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


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.


CONCLUSIONS
Ofatumumab is an active, well-tolerated treatment providing clear clinical improvements for fludarabine-refractory patients with very poor-prognosis CLL.
Wierda
William G
WG
The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-4009, USA. wwierda@mdanderson.org
Kipps
Thomas J
TJ
Mayer
Jirí
J
Stilgenbauer
Stephan
S
Williams
Cathy D
CD
Hellmann
Andrzej
A
Robak
Tadeusz
T
Furman
Richard R
RR
Hillmen
Peter
P
Trneny
Marek
M
Dyer
Martin J S
MJ
Padmanabhan
Swami
S
Piotrowska
Magdalena
M
Kozak
Tomas
T
Chan
Geoffrey
G
Davis
Randy
R
Losic
Nedjad
N
Wilms
Joris
J
Russell
Charlotte A
CA
Osterborg
Anders
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018951:Antigens, CD20 / Q000276:immunology*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D014740:Vidarabine; C527517:ofatumumab; C024352:fludarabine