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

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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