Tagraxofusp is a Novel Targeted Therapy Directed to CD123 - European Medical Journal
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Tagraxofusp is a Novel Targeted Therapy Directed to CD123

| Hematology
Authors:
*Naveen Pemmaraju,1 Andrew A. Lane,2 Kendra L. Sweet,3 Anthony S. Stein,4 Sumithira Vasu,5 David A. Rizzieri,6 Eunice S. Wang,7 Madeleine Duvic,1 Todd Rosenblat,8 Oleg Akilov,9 Jeffrey E. Lancet,3 Hagop M. Kantarjian,1 Marina Konopleva1
Disclosure:

Dr Pemmaraju reports receiving: consulting fees and honoraria from Celgene, Incyte, Roche Diagnostics; LFB, grant support, consulting fees, and honoraria from MustangBio and Novartis; and grant support from Samus Therapeutics, Cellectis, Plexxikon, Daiichi Sankyo, Affymetrix, and Patient Power.

Citation
EMJ Hematol. ;7[1]:44-45. AR No. AR1 .

Each article is made available under the terms of the Creative Commons Attribution-Non Commercial 4.0 License.

Blastic plasmocytoid dendritic cell neoplasm (BPDCN), a rare, highly aggressive haematologic malignancy, often with cutaneous and other extramedullary (e.g., lymph node, viscera) manifestations, is derived from plasmacytoid dendritic cells, which express high levels of CD123.1-3 BPDCN has historically carried a poor prognosis with median overall survival (mOS) ranging from 8–14 months from diagnosis.4 Tagraxofusp is a novel targeted therapy directed to CD123.5 In the largest prospectively designed study in patients with BPDCN to date, the efficacy and safety of tagraxofusp was evaluated in a nonrandomised, single-arm, multicentre study evaluating outcomes in both treatment-naïve and previously-treated patients with BPDCN.

Among the 29 treatment naïve patients treated with tagraxofusp (12 mcg/kg), a 90% overall response rate was demonstrated, in which the majority of responses were complete response (CR), clinical CR (CRc, defined as CR with residual skin abnormality not indicative of active disease). Furthermore, of note, 45% of patients were bridged to stem-cell transplantation, including older patients who might have been excluded from intensive therapy. At the time of the analysis (median follow-up of 25 months), the mOS had yet to be reached. The long-term survival probabilities reached 59% at 18 months and 52% at 24 months. Among the 15 patients with previously treated disease, the overall response rate was 67% (10/15), with meaningful mOS of 8.5 months.

Tagraxofusp has a demonstrated safety profile. The most common adverse reactions in patients with treatment-naïve or previously treated malignancies treated with tagraxofusp at the labelled dose and schedule included: also add decreases in albumin (77%), platelets (65%) and increases in alanine (82%) and aspartate (79%) aminotransferase levels. On the basis of this dataset, tagraxofusp is FDA-approved for treatment of adult and paediatric patients,6,7 aged 2 years and older, with BPDCN, and is commercially available in the USA. Tagraxofusp is the first and only approved treatment for BPDCN and the first approved CD123-targeted therapy. Tagraxofusp is additionally being clinically evaluated in other indications including chronic myelomonocytic leukaemia, myelofibrosis, acute myeloid leukaemia, and multiple myeloma.

References
Riaz W et al. Blastic plasmacytoid dendritic cell neoplasm: Update on molecular biology, diagnosis, and therapy. Cancer Control. 2014;21(4):279-89. Pemmaraju N. Novel pathways and potential therapeutic strategies for blastic plasmacytoid dendritic cell neoplasm (BPDCN): CD123 and beyond. Curr Hematol Malig Rep. 2017;12(6):510-2. Pemmaraju N, Konopleva M. Treating blastic plasmacytoid dendritic cell neoplasm. Ask the Hematologist. 2018;15(5). Pagano L et al. Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation: An Italian multicenter study Haematologica. 2013;98(2):239-46. Pemmaraju N et al. Tagraxofusp in blastic plasmacytoid dendritic-cell neoplasm. N Engl J Med. 2019;380(17):1628-37. Stemline Therapeutics. FDA approves ELZONRISTM (tagraxofusp), the first treatment for blastic plasmacytoid dendritic cell neoplasm and first CD123-targeted therapy. Available at: https://ir.stemline.com/node/10281/pdf. Last accessed: 01 July 2019. Stemline Therapeutics. Stemline Therapeutics receives breakthrough therapy designation from U.S. Food and Drug Administration forSL-401. Available at: https://ir.stemline.com/static-files/9e132f92-ade1-4770-9e9e-5e24e199c74d. Last accessed: 01 July 2019.