Background: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive hematologic malignancy with historical overall survival (OS) of 8-14 months from diagnosis. Tagraxofusp is a targeted therapy directed to CD123. The US FDA has approved tagraxofusp for the treatment of BPDCN in adult and pediatric patients 2 years and older. CD123 is ubiquitously expressed at high levels on plasmacytoid dendritic cells (pDCs), the cell of origin of BPDCN, and targeting of CD123 with tagraxofusp resulted in high response rates, durable remissions, and a significant proportion of patients bridged to hematopoietic cell transplant (HCT) in first remission (45%). While HCT has the potential to prolong remission of patients with hematologic cancers, relapses after transplantation still occur in patients with certain risk factors including minimal residual disease (MRD). This study is designed to assess the safety and efficacy of tagraxofusp monotherapy as a maintenance treatment in patients with BPDCN post-HCT. The study is open for enrollment and expected to recruit approximately 20 patients. NCT04317781

Rationale: Available data suggest long-term remission can be expected in approximately 50% of patients with BPDCN that undergo allo-HCT. Accordingly, strategies are needed to further reduce the risk of relapse post-HCT.

Methods: The study is a Phase 2, single-center, open-label, single-arm clinical trial of tagraxofusp in patients with BPDCN that have undergone HCT. Planned enrollment is 20 patients. Treatment with tagraxofusp will be initiated between day 45 and 120 post-HCT, and dosed days 1-3 in cycles 1-4, and days 1-2 in cycles 5 and beyond. Each treatment cycle is 28 days. Duration of therapy for patients in complete response (CR) or clinical CR (CRc) post-transplant is 24 cycles, with patients who are MRD-positive or remain at high risk of relapse, eligible for continued treatment for as long as they derive benefit. In patients whose post-HCT disease status is either CR with incomplete blood count recovery (CRi) or partial response (PR), treatment will continue until disease progression or unacceptable toxicity.

Major Inclusion/Exclusion Criteria: Age ≥18; >30 days post-transplant without active or chronic infections; Karnofsky PS ≥60%; Lansky ≥60; adequate organ function including LVEF ≥ lower limit of normal (LLN); creatinine ≤1.5 mg/dL; albumin ≥3.2 g/dL; bilirubin ≤1.5 upper limit of normal (ULN); AST/ALT ≤2.5 times ULN; and ANC ≥1000. For allo-HCT, no ≥ grade 2 visceral (gut or liver) acute graft versus host disease (GVHD) and no ≥ grade 3 or any other acute GVHD (chronic GVHD allowed at investigator discretion). Key exclusions: Persistent clinically significant non-hematologic toxicities ≥ grade 2; CNS involvement; receiving chemotherapy, radiotherapy, or other anti-cancer therapy within 14 days of first dose of study drug; uncontrolled infection; HIV/Hepatitis B and/or C; and clinically significant cardiopulmonary disease.

Endpoints: Primary endpoints include safety and tolerability of tagraxofusp in patients with BPDCN post-HCT, with survival as secondary outcomes.


Bashir:Amgen: Other: Advisory Board; Purdue: Other: Advisory Board; Acrotech: Research Funding; StemLine: Research Funding; KITE: Other: Advisory Board; Takeda: Other: Advisory Board, Research Funding; Celgene: Research Funding. Shpall:Magenta: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Adaptimmune: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: Licensing Agreement; Zelluna: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Popat:Bayer: Research Funding; Novartis: Research Funding. Pemmaraju:Stemline Therapeutics: Honoraria, Research Funding; LFB Biotechnologies: Honoraria; Roche Diagnostics: Honoraria; Pacylex Pharmaceuticals: Consultancy; Blueprint Medicines: Honoraria; Samus Therapeutics: Research Funding; Novartis: Honoraria, Research Funding; Celgene: Honoraria; Plexxikon: Research Funding; Affymetrix: Other: Grant Support, Research Funding; AbbVie: Honoraria, Research Funding; Daiichi Sankyo: Research Funding; SagerStrong Foundation: Other: Grant Support; DAVA Oncology: Honoraria; MustangBio: Honoraria; Cellectis: Research Funding; Incyte Corporation: Honoraria. Champlin:Takeda: Patents & Royalties; Actinium: Consultancy; Omeros: Consultancy; Genzyme: Speakers Bureau; DKMS America: Membership on an entity's Board of Directors or advisory committees; Johnson and Johnson: Consultancy; Cytonus: Consultancy. Qazilbash:Bioline: Research Funding; Bioclinica: Consultancy; Amgen: Research Funding; Angiocrine: Research Funding; Janssen: Research Funding.

Author notes


Asterisk with author names denotes non-ASH members.

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