Phase 2 study of vibecotamab for measurable residual disease in AML and for MDS and CMML after failure of hypomethylating agent

Acute myeloid leukemia (AML) with persistent measurable disease (MRD) and relapsed/refractory myelodysplastic syndromes (MDS) are low-blast myeloid diseases for which there are few effective therapeutic options. CD123 is an attractive target in these diseases. Vibecotamab is a bispecific antibody that binds CD123 on malignant blasts and CD3 on T-cells. A phase 2 study at MD Anderson Cancer Center (Houston, TX) evaluated vibecotamab in patients with AML with detectable MRD (AML-MRD cohort; n=21) and patients with MDS or chronic myelomonocytic leukemia (CMML) after hypomethylating agent failure (MDS/CMML cohort; n=27). The median ages of the two cohorts were 70 and 76 years. In the AML-MRD cohort, the median MRD level by flow cytometry was 0.64% (rang 0.1-3.9) and in the MDS/CMML cohort, the median bone marrow blast percentage was 7% (range 3-19). The AML-MRD clearance rate was 19% (95% CI 5-42) and in the MDS/CMML cohort, the overall response rate was 67% (46-83); the median overall survival was 13.1 months (8.9-NR) and 6.5 months (4.2-10.3), respectively. The most frequent adverse event was infusion reaction or cytokine relapse syndrome, which occurred in 29 patients (60%), mostly grade 1-2. The authors conclude that vibecotamab was active in low-blast myeloid diseases, although the durability of responses was modest. Additional studies of CD123-targeting bispecific antibodies are warranted for these diseases.