Phase 1 data reported for anti-CD123 CAR T-cell therapy in relapsed or refractory AML, BPDCN 

CD123–directed chimeric antigen receptor T-cell therapy was feasible with a favorable safety profile for patients with relapsed or refractory acute myeloid leukemia or blastic plasmacytoid dendritic cell neoplasm, including those with prior allogeneic hematopoietic stem cell transplant, according to a single-center, phase 1 dose escalation trial. 

The study’s authors, led by Lihua E Budde, MD, PhD, of City of Hope in Duarte, California, published the findings in the Journal of Hematology & Oncology. 

In the study, 21 out of 41 enrolled patients received CD123 CAR T-cell infusions, including 19 with AML and two with BPDCN. The median age of patients with AML was 45 years (range, 20-71), and the patients with BPDCN were aged 24 and 75 years. The majority of patients with AML had received prior allogeneic HSCT (89%). Trial doses included 50×10⁶, 200×10⁶, and 500×10⁶ for two, six, and 11 patients with AML, and 100×106 for both patients with BPDCN. 

There were no dose-limiting toxicities, prolonged myelosuppression, or graft-versus-host disease in any patients. CAR T-cell expansion was dose–dependent, but persistence was limited. Among patients with AML, 14 developed grade 3 or lower cytokine release syndrome and 11 developed grade 2 or lower neurotoxicity. Neither patient with BPDCN developed CRS, although both developed grade 1 neurotoxicity.

Out of 19 patients with AML that received CD123 CAR T-cell infusion, 15 were evaluable for response. Of these, four (26.7%) achieved complete remission, including two with incomplete count recovery. One of the two BPDCND patients achieved complete remission but relapsed at three months.

“Although the estimated overall complete remission rate was modest, these findings provide a foundation for further optimization of CD123 CAR T-cell design, patient selection, and combination strategies,” the authors wrote. 

Reference

Budde LE, Del Real MM, Song J, et al. A phase 1 trial of CD123-directed chimeric antigen receptor T-cell therapy in adults with relapsed/refractory acute myeloid leukemia or blastic plasmacytoid dendritic cell neoplasm. J Hematol Oncol (2026). https://doi.org/10.1186/s13045-026-01833-3