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

被引:464
作者
Wierda, William G. [1 ]
Kipps, Thomas J.
Mayer, Jiri
Stilgenbauer, Stephan
Williams, Cathy D.
Hellmann, Andrzej
Robak, Tadeusz
Furman, Richard R.
Hillmen, Peter
Trneny, Marek
Dyer, Martin J. S.
Padmanabhan, Swami
Piotrowska, Magdalena
Kozak, Tomas
Chan, Geoffrey
Davis, Randy
Losic, Nedjad
Wilms, Joris
Russell, Charlotte A.
Oesterborg, Anders
机构
[1] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA
基金
英国医学研究理事会;
关键词
PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; PLUS CYCLOPHOSPHAMIDE; MONOCLONAL-ANTIBODIES; FOLLICULAR LYMPHOMA; ANTI-CD20; ANTIBODY; RITUXIMAB THERAPY; ALEMTUZUMAB; PATIENT; TRIAL; CHEMOIMMUNOTHERAPY;
D O I
10.1200/JCO.2009.25.3187
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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. J Clin Oncol 28: 1749-1755. (C) 2010 by American Society of Clinical Oncology
引用
收藏
页码:1749 / 1755
页数:7
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