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Keywords:

  • chronic lymphocytic leukemia;
  • monoclonal antibodies;
  • alemtuzumab;
  • rituximab

Abstract

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. Cancer 2010. © 2010 American Cancer Society.