Alpha-particle immunotherapy with bismuth-213-labeled anti-CD33 monoclonal antibody HuM195 in myeloid leukemia


Joseph G. Jurcic1, John M. Burke1, Michael R. McDevitt2, Chaitanya R. Divgi3, George Sgouros4, Ronald D. Finn2, Steven M. Larson3, and David A. Scheinberg2. (1) Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 458, New York, NY 10021, (2) Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, (3) Nuclear Medicine Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, (4) Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021
HuM195, a humanized anti-CD33 monoclonal antibody, targets myeloid leukemia cells. The feasibility, safety, and anti-leukemic activity of therapy with the a-emitting radioimmunoconjugate 213Bi-HuM195 was shown in a phase I trial (Jurcic et al. Blood 2002). The physical properties of a particles are ideally suited for treatment of small-volume disease. To determine the effects of a particle immunotherapy against cytoreduced disease, we treated 11 patients with acute myeloid leukemia using the chemotherapeutic agent cytarabine followed by 213Bi-HuM195 0.5-1 mCi/kg (30-90 mCi). Three patients, all treated at the 1 mCi/kg-dose level, responded. Two patients had complete remissions, and one achieved a partial remission. The median time from initiation of therapy to leukocyte recovery was 25 days (range, 17-49 days). One patient had dose-limiting myelosuppression lasting over 35 days. No other significant toxicities were seen. Sequential administration of chemotherapy and 213Bi-HuM195 is safe and can produce remissions in myeloid leukemia.