Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) in Pediatric Patients with Tagraxofusp, a CD123-Targeted Therapy
Authors: Pemmaraju Naveen , Cuglievan Branko , Lasky Joseph L , Kheradpour Albert , Hijiya Nobuko , Stein Anthony S. , Pawlowska Anna B 
Published: November 2021

Abstract
BACKGROUND
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and clinically aggressive hematological malignancy that overexpresses CD123, the interleukin-3 (IL3) receptor alpha subunit. Although BPDCN predominantly affects older adults (median age of 65 years at diagnosis), cases of BPDCN have been reported across all age groups, including infants and children. There is limited data available in the literature on the efficacy and safety of treatments for pediatric patients with BPDCN. Tagraxofusp (TAG, SL-401) is a CD123-directed targeted therapy consisting of recombinant human IL3 linked to a truncated diphtheria toxin payload. A published multicohort prospective study, with prespecified multisystem endpoints, demonstrated the benefit of TAG in adult patients with untreated or relapsed BPDCN. Among the untreated patients, 72% had a complete response and 90% overall response rate; of these patients, 45% were bridged to stem cell transplantation. Adverse events included transaminase elevations, hypoalbuminemia, thrombocytopenia, and capillary leak syndrome (CLS). In a previous case report including 3 pediatric patients with BPDCN, TAG was well-tolerated without significant toxicities and showed encouraging initial clinical responses. TAG was FDA approved in 2018 for BPDCN treatment in adult and pediatric (≥2 years) patients and was recently approved in the EU as monotherapy for first-line treatment in adults.

METHODS
Here, we report on a multicenter, retrospective case series investigation involving pediatric patients diagnosed with BPDCN at 3 centers in the United States. All patients were treated with TAG according to local institutional guidelines as either first-line treatment (1L) or as a therapy for relapsed/refractory disease (R/R). Data was collected retrospectively via chart review and summarized descriptively. Assessments included tumor response to therapy, survival and safety (adverse events and laboratory abnormalities).

RESULTS
A total of 6 pediatric patients diagnosed with BPDCN and treated with TAG were included in this analysis. The median age for patients in this study was 15.5 years (range 10 - 21 years), and 4 of the 6 patients were female. Three patients were R/R and received systemic therapy prior to TAG administration, while 3 patients were treatment-naive. Four patients had bone marrow involvement, 2 patients had lymph node involvement, and all 6 patients had skin lesions at diagnosis. All patients received a TAG dose of 12 mcg/kg, with the exception of 1 patient who received 9 mcg/kg. At the time of data cut off, the number of cycles administered ranged from 1 to 4. TAG was well tolerated in these 6 patients. One patient experienced headaches, hot flashes, fatigue, and mouth sores, and low albumin was observed in one patient. No other adverse events were reported and CLS was not observed in these patients. One patient had a complete response to TAG therapy (bone marrow minimal residual disease negative), 2 patients had stable disease, and 3 patients did not have an observed response. In the three 1L patients, one patient had stable disease (no progression after 4 TAG cycles), and 1 patient with extensive disease (skin, bone marrow and central nervous system) had a complete response. Three patients bridged to a stem cell transplant (SCT); 2 were R/R and 1 was 1L. Median survival data for this cohort will be presented (5 of 6 patients remain alive).

CONCLUSIONS
This multicenter, retrospective case series of 6 pediatric patients with BPDCN expands our base of knowledge of BPDCN treatment in younger individuals. At the time of data cut off for this abstract, TAG, an approved treatment for BPDCN, was well tolerated in all patients. Treatment with TAG was associated with promising efficacy, including half of the patients with responses that allowed for bridging to SCT.

Disclosures
Pemmaraju: CareDx, Inc.: Consultancy; Plexxicon: Other, Research Funding; Samus: Other, Research Funding; ASH Communications Committee: Membership on an entity's Board of Directors or advisory committees; Aptitude Health: Consultancy; Springer Science + Business Media: Other; HemOnc Times/Oncology Times: Membership on an entity's Board of Directors or advisory committees; Blueprint Medicines: Consultancy; Bristol-Myers Squibb Co.: Consultancy; Dan's House of Hope: Membership on an entity's Board of Directors or advisory committees; ASCO Leukemia Advisory Panel: Membership on an entity's Board of Directors or advisory committees; Sager Strong Foundation: Other; Cellectis S.A. ADR: Other, Research Funding; Daiichi Sankyo, Inc.: Other, Research Funding; DAVA Oncology: Consultancy; Roche Diagnostics: Consultancy; MustangBio: Consultancy, Other; Abbvie Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; Celgene Corporation: Consultancy; Stemline Therapeutics, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; LFB Biotechnologies: Consultancy; Clearview Healthcare Partners: Consultancy; Protagonist Therapeutics, Inc.: Consultancy; Affymetrix: Consultancy, Research Funding; Incyte: Consultancy; Novartis Pharmaceuticals: Consultancy, Other: Research Support, Research Funding; ImmunoGen, Inc: Consultancy; Pacylex Pharmaceuticals: Consultancy. Hijiya: Novartis: Consultancy; Stemline Therapeutics: Consultancy. Stein: Amgen: Consultancy, Speakers Bureau; Celgene: Speakers Bureau; Stemline: Speakers Bureau.