FDA Approval Summary: Tagraxofusp-erzs For Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm

Clin Cancer Res. 2020 Feb 1;26(3):532-536. doi: 10.1158/1078-0432.CCR-19-2329. Epub 2019 Sep 23.

Abstract

Tagraxofusp-erzs (Elzonris, Stemline) is a cytotoxin that targets CD123-expressing cells. On December 21, 2018, FDA approved tagraxofusp-erzs for the treatment of blastic plasmacytoid dendritic cell neoplasms (BPDCN) in adult and pediatric patients 2 years and older. Approval was based on the response rate in a single-arm trial, Study STML-401-0114; the pivotal cohort included 13 patients with treatment-naïve BPDCN who received tagraxofusp-erzs monotherapy. The complete response or clinical complete response (CR/CRc) rate in the pivotal cohort was 54% (95% CI: 25%-81%), and the median duration of CR/CRc was not reached with a median follow-up of 11.5 months (range: 0.2-12.7). In a separate exploratory cohort, a CR/CRc was achieved by 2 (13%) patients with R/R BPDCN. Safety was assessed in 94 patients with myeloid neoplasms treated with tagraxofusp-erzs at the approved dose and schedule. The major toxicity was capillary leak syndrome (CLS), which occurred in 55% of patients and was fatal in 2%. Hepatotoxicity and hypersensitivity reactions were reported in 88% and 46% of patients, respectively. Other common (≥30%) adverse reactions were nausea, fatigue, peripheral edema, pyrexia, and weight increase. A high proportion of patients (85%) developed neutralizing antidrug antibodies. Tagraxofusp-erzs is the first FDA-approved treatment for BPDCN.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Clinical Trials as Topic
  • Dendritic Cells / drug effects*
  • Dendritic Cells / metabolism
  • Dendritic Cells / pathology
  • Drug Approval*
  • Female
  • Hematologic Neoplasms / drug therapy*
  • Hematologic Neoplasms / pathology
  • Humans
  • Interleukin-3 Receptor alpha Subunit / metabolism*
  • Male
  • Middle Aged
  • Patient Safety
  • Plasmacytoma / drug therapy*
  • Plasmacytoma / pathology
  • Recombinant Fusion Proteins / administration & dosage*
  • Treatment Outcome
  • United States
  • Young Adult

Substances

  • IL3RA protein, human
  • Interleukin-3 Receptor alpha Subunit
  • Recombinant Fusion Proteins
  • tagraxofusp