Alemtuzumab by continuous intravenous infusion followed by subcutaneous injection plus rituximab in the treatment of patients with chronic lymphocytic leukemia recurrence.
BACKGROUND
Monoclonal antibodies may be used more effectively in combination. A previous study of intravenous (iv) bolus alemtuzumab plus rituximab in patients with chronic lymphocytic leukemia (CLL) recurrence produced a response rate of 54% after a 4-week treatment period.


METHODS
To optimize dose, schedule, and route of alemtuzumab, a study was designed exploring continuous intravenous infusion (civ) followed by subcutaneous (sc) alemtuzumab together with weekly iv rituximab in patients with previously treated CLL.


RESULTS
Data from 40 patients with a median age of 59 years, and a median of 3 prior regimens (range, 1-8 regimens) were evaluable. Approximately 64% of patients were fludarabine-refractory. Seven patients (18%) achieved a complete response (CR), 4 (10%) a nodular partial response (nPR), and 10 (25%) a partial response for an overall response rate of 53%. Of 11 major responses (CR, nPR), 8 occurred after cycle 1. Response rates were highest in blood (94%), followed by liver/spleen (82%), bone marrow (68%), and lymph nodes (51%). The combination did not generate unexpected toxicities. Cytomegalovirus (CMV) reactivations occurred in 6 patients (15%) and responded well to anti-CMV therapy. High titers of anti-idiotype antibodies after sc alemtuzumab were demonstrated in 1 patient, but remained without clinical sequelae.


CONCLUSIONS
The combination of civ/sc alemtuzumab plus rituximab has activity in some patients with recurrent/refractory CLL and maximum response is achieved after 1 cycle (4 weeks) in 73% of patients. Further exploration in other settings of CLL together with accompanying pharmacokinetic studies is recommended.
Faderl
Stefan
S
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. sfader@mdanderson.org
Ferrajoli
Alessandra
A
Wierda
William
W
O'Brien
Susan
S
Lerner
Susan
S
Keating
Michael J
MJ
D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000888:Antibodies, Anti-Idiotypic / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007239:Infections / Q000209:etiology; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D000069283:Rituximab; D016896:Treatment Outcome
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm; D000074323:Alemtuzumab; D000069283:Rituximab