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 dose 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 dose 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 a 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).