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

J Clin Oncol. 2010 Apr 1;28(10):1749-55. doi: 10.1200/JCO.2009.25.3187. Epub 2010 Mar 1.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00349349.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antigens, CD20 / immunology*
  • Antineoplastic Agents / therapeutic use*
  • Disease-Free Survival
  • Drug Resistance, Neoplasm*
  • Female
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / mortality
  • Male
  • Middle Aged
  • Vidarabine / analogs & derivatives*
  • Vidarabine / therapeutic use

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antigens, CD20
  • Antineoplastic Agents
  • Vidarabine
  • ofatumumab
  • fludarabine

Associated data

  • ClinicalTrials.gov/NCT00349349