Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2010 Nov 1;16(21):5303-11.
doi: 10.1158/1078-0432.CCR-10-0382. Epub 2010 Sep 21.

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

Todd L Rosenblat  1 , 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
Affiliations
Clinical Trial

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

Todd L Rosenblat et al. Clin Cancer Res. .

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 ((213)Bi) was conjugated to lintuzumab. This phase I/II trial was conducted to determine the maximum tolerated dose (MTD) and antileukemic effects of (213)Bi-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/m(2)/d) for 5 days followed by (213)Bi-lintuzumab (18.5-46.25 MBq/kg).

Results: The MTD of (213)Bi-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 (213)Bi-lintuzumab was achieved after partial cytoreduction with cytarabine.

Conclusions: Sequential administration of cytarabine and (213)Bi-lintuzumab is tolerable and can produce remissions in patients with AML.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Percentage change in bone marrow blasts after treatment with sequential cytarabine and 213Bi-lintuzumab in 26 evaluable patients.
Fig. 2
Fig. 2
Kaplan-Meier plot showing the probability of survival for patients with previously untreated AML and those with relapsed or refractory disease.
Fig. 3
Fig. 3
Gamma camera images show targeting of isotope to marrow, liver, and spleen after the first injection (A) and blood pooling after the last (B). Rate images show uptake of 213Bi by target organs over 1 hour after the first injection (C) and clearance after the last (D). Time-activity curves demonstrate localization and retention of 213Bi in the marrow (E) and liver (F). (-○-), 1st injection; (-◆-), 4th injection.
See this image and copyright information in PMC

References

    1. Cassileth PA, Harrington DP, Appelbaum FR, et al. Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission. N Engl J Med. 1998;339:1649–56. - PubMed
    1. Stockerl-Goldstein KE, Blume KG. Allogeneic hematopoietic cell transplantation for adult patients with acute myeloid leukemia. In: Thomas ED, Blume KG, Forman SJ, editors. Hematopoietic Cell Transplantation. Oxford: Blackwell Science, Inc; 1999. pp. 823–34.
    1. Horner MJ, Ries LAG, Krapcho M, et al., editors. SEER cancer statistics review, 1975–2006. National Cancer Institute; Bethesda, MD: http://seer.cancer.gov/csr/1975_2006/, based on November 2008 SEER data submission, posted to the SEER web site, 2009.
    1. Burke JM, Caron PC, Papadopoulos EB, et al. Cytoreduction with iodine-131-anti-CD33 antibodies before bone marrow transplantation for advanced myeloid leukemias. Bone Marrow Transplant. 2003;32:549–56. - PubMed
    1. Jurcic JG, Divgi CR, McDevitt MR, et al. Potential for myeloablation with yttrium-90-HuM195 (anti-CD33) in myeloid leukemia. Proc Am Soc Clin Oncol. 2000;19:8a.

Publication types

MeSH terms