Outcomes of Tagraxofusp in Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN): A Multicenter Real-World Analysis
Authors: Berning Philipp , Baden David , Faustmann Philipp , Janjetovic Snjezana , Zieger Hanna Katharina , Schroeder Jan Christian , Velazquez Giuliano Filippini , Ossami Saidy Anna , Boyadzhiev Hristo , Sauer Tim , Mikesch Jan-Henrik , Gebauer Niklas , Ghandili Susanne , Bröckelmann Paul J. , Hildebrand Friederike , Buecklein Veit L. , Wurm-Kuczera Rebecca , Keller Ulrich , Lenz Georg , Pabst Thomas , Melchardt Thomas , Lengerke Claudia , Hanoun Maher , Shumilov Evgenii , Bacher Ulrike 
Published: December 2024

Introduction
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive hematological malignancy derived from plasmacytoid dendritic cells. The approval of Tagraxofusp (TAG) in 2018 has shifted treatment paradigms, offering a targeted option for induction therapy in BPDCN, especially for patients (pts) ineligible for an intensive chemotherapy. While TAG has shown promising results with a 75% overall response rate (ORR), the role of consolidation treatments in the TAG era remains to be determined. Historically, long-term disease control has been achieved through allogeneic stem cell transplantation (allo-SCT), but its optimal timing and patient selection in the context of TAG therapy remain unclear. There is a need for real-world data to better understand efficacy and outcomes of these treatment approaches in clinical routine.
Methods
We conducted a multicenter retrospective analysis including 32 pts treated with TAG as first-line treatment for BPDCN in 12 German/Austrian/Swiss tertiary centers between November 2019 and March 2024. Outcome was calculated from the day of first application of TAG until the respective event. Using a historical cohort of 40 BPDCN pts not treated with TAG, propensity score matching (nearest neighbor 1:1 matching with a caliper of 0.2 standard deviations, for age at diagnosis, number of therapy lines, use of auto-SCT as well as exact matching for allo-SCT as co-variates) was performed to compare outcomes and the role of consolidative allo-SCT between both groups.
Results
We identified 32 pts (84.4% male) with a median age of 71.5 years (range: 24-87) at diagnosis. ECOG performance score &lt;2 was noted in 90.0% of cases. Disease manifestations included skin (93.8%), peripheral blood (84.4%), lymphadenopathy (56.3%), bone marrow (56.7%), hepatosplenomegaly (50.0%) and CNS (16.1%). The median time-to-TAG after BPDCN diagnosis was 20.5 days (range: 3-262), median number of TAG cycles was 2.5, and 74.2% of pts completed all planned administrations of the first cycle. Notable adverse events included tumor lysis syndrome (CTCAE≥3) in 9 pts (28.1%), and capillary leak syndrome in 8 pts (25.0%). During TAG treatment, 73.3% pts required albumin substitution and 75.9% steroid application. 15 pts (46.9%) underwent allo-SCT for consolidation, no auto-SCT was performed. Among allo-SCT recipients, 6/15 received myeloablative conditioning, 10/15 had TBI-based protocols, and 12/15 were transplanted from matched donors.
ORR after TAG was 82.7% with a median response duration of 5.0 months (range 0.23-50.5). With a median follow-up of 11.1 months (range 2.1-50.5), the 1-year progression-free survival (PFS) and overall survival (OS) rates were 40.8% and 67.0%, respectively. The cumulative 1-year relapse incidence was 50.0%, while non-relapse mortality (NRM) was 9.5%. Multivariate regression analysis, including age and TAG response as covariates, revealed that consolidative allo-SCT was significantly associated with improved PFS rates with median PFS of 3.0 months (95% CI: 2.1-6.1) vs. not reached (95% CI: 22.7-NA, HR=0.06, 95% CI: 0.01-0.46, p=0.006). Propensity score matching identified 20 pair-matched pts from the historical non-TAG cohort, of which 8 with allo-SCT. While 1-year OS rates were comparable between the matched TAG (58.3%) and matched non-TAG cohort (58.7%, p=0.96), allo-SCT consolidation was associated with improved OS (HR=0.16, 95% CI: 0.05-0.50, p=0.002) irrespective of induction treatment.
Conclusions
Our real-world data highlight the efficacy of Tagraxofusp in BPDCN, with a response rate of &gt;80%. Consolidation with allo-SCT significantly improved survival outcomes. Yet, survival was similar with prior TAG and conventional induction when consolidative allo-SCT was performed. These findings underscore the role of TAG as a bridge to allo-SCT and the importance of allo-SCT in maintaining durable remissions in the TAG era. Future studies are essential to optimize treatment strategies, identify prognostic factors, and improve long-term outcomes for BPDCN pts.