Sequential cytarabine and α-particle immunotherapy with bismuth-213-lintuzumab (HuM195) for acute myeloid leukemia Journal Article
| Authors: | Rosenblat, T. L.; McDevitt, M. R.; Mulford, D. A.; Pandit-Taskar, N.; Divgi, C. R.; Panageas, K. S.; Heaney, M. L.; Chanel, S.; Morgenstern, A.; Sgouros, G.; Larson, S. M.; Scheinberg, D. A.; Jurcic, J. G. |
| Article Title: | Sequential cytarabine and α-particle immunotherapy with bismuth-213-lintuzumab (HuM195) for acute myeloid leukemia |
| 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. ©2010 AACR. |
| Keywords: | adult; clinical article; controlled study; treatment outcome; aged; aged, 80 and over; middle aged; unclassified drug; acute granulocytic leukemia; leukemia, myeloid, acute; clinical trial; drug tolerability; neutropenia; gastrointestinal hemorrhage; side effect; cytarabine; antineoplastic agent; cancer immunotherapy; controlled clinical trial; liver toxicity; phase 2 clinical trial; antimetabolites, antineoplastic; thrombocytopenia; drug administration schedule; antineoplastic activity; continuous infusion; chill; drug fever; febrile neutropenia; pneumonia; cancer regression; antibodies, monoclonal; rigor; drug distribution; remission induction; maximum tolerated dose; phase 1 clinical trial; radioimmunotherapy; drug dose regimen; radioisotopes; bacterial infection; drug dose sequence; alpha radiation; immunoconjugates; bismuth; hum 195; lintuzumab bi 213; candidemia; alpha particles |
| Journal Title: | Clinical Cancer Research |
| Volume: | 16 |
| Issue: | 21 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2010-11-01 |
| Start Page: | 5303 |
| End Page: | 5311 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-10-0382 |
| PUBMED: | 20858843 |
| PROVIDER: | scopus |
| PMCID: | PMC2970691 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 20 April 2011" - "CODEN: CCREF" - "Source: Scopus" |
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