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Alemtuzumab by continuous intravenous infusion followed by subcutaneous injection plus rituximab in the treatment of patients with chronic lymphocytic leukemia recurrence
Article first published online: 11 MAR 2010
Copyright © 2010 American Cancer Society
Volume 116, Issue 10, pages 2360–2365, 15 May 2010
How to Cite
Faderl, S., Ferrajoli, A., Wierda, W., O'Brien, S., Lerner, S. and Keating, M. J. (2010), Alemtuzumab by continuous intravenous infusion followed by subcutaneous injection plus rituximab in the treatment of patients with chronic lymphocytic leukemia recurrence. Cancer, 116: 2360–2365. doi: 10.1002/cncr.24958
- Issue published online: 28 APR 2010
- Article first published online: 11 MAR 2010
- Manuscript Accepted: 10 AUG 2009
- Manuscript Revised: 7 JUL 2009
- Manuscript Received: 5 APR 2009
Vol. 116, Issue 16, 3982, Article first published online: 1 JUN 2010
- chronic lymphocytic leukemia;
- monoclonal antibodies;
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.
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.
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.
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. Cancer 2010. © 2010 American Cancer Society.