7523 Background: Alemtuzumab (Campath-1H) is a fully humanized anti-CD52 antibody used to treat B and T-cell disorders. CD52 is widely expressed on bone marrow lymphoplasmacytic cells and growth supporting mast cells in patients with lymphoplasmacytic lymphoma (LPL), including Waldenstrom’s macroglobulinemia (WM). We therefore examined the activity of alemtuzumab in LPL. Methods: 28 patients with LPL, including 27 WM patients were enrolled in this multicenter study. 23 patients were previously treated. Median age was 60 (range 33–75 years), median prior therapies was 2 (range 0–5), and median time from diagnosis was 2.9 (range 0.1–9.0 years). Baseline median bone marrow involvement was 30% (range 5–90%), median serum IgM was 3510 (range 622–12,000 mg/dL) and hematocrit was 35.1 (range 24.4–42.8%). Patients received 3 test doses of alemtuzumab (3, 10, and 30mg IV) followed by 30 mg TIW for up to 12 weeks. All patients received acyclovir and bactrim or equivalent prophylaxis. Results: Twenty-five patients are evaluable for response. 24/25 patients demonstrated a decrease in serum IgM levels (median change -40.5%), for an overall response rate of 76%, which included 8 (32%) partial responders (≤50% decrease in serum IgM), and 11 (44%) minor responders (≥25% decrease in serum IgM). Hematological toxicities were common among previously treated (but not untreated) patients and included G3/4 neutropenia 39%; thrombocytopenia 18%; anemia 7%. G3/4 non-hematological toxicity for all patients included dermatitis 11%; fatigue 7%; and infection 7%. CMV reactivation and infection was commonly seen among previously treated patients and may have been etiological for one death on study. Two other patients also succumbed on study, one related in part to drug therapy for CMV infection and another due to complications of therapy induced thrombocytopenia and Von Willebrand disease. With a median follow-up of 8.5+ months, 11/19 responding patients remain free of progression. Conclusions: Alemtuzumab is highly active in patients with LPL. Hematological and non-hematological toxicities, including CMV reactivation and infection are common among previously treated patients. Further exploration of this agent in LPL, including upfront therapy is warranted. No significant financial relationships to disclose.