Vibecotamab for measurable residual disease in acute myeloid leukemia and for myelodysplastic syndromes and chronic myelomonocytic leukemia after hypomethylating agent failure: a phase II study

Acute myeloid leukemia (AML) with persistent measurable residual disease (MRD) and relapsed/refractory myelodysplastic syndromes (MDS) are low-blast myeloid diseases for which there are few effective therapeutic options. CD123 represents an attractive target in these diseases. Vibecotamab is a bispecific antibody that binds to CD123 on malignant blasts and to CD3 on T-cells, to recognize and eliminate CD123-positive malignant cells. This single-center phase II study evaluated the efficacy of vibecotamab in patients AML with detectable MRD (AML-MRD cohort) or with MDS or chronic myelomonocytic leukemia (CMML) after hypomethylating agent failure (MDS/CMML cohort). In cycle 1, patients received vibecotamab IV on day 1 (0.43 µg/kg), day 3 (0.75 µg/kg), day 5 (1.1 µg/kg), and days 8, 15 and 22 (1.7 µg/kg). In subsequent cycles, patients received vibecotamab IV on days 1, 8, 15, and 22 (1.7 µg/kg). The primary outcomes were MRD negativity rate (AML-MRD cohort) and overall response (MDS/CMML cohort). Between May 2022 and April 2025, 48 patients were enrolled (21 AML-MRD cohort, 27 MDS/CMML cohort). The median ages of the AML-MRD and the MDS/CMML cohorts were 70 and 76 years, respectively. In the AML-MRD cohort, the median MRD level by flow cytometry was 0.64% (range, 0.1–3.9%), and in the MDS/CMML, the median bone marrow blast percentage was 7% (range, 3–19%). The AML-MRD clearance rate was 19% (4/21; 95% CI 5–42%), and in the MDS/CMML cohort, the overall response rate was 67% (18/27; 95% CI 46–83%). The median overall survival was 13.1 months (95% CI 8.9-NR) for the AML-MRD cohort and 6.5 months (95% CI 4.2–10.3) for the MDS/CMML cohort. The most frequent adverse event was infusion reaction or cytokine relapse syndrome, which occurred in 29 patients (60%) overall, most of which were grade 1–2. Vibecotamab was active in low-blast myeloid diseases, although the durability of responses was modest. Additional studies of CD123-targeting bispecific antibodies, alone or in combination, are warranted for these diseases. Clinicaltrials.gov (NCT05285813).