A pilot dose-escalating study of alemtuzumab plus cyclosporine for patients with bone marrow failure syndrome

The pathogenesis of bone marrow failure syndrome (BMFS) involves both T- and B-cells. Since alemtuzumab (ALM) is a monoclonal anti-CD52 antibody that targets both cell types. we assessed the effects of treatment with ALM and cyclosporine (CS) on 19 patients with BMFS (median age 48 years; range. 16-74 years), including 14 with severe/very severe aplastic anemia (AA), 3 with transfusion-dependent AA and 1 each with myelodysplastic syndrome (MDS) and pure red cell aplasia (PRCA). The (lose of ALM was escalated from dose cohort I (10 mg on day 1, 20 mg on day 2, and 30 mg on day 3) to close cohort II (30 mg/d for 3 days) Plus CS for at least 6 months. Thirteen patients were in dose cohort I and 6 were in dose cohort II. Five patients (23.5%) had a complete response (CR), 2 (11.8%) had it partial response (PR), and 12 (64.7%) had no response, making the overall response rate 36.8% (7/19). The overall response rates in dose cohorts I and II were 46.2% (6/13) and 16.7% (1/6), respectively. Among the 17 patients with AA, the ORR was 35.3% (6/17). 50.0% (6/12) in dose cohort 1 and 0 (0/5) in dose cohort II. Most responsive patients responded within 3 months. Among responders, median time to initial response was 2.07 months (95% CI, 1.40-2.75 months) and median time from initial response to complete response in complete responders was 9.33 months (95% CI. 0.0-31.71 months). The 2-year survival rate was 81.6%. These findings indicate that ALM-CS should be one option for IST in BMFS. and that 60 mg, of ALM may be sufficient compared with the higher dose (90 mg). (C) 2008 Elsevier Ltd. All rights reserved.