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|Title:||Sequential Cytarabine and a-Particle Immunotherapy with Bismuth-213¿Lintuzumab (HuM195) for Acute Myeloid Leukemia|
|Authors:||ROSENBLAT Todd; MCDEVITT Michael; MULFORD D.a.; PANDIT-TASKAR N.; DIVGI C.r.; PANAGEAS Katherine; HEANEY M. L.; CHANEL S.; MORGENSTERN Alfred; SGOUROS George; LARSON S. M.; SCHEINBERG D. A.; JURCIC J. G.|
|Citation:||CLINICAL CANCER RESEARCH vol. 16 no. 21 p. 5303-5311|
|Publisher:||AMER ASSOC CANCER RESEARCH|
|Type:||Articles in Journals|
|Abstract:||Purpose: Lintuzumab (HuM195), a humanized anti-CD33 antibody, targets myeloid leukemia cells and has modest single-agent activity against acute myeloid leukemia (AML). To increase the potency of the antibody without the nonspecific cytotoxicity associated with ß-emitters, the a-particle¿emitting radionuclide bismuth-213 (213Bi) was conjugated to lintuzumab. This phase I/II trial was conducted to determine the maximum tolerated dose (MTD) and antileukemic effects of 213Bi-lintuzumab, the first targeted a-emitter, after partially cytoreductive chemotherapy. Experimental Design: Thirty-one patients with newly diagnosed (n = 13) or relapsed/refractory (n = 18) AML (median age, 67 years; range, 37-80) were treated with cytarabine (200 mg/m2/d) for 5 days followed by 213Bi-lintuzumab (18.5-46.25 MBq/kg). Results: The MTD of 213Bi-lintuzumab was 37 MB/kg; myelosuppression lasting >35 days was dose limiting. Extramedullary toxicities were primarily limited to grade =2 events, including infusion-related reactions. Transient grade 3/4 liver function abnormalities were seen in five patients (16%). Treatment related deaths occurred in 2 of 21 (10%) patients who received the MTD. Significant reductions in marrow blasts were seen at all dose levels. The median response duration was 6 months (range, 2-12). Biodistribution and pharmacokinetic studies suggested that saturation of available CD33 sites by 213Bi-lintuzumab was achieved after partial cytoreduction with cytarabine. Conclusions: Sequential administration of cytarabine and 213Bi-lintuzumab is tolerable and can produce remissions in patients with AML|
|JRC Institute:||Institute for Transuranium Elements|
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