• John D Hainsworth, Elizabeth R Vazquez, David R Spigel, Eric Raefsky, James D Bearden, Ruben A Saez, and F Anthony Greco.
• Sarah Cannon Research Institute, Nashville, Tennessee 37203, USA. jhainsworth@tnonc.com
• Cancer. 2008 Mar 15; 112 (6): 1288-95.

BackgroundThe purpose of the current study was to evaluate the efficacy and toxicity of the combination of fludarabine and rituximab, followed by alemtuzumab, as first-line treatment for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).MethodsIn a nonrandomized phase 2 trial, 41 patients who had previously untreated CLL or SLL and required treatment received 4 cycles of the fludarabine and rituximab combination followed 5 weeks later by 4 weeks (12 doses) of intravenous alemtuzumab therapy. The response to treatment was evaluated after completion of treatment with fludarabine and rituximab, and again after the completion of alemtuzumab consolidation.ResultsInitial treatment with the combination of fludarabine and rituximab was well tolerated, and produced a 71% overall response rate (13% complete response). Thirty-four patients began treatment with intravenous alemtuzumab, but this drug was relatively poorly tolerated when given at a short interval after fludarabine and rituximab, and only 20 patients (49% of total) were able to complete the prescribed course. Five patients had an improvement in their response with alemtuzumab; the final complete response rate was 21%. The median progression-free survival for the entire group was 42 months. Toxicity with alemtuzumab included infusion-related toxicity, myelosuppression, and opportunistic infections.ConclusionsThe intravenous schedule of alemtuzumab employed in the trial was relatively poorly tolerated in this community-based trial. The relatively low complete response rates after treatment with the combination of fludarabine and rituximab and after the completion of treatment suggest that these abbreviated courses may compromise efficacy. The generalized use of alemtuzumab as consolidation therapy cannot yet be recommended for community practice. However, optimization of the route of administration, duration of treatment, and interval after completion of induction therapy may improve efficacy, and further investigation is ongoing.Copyright (c) 2008 American Cancer Society.

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