Sequential cytarabine and α-particle immunotherapy with bismuth-213-lintuzumab (HuM195) for acute myeloid leukemia

Todd L. Rosenblat, Michael R. McDevitt, Deborah A. Mulford, Neeta Pandit-Taskar, Chaitanya R. Divgi, Katherine S. Panageas, Mark L. Heaney, Suzanne Chanel, Alfred Morgenstern, George Sgouros, Steven M. Larson, David A. Scheinberg, Joseph G. Jurcic

Research output: Contribution to journalArticlepeer-review

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 β-emitters, the α-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 α-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.

Original languageEnglish (US)
Pages (from-to)5303-5311
Number of pages9
JournalClinical Cancer Research
Volume16
Issue number21
DOIs
StatePublished - Nov 1 2010
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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