Radioimmunotherapy as a targeted strategy of reduced-intensity conditioning for allogeneic transplantation in leukemia.

Reduced-intensity conditioning (RIC) has expanded the use of allogeneic hematopoietic transplant (allo-HCT) as a potentially curative treatment of a variety of hematological cancers including acute myeloid leukemia (AML) by reducing treatment-related morbidity and mortality. However, the RIC allo HCT success is limited by relapse, especially for patients with adverse molecular/cytogenetics or with measurable residual disease (MRD) at the time of HCT. Radioimmunotherapy (RIT) potentially improves the efficacy of RIC by enhancing the cytoreductive effect with the ability to deliver targeted radiation to sites of hematopoietic malignancy while sparing nonhematopoietic organs. In clinical trials using different combinations of targeting antibodies and radionuclides, reliable radiation targeting to marrow and spleen has been consistently demonstrated. Toxicity is often predictable and organ-specific with hepatic toxicity most commonly limiting the therapeutic dose. In this article, we review the rationale for combining RIT with RIC and discuss antigen selection and distinct properties of β- and α-emitting radionuclides. We also summarize clinical experience combining fludarabine-based RIC regimens with RIT and provide emerging directions, including the development of α-emitter platforms. Available data suggest that RIT may potentially improve disease control while maintaining the tolerability of RIC. Because the majority of the current evidence involves early-phase studies, additional prospective evaluation is needed before radioimmunotherapy can be considered a standard component of conditioning.