Ofatumumab As Single-Agent CD20 Immunotherapy in Fludarabine-Refractory CLL

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Journal of Clinical Oncology, 10.1200/JCO.2009.25.3187

Ofatumumab As Single-Agent CD20 Immunotherapy in Fludarabine-Refractory Chronic

Lymphocytic Leukemia

G. Wierda,* J. Kipps, Jií Mayer, Stephan Stilgenbauer, D.

, Andrzej Hellmann, Tadeusz Robak, R. Furman, Hillmen,

Marek Trneny, J.S. Dyer, Swami Padmanabhan, Magdalena Piotrowska, Tomas

Kozak, Geoffrey Chan, Randy , Nedjad Losic, Joris Wilms, Charlotte A.

, and Anders Österborg

From The University of Texas M. D. Cancer Center, Houston, TX;

University of California, San Diego s Cancer Center, La Jolla, CA; Division

of Hematology/Oncology, Weill Cornell Medical College, New York; Roswell Park

Cancer Institute, Buffalo, NY; GlaxoKline, Collegeville, PA; Department of

Internal Medicine/Hemato-Oncology, Faculty Hospital Brno, Brno; First Faculty of

Medicine, University General Hospital; Department of Clinical

Hematology, University Hospital Kralovske Vinohrady, Prague, Czech Republic;

Department of Internal Medicine III, Universitätsklinikum Ulm, Ulm, Germany;

Center for Clinical Haematology, Nottingham University Hospitals, Nottingham; St

' Institute of Oncology, St ' University Hospital, Leeds; Department

of Haematology, Leicester Royal Infirmary, Leicester, United Kingdom; Department

of Hematology, Medical University of Gdansk, Gdansk; Department of Hematology,

Medical University of Lodz, Lodz; Klinika Hematologii Jagiellonian University

Medical College, Krakow, Poland; Genmab, Copenhagen, Denmark; and Department of

Hematology, Karolinska University Hospital, Stockholm, Sweden.

* To whom correspondence should be addressed. E-mail: wwierda@...

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% 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.

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