Ofatumumab as single-agent CD20 immunotherapy in fludarabine-refractory chronic lymphocytic leukemia

William G Wierda, Thomas J Kipps, Jirí Mayer, Stephan Stilgenbauer, Cathy D Williams, Andrzej Hellmann, Tadeusz Robak, Richard R Furman, Peter Hillmen, Marek Trneny, Martin J S Dyer, Swaminathan Padmanabhan Iyer, Magdalena Piotrowska, Tomas Kozak, Geoffrey Chan, Randy Davis, Nedjad Losic, Joris Wilms, Charlotte A Russell, Anders OsterborgHx-CD20-406 Study Investigators

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524 Scopus citations


PURPOSE: 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.

PATIENTS AND 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.

CONCLUSION: Ofatumumab is an active, well-tolerated treatment providing clear clinical improvements for fludarabine-refractory patients with very poor-prognosis CLL.

Original languageEnglish (US)
Pages (from-to)1749-55
Number of pages7
JournalJournal of Clinical Oncology
Issue number10
StatePublished - Apr 1 2010


  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal
  • Antigens, CD20
  • Antineoplastic Agents
  • Disease-Free Survival
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Male
  • Middle Aged
  • Vidarabine
  • Clinical Trial
  • Journal Article
  • Multicenter Study


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