Abstract
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive, orphan hematologic malignancy that expresses CD123 and frequently presents in skin, bone marrow, blood, and viscera. Tagraxofusp is a first-in-class CD123-targeted therapy and the only US-approved drug to treat BPDCN. Approval was based on a pivotal, multicenter, phase II study (NCT02113982), the largest prospective BPDCN trial to date, in which tagraxofusp monotherapy demonstrated durable clinical responses across treatment-naive and relapsed/refractory BPDCN, and often resulted in patients proceeding to stem cell transplant following tagraxofusp-induced remissions. Advanced practitioners (APs) are critical in providing comprehensive and consistent monitoring, supportive care management for adverse events, and patient education. A core specialized interdisciplinary team coupled with AP-led management optimizes tagraxofusp treatment. This paper reviews best practices for the clinical management of patients with BPDCN receiving tagraxofusp in the context of the US package insert and APs’ real-world management approaches.
References
Angelucci, E., Deconinck, E., Manteigas, D., Zuurman, M., & Herling, M. (2023). Durable outcomes with manageable safety leading to prolonged survival with tagraxofusp for treatment-naive patients with blastic plasmacytoid dendritic cell neoplasm: Updated results from a European named patient program. Blood, 142(Suppl 1), 547–548. https://doi.org/10.1182/blood-2023-178734
Bruinooge, S. S., Pickard, T. A., Vogel, W., Hanley, A., Schenkel, C., Garrett-Mayer, E., Tetzlaff, E., Rosenzweig, M., Hylton, H., Westin, S. N., Smith, N., Lynch, C., Kosty, M. P., & Williams, S. F. (2018). Understanding the role of advanced practice providers in oncology in the United States. Journal of Oncology Practice, 14(9), e518–e532. https://doi.org/10.1200/JOP.18.00181
ClinialTrials.gov. (2025). Study of Venetoclax, a BCL2 Antagonist, for Patients With Blastic Plasmacytoid Dendritic Cell Neoplasm. https://clinicaltrials.gov/study/NCT03485547
ClinicalTrials.gov. (2025). Clinical Trial of CD123-targeted CAR-NK Therapy for Relapse/refractory AML or BPDCN. https://clinicaltrials.gov/study/NCT06690827
ClinicalTrials.gov. (2025). Study of IMGN632 in Patients With Untreated BPDCN and Relapsed/Refractory BPDCN. https://clinicaltrials.gov/study/NCT03386513
ClinicalTrials.gov. (2025). First-in-human Study of SAR443579 Infusion in Male and Female Children and Adult Participants With Relapsed or Refractory Acute Myeloid Leukemia (R/R AML), B-cell Acute Lymphoblastic Leukemia (B-ALL), High Risk-myelodysplasia (HR-MDS), or Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN). https://clinicaltrials.gov/study/NCT05086315
ClinicalTrials.gov. (2025). SL-401 in Combination With Azacitidine or Azacitidine/Venetoclax in Acute Myeloid Leukemia (AML), High-Risk Myelodysplastic Syndrome (MDS) or Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN). https://clinicaltrials.gov/study/NCT03113643
ClinicalTrials.gov. (2025). Venetoclax, SL-401, and Chemotherapy for the Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm. https://clinicaltrials.gov/study/NCT04216524
Herling, M., Angelucci, E., Manteigas, D., Zuurman, M., & Deconinck, E. (2024). Real-world study of patients with relapsed or refractory blastic plasmacytoid dendritic cell neoplasm treated with tagraxofusp. HemaSphere, 8(Suppl 1), e104. https://doi.org/10.1002/hem3.104
Jen, E. Y., Gao, X., Li, L., Zhuang, L., Simpson, N. E., Aryal, B., Wang, R., Przepiorka, D., Shen, Y. L., Leong, R., Liu, C., Sheth, C. M., Bowen, S., Goldberg, K. B., Farrell, A. T., Blumenthal, G. M., & Pazdur, R. (2020). FDA approval summary: Tagraxofusp-erzs for treatment of blastic plasmacytoid dendritic cell neoplasm. Clinical Cancer Research, 26(3), 532–536. https://doi.org/10.1158/1078-0432.CCR-19-2329
Luskin, M. R., & Lane, A. A. (2024). Tagraxofusp for blastic plasmacytoid dendritic cell neoplasm. Haematologica, 109(1), 44–52. https://doi.org/10.3324/haematol.2022.282171
Martín-Martín, L., López, A., Vidriales, B., Caballero, M. D., Rodrigues, A. S., Ferreira, S. I., Lima, M., Almeida, S., Valverde, B., Martínez, P., Ferrer, A., Candeias, J., Ruíz-Cabello, F., Buadesa, J. M., Sempere, A., Villamor, N., Orfao, A., & Almeida, J. (2015). Classification and clinical behavior of blastic plasmacytoid dendritic cell neoplasms according to their maturation-associated immunophenotypic profile. Oncotarget, 6(22), 19204–19216. https://doi.org/10.18632/oncotarget.4146
Mirrakhimov, A. E., Voore, P., Khan, M., & Ali, A. M. (2015). Tumor lysis syndrome: A clinical review. World Journal of Critical Care Medicine, 4(2), 130–138. https://doi.org/10.5492/wjccm.v4.i2.130
Pagano, L., Valentini, C. G., Pulsoni, A., Fisogni, S., Carluccio, P., Mannelli, F., Lunghi, M., Pica, G., Onida, F., Cattaneo, C., Piccaluga, P. P., Di Bona, E., Todisco, E., Musto, P., Spadea, A., D’Arco, A., Pileri, S., Leone, G., Amadori, S., Facchetti, F.,…GIMEMA-ALWP (Gruppo Italiano Malattie EMatologiche dell’Adulto, Acute Leukemia Working Party). (2013). Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation: An Italian multicenter study. Haematologica, 98(2), 239–246. https://doi.org/10.3324/haematol.2012.072645
Pemmaraju, N., Lane, A. A., Sweet, K. L., Stein, A. S., Vasu, S., Blum, W., Rizzieri, D. A., Wang, E. S., Duvic, M., Sloan, J. M., Spence, S., Shemesh, S., Brooks, C. L., Balser, J., Bergstein, I., Lancet, J. E., Kantarjian, H. M., & Konopleva, M. (2019). Tagraxofusp in blastic plasmacytoid dendritic-cell neoplasm. The New England Journal of Medicine, 380(17), 1628–1637. https://doi.org/10.1056/NEJMoa1815105
Pemmaraju, N., Wilson, N. R., Khoury, J. D., Jain, N., Daver, N., Pierce, S., Jabbour, E., Kadia, T., DiNardo, C., Garcia-Manero, G., Qazilbash, M., Konopleva, M., & Kantarjian, H. (2021). Central nervous system involvement in blastic plasmacytoid dendritic cell neoplasm. Blood, 138(15), 1373–1377. https://doi.org/10.1182/blood.2021011817
Pemmaraju, N., Sweet, K. L., Stein, A. S., Wang, E. S., Rizzieri, D. A., Vasu, S., Rosenblat, T. L., Brooks, C. L., Habboubi, N., Mughal, T. I., Kantarjian, H., Konopleva, M., & Lane, A. A. (2022). Long-term benefits of tagraxofusp for patients with blastic plasmacytoid dendritic cell neoplasm. Journal of Clinical Oncology, 40(26), 3032–3036. https://doi.org/10.1200/JCO.22.00034
Pemmaraju, N., Kantarjian, H., Sweet, K., Wang, E., Senapati, J., Wilson, N. R., Konopleva, M., Frankel, A. E., Gupta, V., Mesa, R., Ulrickson, M., Gorak, E., Bhatia, S., Budak-Alpdogan, T., Mason, J., Garcia-Romero, M. T., Lopez-Santiago, N., Cesarman-Maus, G., Vachhani, P., Lee, S.,…Lane, A. A. (2023). North American blastic plasmacytoid dendritic cell neoplasm consortium: Position on standards of care and areas of need. Blood, 141(6), 567–578. https://doi.org/10.1182/blood.2022017865
Pemmaraju, N., Madanat, Y. F., Rizzieri, D., Fazal, S., Rampal, R., Mannis, G., Wang, E. S., Foran, J., & Lane, A. A. (2024a). Treatment of patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN): Focus on the use of tagraxofusp and clinical considerations. Leukemia & Lymphoma, 65(5), 548–559. https://doi.org/10.1080/10428194.2024.2305288
Pemmaraju, N., Deconinck, E., Mehta, P., Walker, I., Herling, M., Garnache-Ottou, F., Gabarin, N., Campbell, C. J. V., Duell, J., Moshe, Y., Mughal, T., Mohty, M., & Angelucci, E. (2024b). Recent advances in the biology and CD123-directed treatment of blastic plasmacytoid dendritic cell neoplasm. Clinical Lymphoma, Myeloma & Leukemia, 24(4), e130–e137. https://doi.org/10.1016/j.clml.2023.12.010
Rivoli, G., Beltrami, G., Raiola, A., Dominietto, A., Riggi, M., & Angelucci, E. (2022). Tagraxofusp in blastic plasmacytoid dendritic cell neoplasm with/without central nervous system involvement and intrathecal chemotherapy as primary treatment or prophylaxis: An Italian experience. HemaSphere, 6(S3), 828–829. https://doi.org/10.1097/01.HS9.0000845008.01963.5f
Stemline Therapeutics, Inc. (2023). Elzonris (tagraxofusp-erzs) injection package insert. https://rxmenarinistemline.com/ELZONRIS_US_Full_Prescribing_Information.pdf
