Outcomes in patients (pts) younger than 50 years old (yo) with treatment-naïve blastic plasmacytoid dendritic cell neoplasm (BPDCN) treated with tagraxofusp (TAG): Subanalysis of a phase 1/2 trial.

6518 Background: BPDCN is an aggressive, orphan hematologic malignancy characterized by cells expressing CD123 and other markers. In BPDCN pts <50 yo, including in the adolescent and young adult (AYA) population (ie, pts 15-39 yo), data are limited. TAG, a first-in-class CD123-targeted therapy, is the only drug approved for adults (US/EU) and pediatric pts aged ≥2 yo (US only) with BPDCN. TAG has a well-characterized and manageable safety profile, with transient adverse events (AEs) occurring mostly in cycle 1, no cumulative long-term toxicity, and no myelosuppression. While not approved, multi-agent chemotherapy is used in AYAs, resulting in short- and long-term toxicity, including myelosuppression. Here we report the safety and efficacy of 1L TAG treatment, with prespecified/multi-system response criteria, for BPDCN pts <50 yo from a subgroup analysis of the phase 1/2 TAG monotherapy study (NCT02113982). Methods: We analyzed outcomes in treatment-naïve pts <50 yo who received 1L TAG 12 µg/kg intravenously on days 1-5 of a 21-day cycle. Assessed outcomes included best response, time to best response, duration of response (DOR), overall survival (OS), treatment-related adverse events (TRAEs), and capillary leak syndrome (CLS). Results: Ten pts (median age of 31.5 yo [range 22-45]) were included in this analysis, including 6 AYA pts. All pts had ECOG PS of 0-1, 20% had bone marrow involvement, and 60% had ≥2 sites of BPDCN disease. Pts received a median of 4 cycles (range 2-7) of TAG. In cycle 1, pts received a median of 5 TAG doses (range 3-5) in line with the USPI dosing. At a median follow-up of 34 months, the CR/CRc rate was 70%, with a 41-day median time to CR/CRc. DOR was not reached (range 8.4-51.8 months); median OS was 38.4 months. All pts were bridged to stem cell transplantation (SCT), including 2 autologous SCTs: 7 pts with CR/CRc following TAG treatment (median time from last TAG dose to SCT, 38 days) and 3 pts with PR or SD were bridged to SCT following subsequent multi-agent chemotherapy. Most common Grade 3-4 TRAEs were thrombocytopenia and ALT/AST elevation; the majority of TRAEs resolved with resolution in the same cycle; no grade 5 TRAEs occurred. No pts had a dose reduction or discontinuation due to a TRAE. No investigator-assessed CLS was reported, although some pts required dose interruption due to weight gain or hypoalbuminemia. Conclusions: In treatment-naïve BPDCN pts <50 yo, including AYAs, TAG, a chemotherapy-free option, induced high rates of CR/CRc (70%) and allowed all pts who achieved CR/CRc to bridge to SCT. TAG was well tolerated with no cumulative AEs or cumulative myelosuppression. No investigator-assessed CLS was observed in these younger pts. Overall, TAG is an effective front-line therapy, including in pts <50, with durable (median not reached) responses and prolonged survival. Clinical trial information: NCT02113982 .