Tagraxofusp, the first CD123-targeted therapy and first targeted treatment for blastic plasmacytoid dendritic cell neoplasm

ABSTRACT

Introduction: CD123 or interleukin 3 receptor alpha is overexpressed in multiple hematologic malignancies. Tagraxofusp is an intravenously administered CD123-directed cytotoxin consisting of the fusion of interleukin-3 with a truncated diphtheria toxin payload and was recently approved by the Food and Drug Administration for the treatment of adults and children aged 2 and older with blastic plasmacytoid dendritic cell neoplasm (BPDCN).

Areas Covered: In this review, we discuss the use of tagraxofusp in BPDCN, and active clinical trials involving this agent in several hematologic malignancies are also presented. Tagraxofusp has significant efficacy in patients with BPDCN and manageable safety profile, with the most commonly reported adverse events being asymptomatic elevation of alanine and aspartate aminotransferase levels, hypoalbuminemia, peripheral edema, and thrombocytopenia. The most serious side effect is capillary leak syndrome that can be lethal in some cases but the risk may be mitigated by early recognition and intervention.

Expert Opinion: Tagraxofusp has been introduced as a novel treatment of BPDCN, a rare hematologic malignancy, for which no standard therapy previously existed. Many patients treated with this agent were able to be bridged to stem cell transplantation, including older patients. In the future, combinations of tagraxofusp with other targeted agents will be explored.

KEYWORDS:

• Tagraxofusp
• BPDCN
• CD123
• leukemia

Article Highlights

• CD123 is a marker overexpressed in many hematologic malignancies

• Tagraxofusp is the first CD123-targeted agent that was approved by the FDA for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN).

• In a pivotal study of tagraxofusp in patients with BPDCN, great efficacy and manageable safety profile of this medication were demonstrated.

• Most important side effect is capillary leak syndrome that can present with hypoalbuminemia, edema, weight gain, and hypotension. High suspicion and close clinical monitoring are required.

• In the future, combination of tagraxofusp with other targeted therapies will be studied in patients with BPDCN.

Declaration of interest

D McCue: Consulting/honorarium: Stemline. AA Lane: Consulting/honorarium: N-of-One. Research funding: AbbVie, Stemline. N Pemmaraju: Consulting/honorarium: Celgene; Stemline; Incyte; Novartis; MustangBio; Roche Diagnostics, LFB Research funding/clinical trials support: Stemline; Novartis; Abbvie; Samus; Cellectis; Plexxikon; Daiichi-Sankyo; Affymetrix, SagerStrong Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they published a manuscript using SL-401 (now called Tagraxofusp) to assess its toxicity against blastic plasmacytoid dendritic cell neoplasm (BPDCN) in vitro and in a mouse xenograft model (Angelot-Delettre F et al., Haematologica. 2015, PMID: 25,381,130). The reviewer states they regularly use this drug as a positive cytotoxic control for blastic plasmacytoid dendritic cell neoplasm (Philippe L et al., Haematologica. 2017, PMID: 28,798,071). However, they were not aware of this current manuscript before accepting to review it. They also confirm that they did not receive any financial advantage from the company (Stemline Therapeutics, Inc) developing tagraxofusp.

Stemline Therapeutics, Inc provided a scientific accuracy review at the request of the journal editor.

Additional information

Funding

This research is supported in part by the M. D. Anderson Cancer Center Support Grant [P30 CA016672].