Treatment of patients with acute myeloid leukemia with the targeted alpha-particle nanogenerator (225)actinium-lintuzumab Journal Article

Authors: Rosenblat, T. L.; McDevitt, M. R.; Carrasquillo, J. A.; Pandit-Taskar, N.; Frattini, M. G.; Maslak, P. G.; Park, J. H.; Douer, D.; Cicic, D.; Larson, S. M.; Scheinberg, D. A.; Jurcic, J. G.
Article Title: Treatment of patients with acute myeloid leukemia with the targeted alpha-particle nanogenerator (225)actinium-lintuzumab
Abstract: PURPOSE: The anti-CD33 antibody lintuzumab has modest activity against acute myeloid leukemia (AML). To increase its potency, lintuzumab was conjugated to actinium-225 (225Ac), a radionuclide yielding 4 α-particles. This first-in-human, phase I trial was conducted to determine the safety, pharmacology, and biological activity of 225Ac-lintuzumab. PATIENTS AND METHODS: Eighteen patients (median age, 64 years; range, 45-80) with relapsed or refractory AML received a single infusion of 225Ac-lintuzumab at activities of 18.5 to 148 kBq/kg. RESULTS: The maximum tolerated dose was 111 kBq/kg. Dose-limiting toxicities included myelosuppression lasting > 35 days in one patient receiving 148 kBq/kg and death from sepsis in two patients treated with 111 and 148 kBq/kg. Myelosuppression was the most common toxicity. Significant extramedullary toxicities were limited to transient grade 3 liver function abnormalities. Pharmacokinetics were determined by gamma counting serial whole blood, plasma, and urine samples at energy windows for the 225Ac daughters, francium-221 and bismuth-213. Two-phase elimination kinetics were seen with mean plasma t1/2 - α and t1/2 - β of 1.9 and 38 hours, respectively. Peripheral blood blasts were eliminated in 10 of 16 evaluable patients (63%) but only at doses of ≥ 37 kBq/kg. Bone marrow blasts were reduced in 10 of 15 evaluable patients (67%), including 3 patients with marrow blasts ≤ 5% and one patient with a morphologic leukemia-free state. CONCLUSIONS: Therapy for AML with the targeted α-particle generator 225Ac-lintuzumab was feasible with an acceptable safety profile. Elimination of circulating blasts or reductions in marrow blasts were observed across all dose levels. ©2022 American Association for Cancer Research.
Keywords: middle aged; leukemia, myeloid, acute; monoclonal antibody; adverse event; alpha radiation; antibody conjugate; immunoconjugates; alpha particles; actinium; acute myeloid leukemia; actinium-225; lintuzumab; antibodies, monoclonal, humanized; humans; human
Journal Title: Clinical Cancer Research
Volume: 28
Issue: 10
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2022-05-15
Start Page: 2030
End Page: 2037
Language: English
DOI: 10.1158/1078-0432.Ccr-21-3712
PUBMED: 35247915
PROVIDER: scopus
PMCID: PMC9106874
Notes: Article -- Export Date: 1 June 2022 -- Source: Scopus
Citation Impact
MSK Authors
  1. Michael R Mcdevitt
    135 Mcdevitt
  2. Jae Hong Park
    237 Park
  3. Peter Maslak
    195 Maslak
  4. Steven M Larson
    916 Larson