Outcomes of Tagraxofusp in Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN): A Multicenter Real-World Analysis

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 <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 >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.

Sauer:Abbvie: Other: financial support . Mikesch:Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel- & congress-support; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Astellas: Other: Travel- & congress-support; Novartis: Honoraria, Other: Travel- & congress-support; Otsuka: Membership on an entity's Board of Directors or advisory committees; BeiGene: Honoraria; Alexion: Membership on an entity's Board of Directors or advisory committees, Other: Travel- & congress-support; GSK: Membership on an entity's Board of Directors or advisory committees; Lab. Delbert: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Honoraria, Other: Travel- & congress-support; Celgene: Honoraria, Other: Travel- & congress-support; BMS: Honoraria; Servier: Honoraria. Gebauer:Janssen: Honoraria, Other: travel support; AstraZeneca: Honoraria; Beigene: Honoraria, Other: travel support ; Takeda: Honoraria; Menarini Stemline: Honoraria. Bröckelmann:Takeda: Consultancy, Honoraria, Research Funding; BMS: Honoraria, Research Funding; BeiGene: Honoraria, Research Funding; Merck Sharp & Dohme: Consultancy, Honoraria, Research Funding; Need Inc.: Consultancy, Current holder of stock options in a privately-held company; Stemline: Consultancy, Honoraria; Else-Kröner Fresenius Foundation: Other: Excellence Stipend. Buecklein:Otsuka: Consultancy; Pierre Fabre: Consultancy; Pfizer: Consultancy, Honoraria; Janssen: Research Funding; Takeda: Research Funding; BMS: Research Funding; Amgen: Consultancy, Honoraria; Novartis: Speakers Bureau; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding. Lenz:BeiGene: Honoraria; Lilly: Honoraria; AstraZeneca: Honoraria, Research Funding; Incyte: Honoraria; Amgen: Honoraria; BMS: Honoraria; Janssen: Honoraria, Research Funding; AbbVie, BeiGene, Sobi, Roche, Gilead, BMS: Other: Travel; Roche: Honoraria, Research Funding; AGIOS: Research Funding; Genmab: Honoraria; Immagene: Honoraria; MorphoSys: Honoraria, Research Funding; Roche, Gilead, BMS, Novartis, AstraZeneca, Abbvie, Incyte, Genmab, Constellation, ADC Therapeutics, Miltenyi, PentixaPharm, Sobi, Immagene, Genase, Hexal-Sandoz, Lilly, Beigene, MSD, Pierre Fabre: Membership on an entity's Board of Directors or advisory committees; Hexal/Sandoz: Honoraria; Celgene: Honoraria, Research Funding; Roche, Gilead, BMS, Novartis, AstraZeneca, Abbvie, Incyte, Genmab, Constellation, ADC Therapeutics, Miltenyi, PentixaPharm, Sobi, Immagene, Genase, Hexal-Sandoz, Lilly, Beigene, MSD, Pierre Fabre: Consultancy; AbbVie: Honoraria; Karyopharm: Honoraria; AQUINOX: Research Funding; Sobi: Honoraria, Speakers Bureau; Pierre Fabre: Honoraria; Acerta: Research Funding; ADC Therapeutics: Honoraria; Miltenyi Biotech: Honoraria; MSD: Honoraria; Constellation: Honoraria; Genase: Honoraria; ELVESCA: Current equity holder in private company; Gilead: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Verastem: Research Funding; Bayer: Honoraria, Research Funding; PentixaPharm: Honoraria; NanoString: Honoraria. Melchardt:Abbvie, Roche: Honoraria. Shumilov:Takeda: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Other: Travel and congress support; BMS: Consultancy, Honoraria; Incyte: Honoraria; Oncopeptides: Consultancy, Honoraria, Other: Travel and congress support; Stemline: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Other: Travel and congress support; Sanofi-Aventis: Consultancy, Honoraria, Other: Congress support.