Real world (RW) study of patients (pts) with relapsed or refractory (RR) blastic plasmacytoid dendritic cell neoplasm (BPDCN) treated with tagraxofusp (TAG).
Authors: Herling Marco , Angelucci Emanuele , Manteigas David , Zuurman Michael , Deconinck Eric 
Published: June 2024

e18533 Background: BPDCN is characterized by clonal expansion of plasmacytoid dendritic malignant cells that express CD123 and other markers. TAG, a CD123-directed therapy, is the only drug approved to treat BPDCN (US/EU). In August 2019, a European Named Patient Program (NPP) started to ensure pt access to TAG. To assess RW safety and efficacy of TAG treatment in RR BPDCN, a pt population with a very poor prognosis, we retrospectively analyzed data from pts enrolled in the NPP. Methods: Pts with RR BPDCN received TAG 12 mcg/kg qd on days 1-5 (or by day 10) of each 21-day cycle. The first TAG cycle was given inpatient with outpatient treatment allowed thereafter. Clinicians received training on capillary leak syndrome (CLS) monitoring and management guidelines. Primary endpoints were complete response (CR) after 2-3 cycles and CLS incidence and grade (G). Secondary endpoints included number of pts bridged to stem cell transplantation (SCT), progression-free survival (PFS), overall survival (OS), best overall response rate (ORR), duration of response (DOR), and safety. Results: Of 18 pts with RR BPDCN (median age 66 y [29–83]; 89% male), 67% had received 1 prior line of therapy and 28% 2 prior lines. At initial diagnosis, pts had disease involvement in bone marrow (89%), skin (67%), and lymph nodes (61%). Median time from initial diagnosis to TAG was 7.4 mo (1–27). At a median follow-up of 8 mo, pts received a median of 2 (1–5) TAG cycles. In 15 pts with ≥1 tumor assessment, the ORR was 67% (40% CR and 27% partial response [PR]) with a median DOR of 5 mo (95% CI, 3.0–not estimable [NE]). All 18 pts had a median PFS of 4.3 mo (95% CI, 1.4–12.9) and median OS of 8.6 mo (95% CI, 3.6–NE). In 15 pts with ≥1 tumor assessment, 6 (40%) pts were bridged to SCT and had durable posttransplant responses (CR 83%; PR 17%) with median DOR, PFS, and OS not reached. CLS was mostly mild to moderate in severity; 61% of pts had CLS in cycle 1 and only 1 pt had an event in cycle 2. The median time to CLS resolution was 4 days. Other than CLS, TAG-related nonhematologic G3-4 adverse events (AEs) and serious AEs (SAEs) occurred in 44% of pts, all during cycle 1, with hepatic cytolysis, pneumonia and tumor lysis syndrome reported in 2 (11%) pts each. Grade 3-4 thrombocytopenia and pancytopenia were reported in 2 (11%) pts each. Median time to resolution was 5 days for the nonhematologic G3-4 AEs/SAEs and 18 days for thrombocytopenia. Two (11%) pts had G3-4/SAE infections. There were no treatment-related deaths. Conclusions: TAG induced fast and durable responses, and a high response rate, in RR BPDCN pts, with prolonged survival in a poor prognosis population, where historic treatments show limited efficacy. There were no new safety signals. With proper selection, monitoring, and directed intervention, CLS is manageable, usually mild, limited to the first cycle, and does not recur. These RW results support the use of TAG in pts with RR BPDCN.