Anti-CD123 monoclonal antibodies as therapeutic agents for acute myeloid leukemia: a systematic review

Acute myeloid leukemia is a hematological malignancy characterized by clonal expansion and blockade of myeloid precursor differentiation. This results in poor survival rates, particularly among older patients and those with refractory disease. CD123, the α-chain of the interleukin-3 receptor, is overexpressed in leukemic stem cells and represents a promising therapeutic target.

This systematic review evaluated the efficacy and safety of anti-CD123 monoclonal antibodies administered as standalone treatment or in combination with standard care. The review adhered to the PRISMA statement and Cochrane Handbook.

Eight clinical trials (seven phase I/II trials and one phase III trial) that evaluated antibody-drug conjugates and bispecific antibodies met the inclusion criteria. The interventions demonstrated limited improvements in overall survival and showed frequent treatment-related toxicities such as cytokine release syndrome and dose-limiting adverse events. Most studies included heavily pretreated, relapsed, or refractory patients, which may have contributed to the poor tolerability and limited efficacy.

Future studies should focus on conducting randomized trials with larger sample sizes and greater methodological rigor to validate the clinical utility of anti-CD123 therapies, which currently have a limited impact on overall survival.

This study systematic review was prospectively registered on PROSPERO (identifier CRD4202344450.).