Tagraxofusp Maintenance Post-Hematopoietic Stem Cell Transplantation Provides Long-Term Survival and Manageable Safety for a Patient with Blastic Plasmacytoid Dendritic Cell Neoplasm

Abstract

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.