Tagraxofusp: efficacy, safety and unanswered questions


Tagraxofusp, the first and only FDA-approved drug for blastic plasmacytoid dendritic cell neoplasm (BPDCN), outperforms traditional chemotherapy treatment for the rare myeloid malignancy.

Tagraxofusp, the first and only FDA-approved drug for blastic plasmacytoid dendritic cell neoplasm (BPDCN), outperforms traditional chemotherapy treatment for the rare myeloid malignancy. But Grade 3 and higher adverse events are common with its use, and questions remain, including whether tagraxofusp might more effectively treat BPDCN when combined with other therapies, French researchers report in a review article published June 9 in OncoTargets and Therapy.1

Tagraxofusp (ELZONRIS, Stemline) is a CD123-directed cytotoxin approved for BPDCN treatment in patients 2 years and older. CD123 is among the major therapeutic targets of new and pipeline therapies to treat myeloid cancers.

“CD123, the α-subunit of interleukin (IL)-3 receptor, is constantly overexpressed at the surface of tumoral cells,” the authors wrote. “Tagraxofusp (or SL-401) is a recombinant cytotoxin which consists of human interleukin-3 fused to a truncated diphtheria toxin.”

In essence, it binds to CD123 at the cells’ surface. The diphtheria toxin invades the CD123 expressing tumor cells, impairing protein synthesis and triggering cell death, according to the paper.

BPDCN, which often first presents with skin manifestations, is a highly refractory hematologic malignancy. There is no standard treatment for the cancer. Doctors treat many patients still today with acute lymphocytic leukemia/lymphoma or acute myeloid leukemia-type chemotherapy. BPDCN patients treated with these chemotherapies have an overall survival of slightly more than 18 months, although many achieve complete remission at first.

“Relapse is common, quick, and often lethal,” the authors write.

Researchers have reported on small groups of BPDCN patients when went on to receive autologous and allogeneic hematopoietic stem cell transplantations, which appear to improve overall survival for some. But the studies are small and many patients are ineligible for this treatment type because they’re elderly or too frail.

There has been a great need for new BPDCN treatments that offer better efficacy and have more favorable toxicity profiles. Tagraxofusp is the first to offer these patients hope.

Administered intravenously, tagraxofusp has been evaluated for safety and efficacy in two clinical trials. In one trial published last year in the New England Journal of Medicine, researchers found overall survival among treatment naïve patients at 24 months was 52%.2 And in previously treated patients, median overall survival was 8.5 months.

“It is of note that the benefit of tagraxofusp seems persistent in patients over 70 years old, with overall response and [complete response] rates of 100% and 70%, respectively in treatment-naïve patients, and 70% and 10% respectively in previously treated patients,” according to the paper in OncoTargets and Therapy.1

But like so many types of cancer therapies, tagraxofusp comes with safety concerns. More than 70% and as many as 81% of patients in the prospective clinical trials experienced grade 3 or higher toxicities.

Capillary leak syndrome is the drug’s main toxic effect. More common toxicities include an increase in transaminases and thrombocytopenia, according to the authors.

“Acute adverse events can occur during treatment or within a few hours after the infusion. They include chills, fever, nausea, and sometimes even hypoxemia and hypotension,” they write.

Questions remain about tagraxofusp’s efficacy and how to improve patient outcomes. A good response from the drug and prognostic factors for achieving that response have yet to be defined, the authors wrote.

Researchers are already studying how combining tagraxofusp with other cytotoxic drugs or targeted therapies might improve treatment outcomes.

Providers need a good biology-driven rationale for prescribing tagraxofusp for BPDCN, as the drug is expensive and there is a lack of cost-effectiveness studies doing in real-world patients, the authors conclude.

None reported.


  • Beziat G, Ysebaert L. Tagraxofusp for the Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN): A Brief Report on Emerging Data. Onco Targets Ther. 2020;13:5199-5205.
  • Pemmaraju N, Lane AA, Sweet KL, et al. Tagraxofusp in Blastic Plasmacytoid Dendritic-Cell Neoplasm. N Engl J Med. 2019;380(17):1628-1637.
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