Where do we stand with radioimmunotherapy for acute myeloid leukemia?

摘要

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 beta-emitters, including iodine-131 (I-131) and yttrium-90, mostly to intensify conditioning therapy before allogeneic hematopoietic cell transplantation (HCT). An I-131-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 alpha-particle emitting radionuclides such as actinium-225 (Ac-225) or astatine-211 (At-211) since they deliver substantially higher decay energies over a much shorter distance than beta-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 At-211-labeled CD45 antibodies and Ac-225-labeled CD33 antibodies (e.g. Ac-225-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.