available salvage regimens. Ofatumumab (HuMax-CD20) is a human monoclonal antibody targeting a distinct small-loop epitope on the CD20 molecule. We conducted an international clinical study to evaluate the efficacy and safety of ofatumumab in patients with FA-ref and BF-ref CLL.
  
  
  METHODS
  Patients received eight weekly infusions of ofatumumab followed by four monthly infusions during a 24-week period (dose 1 = 300 mg; doses 2 to 12 = 2,000 mg); response by an independent review committee (1996 National Cancer Institute Working Group criteria) was assessed every 4 weeks until week 24 and then every 3 months until month 24.
  
  
  RESULTS
  This planned interim analysis included 138 treated patients with FA-ref (n = 59) and BF-ref (n = 79) CLL. The overall response rates (primary end point) were 58% [corrected] and 47% in the FA-ref and BF-ref groups, respectively. Complete resolution of constitutional symptoms and improved performance status occurred in 57% and 48% of patients, respectively. Median progression-free survival and overall survival times were 5.7 and 13.7 months in the FA-ref group, respectively, and 5.9 and 15.4 months in the BF-ref group, respectively. The most common adverse events during treatment were infusion reactions and infections, which were primarily grade 1 or 2 events. Hematologic events during treatment included anemia and neutropenia.
  
  
  CONCLUSIONS
  Ofatumumab is an active, well-tolerated treatment providing clear clinical improvements for fludarabine-refractory patients with very poor-prognosis CLL.
authors.affiliation: The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-4009, USA. wwierda@mdanderson.org
authors.forename: William G
authors.initials: WG
authors.lastname: Wierda
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Kipps
authors.forename: Jirí
authors.initials: J
authors.lastname: Mayer
authors.forename: Stephan
authors.initials: S
authors.lastname: Stilgenbauer
authors.forename: Cathy D
authors.initials: CD
authors.lastname: Williams
authors.forename: Andrzej
authors.initials: A
authors.lastname: Hellmann
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Robak
authors.forename: Richard R
authors.initials: RR
authors.lastname: Furman
authors.forename: Peter
authors.initials: P
authors.lastname: Hillmen
authors.forename: Marek
authors.initials: M
authors.lastname: Trneny
authors.forename: Martin J S
authors.initials: MJ
authors.lastname: Dyer
authors.forename: Swami
authors.initials: S
authors.lastname: Padmanabhan
authors.forename: Magdalena
authors.initials: M
authors.lastname: Piotrowska
authors.forename: Tomas
authors.initials: T
authors.lastname: Kozak
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Chan
authors.forename: Randy
authors.initials: R
authors.lastname: Davis
authors.forename: Nedjad
authors.initials: N
authors.lastname: Losic
authors.forename: Joris
authors.initials: J
authors.lastname: Wilms
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Russell
authors.forename: Anders
authors.initials: A
authors.lastname: Osterborg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018951:Antigens, CD20 / Q000276:immunology*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D014740:Vidarabine; C527517:ofatumumab; C024352:fludarabine