CD123 expression patterns and selective targeting with a CD123-targeted antibody-drug conjugate (IMGN632) in acute lymphoblastic leukemia

Evgeniya Angelova; Charlene Audette; Yelena Kovtun; Naval Daver; Sa A. Wang; Sherry Pierce; Sergej N. Konoplev; Haitham Khogeer; Jeffrey L. Jorgensen; Marina Konopleva; Patrick A. Zweidler-McKay; L. Jeffrey Medeiros; Hagop M. Kantarjian; Elias J. Jabbour; Joseph D. Khoury

doi:10.3324/haematol.2018.205252

Haematologica (Apr 2019)

CD123 expression patterns and selective targeting with a CD123-targeted antibody-drug conjugate (IMGN632) in acute lymphoblastic leukemia

Evgeniya Angelova,
Charlene Audette,
Yelena Kovtun,
Naval Daver,
Sa A. Wang,
Sherry Pierce,
Sergej N. Konoplev,
Haitham Khogeer,
Jeffrey L. Jorgensen,
Marina Konopleva,
Patrick A. Zweidler-McKay,
L. Jeffrey Medeiros,
Hagop M. Kantarjian,
Elias J. Jabbour,
Joseph D. Khoury

Affiliations

Evgeniya Angelova: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX
Charlene Audette: ImmunoGen, Inc., Waltham, MA
Yelena Kovtun: ImmunoGen, Inc., Waltham, MA
Naval Daver: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Sa A. Wang: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX
Sherry Pierce: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Sergej N. Konoplev: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX
Haitham Khogeer: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX
Jeffrey L. Jorgensen: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX
Marina Konopleva: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Patrick A. Zweidler-McKay: ImmunoGen, Inc., Waltham, MA
L. Jeffrey Medeiros: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX
Hagop M. Kantarjian: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Elias J. Jabbour: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Joseph D. Khoury: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX

DOI: https://doi.org/10.3324/haematol.2018.205252
Journal volume & issue: Vol. 104, no. 4

Abstract

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The potential of CD123-targeted therapies in acute lymphoblastic leukemia/lymphoma remains largely unexplored. We examined CD123 expression levels in a large cohort of patients with acute lymphoblastic leukemia/lymphoma and assessed the in vitro impact of IMGN632, a conjugate of CD123-binding antibody with a novel DNA-alkylating payload. CD123 expression on leukemic blasts was surveyed using multicolor/multiparameter flow cytometry. The in vitro effect of IMGN632 was evaluated on B acute lymphoblastic leukemia/lymphoma cell lines and primary B acute lymphoblastic leukemia/lymphoma blasts. The study cohort (n=213) included 183 patients with B acute lymphoblastic leukemia/lymphoma and 30 with T acute lymphoblastic leukemia/lymphoma. CD123 expression was more prevalent in B acute lymphoblastic leukemia/lymphoma than in T acute lymphoblastic leukemia/lymphoma (164/183, 89.6% versus 13/30, 43.3%; P

Published in Haematologica

ISSN: 0390-6078 (Print); 1592-8721 (Online)
Publisher: Ferrata Storti Foundation
Country of publisher: Italy
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the blood and blood-forming organs
Website: http://www.haematologica.org

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