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

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