General Information

Elzonris (tagraxofusp-erzs) is a CD123-directed cytotoxin.

Elzonris is specifically indicated for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and in pediatric patients 2 years and older. 

Elzonris is supplied as an injection for intravenous administration. The recommended dose of Elzonris is 12 mcg/kg intravenously over 15 minutes once daily on days 1 to 5 of a 21-day cycle. The dosing period may be extended for dose delays up to day 10 of the cycle. Continue treatment until disease progression or unacceptable toxicity.

• Prior to the first dose of the first cycle, ensure serum albumin is greater than or equal to 3.2 g/dL before administering Elzonris.
• Premedicate patients with an H1-histamine antagonist (e.g., diphenhydramine hydrochloride), H2-histamine antagonist (e.g., ranitidine), corticosteroid (e.g., 50 mg intravenous methylprednisolone or equivalent) and acetaminophen (or paracetamol) approximately 60 minutes prior to each Elzonris infusion.
• Administer Cycle 1 of Elzonris in the inpatient setting with patient observation through at least 24 hours after the last infusion. Administer subsequent cycles of Elzonris in the inpatient setting or in a suitable outpatient ambulatory care setting that is equipped with appropriate monitoring for patients with hematopoietic malignancies undergoing treatment. Observe patients for a minimum of 4 hours following each infusion. 

Mechanism of Action

Elzonris (tagraxofusp-erzs) is a CD123-directed cytotoxin composed of recombinant human interleukin-3 (IL-3) and truncated diphtheria toxin (DT) fusion protein that inhibits protein synthesis and causes cell death in CD123-expressing cells.

Side Effects

Adverse events associated with the use of Elzonris may include, but are not limited to, the following:

• capillary leak syndrome
• nausea
• fatigue
• peripheral edema
• pyrexia
• weight increase
• decreases in albumin, platelets, hemoglobin,calcium and sodium
• increases in glucose, ALT and AST

The Elzonris drug label comes with the following Black Box Warning: Capillary Leak Syndrome (CLS), which may be life threatening or fatal if not properly managed, can occur in patients receiving Elzonris.

Clinical Trial Results

The FDA approval of Elzonris was based on a multicenter, multi-cohort, open-label, single-arm, clinical trial (STML-401-0114) which enrolled 47 patients with BPDCN, including 32 treatment-naïve and 15 previously-treated patients, at seven sites in the U.S. Patients received Elzonris intravenously on days 1-5 of a 21-day cycle for multiple consecutive cycles. The trial consisted of three stages: Stage 1 (lead-in, dose escalation), Stage 2 (expansion) and Stage 3 (pivotal, confirmatory). Patients were also enrolled in an additional cohort (Stage 4) to enable uninterrupted access to Elzonris. In the Stage 3 (pivotal) cohort, 13 patients with treatment-naïve BPDCN received Elzonris at the labeled dose and schedule. Efficacy was based on the rate of complete response or clinical complete response (CR/CRc), with CRc defined as complete response with residual skin abnormality not indicative of active disease. In this pivotal cohort, the CR/CRc rate was 53.8% (7/13). The median duration of CR/CRc was not reached (range: 3.9 to 12.2 months). In addition, in 29 treatment-naïve patients who received Elzonris at 12 mcg/kg/day, the overall response rate (ORR) was 90% (26/29). In these patients, the CR/CRc rate was 72% (21/29) with a median duration of CR/CRc not reached (range: 1.3 to 32.2 months). Forty-five percent (13/29) of these patients were bridged to stem cell transplant (SCT), following remission on Elzonris. The median overall survival (OS), among 29 treatment-naïve patients who received Elzonris at 12 mcg/kg/day was not reached (range: 0.2 to 42.0 months, with median follow-up of 23.0 months [range: 0.2 to 41+ months]).