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

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.

• Authors: 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, Swami Padmanabhan, Magdalena Piotrowska, Tomas Kozak, Geoffrey Chan, Randy Davis, Nedjad Losic, Joris Wilms, Charlotte A Russell, Anders Osterborg, Hx-CD20-406 Study Investigators
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 28 Issue 10 Pg. 1749-55 (Apr 01 2010) ISSN: 1527-7755 [Electronic] United States
• PMID: 20194866 (Publication Type: Clinical Trial, Journal Article, Multicenter Study)

Chemical References

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

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal (adverse effects, 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, mortality)
• Male
• Middle Aged
• Vidarabine (analogs & derivatives, therapeutic use)