Abstract / Summary
Abstract Tagraxofusp (TAG), a CD123-directed protein-drug conjugate, is approved in front-line and relapsed/refractory blastic plasmacytoid dendritic cell neoplasm (BPDCN). Multicenter real-world outcomes and the contribution of up-front consolidation post-TAG remain less defined. We retrospectively analyzed 32 patients with BPDCN treated with frontline TAG (2019–2024) across 13 tertiary centers, contextualized against a historical cohort treated before TAG availability ( n = 40). Patients were elderly (median age 71.5 years) with advanced disease, including skin (93.8%), bone marrow (84.4%), and peripheral blood involvement (53.1%). The overall response rate to TAG was 82.1%, with complete responses in 60.7%. Capillary leak syndrome occurred in 53.1% (grade ≥ 3 in 47.1%), with no unexpected safety signals. With a median follow-up of 18.4 months, 2-year overall survival (OS) and progression-free survival were 40.5% and 30.4%. Nearly half of patients proceeded to allogeneic stem cell transplantation post-TAG, associated with improved survival consistent with the primary analysis and landmark-adjusted analyses (HR 0.25 [0.06–1.14]; p = 0.073). Propensity score–matched comparison with the Non-TAG cohort showed comparable 2-year OS (59.4% vs 60.8%; p = 0.9). Frontline TAG was not associated with OS in pooled multivariable regression (HR 0.89 [0.37–2.15]; p = 0.803), while peripheral blood involvement remained associated with reduced OS (HR 2.63, 95% CI 1.1–6.27; p = 0.03). In this large multicenter real-world cohort, frontline TAG achieved high response rates with manageable toxicity. While unmeasured selection may contribute to the higher transplantation rate after TAG, durable remissions were achieved in patients undergoing post-TAG consolidation, supporting TAG as an induction and bridging strategy to allogeneic stem cell transplantation.