Where do we stand with radioimmunotherapy for acute myeloid leukemia?

Abstract

ABSTRACT Introduction Despite the approval of several new drugs, deaths from acute myeloid leukemia (AML) remain common. Because of well-defined cell surface antigens, easy accessibility, and radiosensitivity of leukemia cells, there is long-standing interest in radiolabeled antibodies (radioimmunotherapy [RIT]) to complement or replace existing treatments and improve outcomes in AML. Areas covered Targeting primarily CD33, CD45, or CD66, early RIT efforts have focused on β-emitters, including iodine-131 (131I) and yttrium-90, mostly to intensify conditioning therapy before allogeneic hematopoietic cell transplantation (HCT). An 131I-labeled CD45 antibody (Iomab-B [apamistamab-I131]) is currently studied in the registration-type phase 3 SIERRA trial (NCT02665065) for this purpose. Of growing interest as therapeutic payloads are α-particle emitting radionuclides such as actinium-225 (225Ac) or astatine-211 (211At) since they deliver substantially higher decay energies over a much shorter distance than β-emitters, rendering them more suitable for precise, potent, and efficient target cell killing while minimizing toxicity to surrounding bystander cells, possibly allowing use outside of HCT. Clinical efforts with 211At-labeled CD45 antibodies and 225Ac-labeled CD33 antibodies (e.g. 225Ac-lintuzumab [Actimab-A]) are ongoing. Expert opinion A first anti-AML RIT may soon become available. This might propel further work to develop RIT-based treatments for AML, with many such efforts already ongoing.