Published on October 22, 2026
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
by Alex Kadhim
Researchers at the the Department of Hematology and Hematopoietic Cell Transplantation, with correlative analyses contributed by the University of Washington and the Keck School of Medicine of USC, have exhibited that CD123 is able to be targeted using chimeric antigen receptor (CAR) T cells without the myeloablation that preclinical work with other constructs predicted, though remissions proved uncommon and brief. As reported in the Journal of Hematology & Oncology, the investigators recorded no dose-limiting toxicity, no prolonged myelosuppression, and no graft-versus-host disease at any dose level.
CD123, the interleukin-3 receptor alpha subunit, is expressed in roughly 70% of acute myeloid leukemia (AML) as well as on leukemic stem cells, and is pathognomonic for blastic plasmacytoid dendritic cell neoplasm (BPDCN). Its higher density on blasts than on normal hematopoietic stem cells makes it attractive, but on-target hematologic toxicity has been of notable concern. This single-center, open-label, two-arm dose-escalation study (NCT02159495) infused a second-generation, CD28-costimulated CAR bearing truncated epidermal growth factor receptor for detection, manufactured from patient cells or from the donor of a prior allogeneic hematopoietic cell transplantation (alloHCT), following fludarabine and cyclophosphamide lymphodepletion. Toxicity and disease response were co-primary endpoints.
Products were manufactured for 37 of 41 enrolled patients (90%), and 21 were infused: 19 with AML (median age 45 years, range 20 to 71; 89% with prior alloHCT) and 2 with BPDCN. AML doses were 50 × 10⁶ (n = 2), 200 × 10⁶ (n = 6), or 500 × 10⁶ (n = 11) cells. Cytokine release syndrome affected 14 patients (74%), with none above grade 3, and 11 (58%) possessing grade 2 or lower neurotoxicity, all resolving. Of 15 evaluable AML patients, 4 (26.7%) reached complete remission or complete remission with incomplete count recovery, with a median overall survival of 11.3 months (95% CI, 6.9 to 14.5). Expansion tracked with dose (mean maximum vector log₁₀ 1.8, 3.5, 4.7), however, but with distinction between responders and non-responders (difference 1.1; 95% CI, −1.43 to 3.55). CD123 was lost or downregulated in 5 of 7 evaluable patients by day 28, with recommended phase 2 dose reached.
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;19:68. https:doi.org/10.1186/s13045-026-01833-3
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