Tagraxofusp (CD123-directed cytotoxin) in BPDCN delivers 71%–90% ORR across trials—HSCT bridge drives survival

Tagraxofusp (tagraxofusp-erzs; ELZONRIS) is an IL-3Rα/CD123-targeted recombinant fusion “cytotoxin” (IL-3 linked to truncated diphtheria toxin) evaluated in a systematic review of adult BPDCN outcomes across prospective trials and real-world series through January 25, 2026. Across 27 studies totaling 343 unique adults, frontline clinical trials reported ORR 71%–90% with CR/CRc 56%–72%, while real-world cohorts showed ORR 65%–90% and consistently better long-term outcomes in patients successfully bridged to allogeneic HSCT; this is broadly directionally consistent with the pivotal Phase I/II program (NCT02113982), which reported high response rates in untreated BPDCN in a non-randomized setting. The defining safety issue remained capillary leak syndrome (CLS) with variable incidence across settings; in longer-term follow-up of NCT02113982, CLS occurred in ~21% overall with grade ≥3 ~7%, underscoring that “response depth” is only part of the story if patients can’t safely stay on drug long enough to reach transplant.