CD123 CAR-T Delivers ~27% CR/CRi in Post-alloHCT AML With Manageable CRS/Neurotoxicity

Single-center, open-label Phase 1 dose-escalation evaluated CD123-directed CAR T cells (autologous or donor-derived allogeneic CAR-T targeting the AML/BPDCN antigen CD123) after lymphodepletion in CD123+ relapsed/refractory AML (Arm 1) or BPDCN (Arm 2) (NCT02159495). Of 41 enrolled, 21 were infused (AML n=19; BPDCN n=2); AML was heavily post-transplant (17/19 [89%] prior alloHCT) and received 50×10^6 (n=2), 200×10^6 (n=6), or 500×10^6 (n=11) CAR-T cells—no DLTs, no prolonged myelosuppression, and no GVHD were reported; CRS was grade ≤3 in 74% and neurotoxicity grade ≤2 in 58%. Among 15 evaluable AML patients, 4/15 (26.7%) achieved CR/CRi, which is in the ballpark of venetoclax-based salvage after post-alloHCT relapse (CR/CRi ~28% in one real-world series), while the BPDCN signal was 1 CR in 2 patients with relapse at 3 months—well below tagraxofusp benchmarks in BPDCN (approved CD123-targeted agent; CR/CRc rates ~54–57% in pivotal datasets).