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.
Article highlights
Because of well-defined cell surface antigens, easy accessibility, and radiosensitivity of leukemia cells, there is long-standing interest in radioimmunotherapy (RIT) for acute myeloid leukemia (AML).
Targeting primarily CD33, CD45, or CD66, early RIT efforts have focused on β-emitters, including 131I and 90Y, mostly to intensify conditioning therapy before allogeneic hematopoietic cell transplantation (HCT).
Building on early single-institution data, an 131I-labeled CD45 antibody (Iomab-B [apamistamab-I131]) is currently studied as a component of an HCT-conditioning regimen in the registration-type, multicenter phase 3 SIERRA trial (NCT02665065).
While efforts with β-emitters continue, there is growing interest in α-particle emitting radionuclides such as 225Ac or 211At as therapeutic payloads.
α-emitters 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.
The prospect of a first anti-AML RIT becoming available soon may propel further work to develop RIT-based treatments for AML, with many such efforts already ongoing.
Declaration of interest
RB Walter received laboratory research grants and/or clinical trial support from Agios, Amgen, Aptevo, Arog, BioLineRx, Celgene, ImmunoGen, Janssen, Jazz, Kura, MacroGenics, Pfizer, Selvita, and Stemline; has ownership interests in Amphivena; and is (or has been) a consultant to Agios, Amgen, Amphivena, Aptevo, Astellas, BioLineRx, Boston Biomedical, Bristol Myers Squibb, Celgene, Genentech, GlaxoSmithKline, Janssen, Jazz, Kite, Kronos, MacroGenics, New Link Genetics, Pfizer, and Race. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Reviewer disclosures
Peer reviewers of this manuscript have no relevant financial or other relationships to disclose.