Introduction:Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, clinically aggressive hematologic malignancy that commonly involves four major compartments: cutaneous, bone marrow/blood, lymph nodes, and central nervous system (CNS). Tagraxofusp (TAG) is a first-in-class therapy directed to CD123, a target expressed in BPDCN, and is the only drug approved to treat BPDCN in the US and EU. TAG has demonstrated high rates of durable response and bridge to allogeneic hematopoietic cell transplantation (allo-HCT)(Pemmaraju N et al NEJM 2019). Historically, patients that undergo allogeneic allo-HCT have been reported to have long-term remissions, particularly if transplanted while in complete response; however, ~50% of patients will relapse post-allo-HCT, and strategies are needed to minimize this risk. No clinical studies to date have been conducted to assess the rate of post-HCT relapse in patients who receive TAG maintenance therapy after allo-HCT. This case study reports on a patient who was successfully treated with TAG therapy after allo-HCT in a phase 2 trial (NCT04317781).

Methods and Results: A 68-year-old woman with BPDCN underwent allo-HCT and was enrolled in a TAG post-allo-HCT maintenance trial at the MD Anderson Cancer Center in 2021. Therapy prior to allo-HCT included hydroxyurea and TAG + venetoclax + mini-HyperCVAD for 5 cycles. The patient was in morphologic complete remission with low positivity by flow cytometry (positive for minimal residual disease [MRD]) at the time of allo-HCT. After allo-HCT and prior to TAG maintenance therapy, the patient had persistent cytogenic abnormalities on a bone marrow next-generation sequencing (NGS) panel. The patient received TAG 9 mcg/kg for 3 days on a 28-day cycle after allo-HCT.

The patient received TAG in the post-allo-HCT setting for a total of 16 cycles. At mid-treatment (post Cycle 6, prior to Cycle 7) with TAG, the disease was in complete remission, and the bone marrow NGS panel was negative for mutations (MRD negative). The patient did not experience any high-grade toxicity or capillary leak syndrome (CLS); the only toxicity observed was weight gain (Grade 0 per CTCAE), TAG was stopped for that cycle, and the event resolved. After Cycle 16, the patient withdrew consent due to the burden of traveling from another state. Bone marrow NGS testing was repeated prior to discontinuing study treatment, and the panel remained negative for MRD, with disease still in complete remission.

Conclusions: This case report demonstrates a patient experiencing a clinically meaningful benefit with TAG maintenance therapy after allo-HCT. Both prolonged survival and manageable safety, in this case, highlight the feasibility of long-term TAG maintenance post-allo-HCT to control BPDCN.

Bashir:Pfizer: Research Funding; Stemline: Research Funding; Acrotech: Research Funding; GSK: Research Funding. Konopleva:Abbvie, Allogene Therapeutics, Cellectis, Forty Seven, Gilead Sciences, Genentech, Sanofi, MEI Pharma, Rafael Pharmaceuticals, Daiichi Sankyo Pharmaceutical, AstraZeneca Co., Menarini, Precision BioSciences.: Research Funding; Reata Pharmaceuticals.: Current holder of stock options in a privately-held company, Patents & Royalties; AbbVie, Forty Seven, Precision Biosciences, Gilead Sciences, Genentech, Janssen, Sanofi, MEI Pharma, Daiichi Sankyo Pharmaceutical, AstraZeneca Co., Menarini.: Consultancy. Srour:Orca Bio: Research Funding. Nieto:Astra Zeneca: Research Funding; Secura Bio: Research Funding; Affimed: Research Funding. Champlin:Orca Bio: Consultancy; Takeda Corporation: Patents & Royalties; Cell Source: Research Funding; Johnson & Johnson/Janssen: Consultancy; Actinium Pharmaceuticals: Consultancy; Omeros: Consultancy; Arog: Consultancy; Kadmon: Consultancy. Shpall:Syena: Other: License agreement; NY Blood Center: Membership on an entity's Board of Directors or advisory committees; Adaptimmune: Membership on an entity's Board of Directors or advisory committees; Axio: Membership on an entity's Board of Directors or advisory committees; Celaid Therapeutics: Membership on an entity's Board of Directors or advisory committees; Fibrobiologics: Membership on an entity's Board of Directors or advisory committees; Navan: Membership on an entity's Board of Directors or advisory committees; Affimed: Other: License agreement; Takeda: Other: License agreement. Qazilbash:Amgen: Research Funding; Bioline: Other: Advisory board; Janssen: Research Funding; NexImmune: Research Funding; Angiocrine: Research Funding. Pemmaraju:ASH Committee on Communications: Other: Leadership; PeerView Institute for Medical Education: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Physician Education Resource (PER): Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Dan's House of Hope: Membership on an entity's Board of Directors or advisory committees; Aplastic Anemia & MDS International Foundation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CancerNet: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CareDx: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Dava Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Harborside Press: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Imedex: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Intellisphere: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Patient Power: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; OncLive: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Menarini Group: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Medscape: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Magdalen Medical Publishing: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pacylex: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Cimeio Therapeutics AG: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ClearView Healthcare Partners: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CTI BioPharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ImmunoGen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Neopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSA Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Curio Science: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Stemline: Consultancy, Membership on an entity's Board of Directors or advisory committees; Protagonist Therapeutics, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; PharmaEssentia: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ASCO Cancer.Net Editorial Board: Other: Leadership; Karger Publishers: Other: Licenses; National Institute of Health/National Cancer Institute (NIH/NCI): Research Funding; United States Department of Defense (DOD): Research Funding; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Blueprint: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Aptitude Health: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; HemOnc Times/Oncology Times: Other: Uncompensated; Bristol Myers Squibb Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

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2023
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