Elzonris Drug Information
Generic name: TAGRAXOFUSP
CD123 Interaction [EPC] Cytotoxin [EPC]
Uses of Elzonris
ELZONRIS is indicated for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and in pediatric patients 2 years and older.
Dosage & Administration of Elzonris
Dosage Modifications
Monitor vital signs and check albumin, transaminases, and creatinine prior to preparing each dose of ELZONRIS. See Table 1 for recommended dose modifications and Table 2 for CLS management guidelines. Table 1.
Recommended ELZONRIS
Preparation for Administration Assure the following components required for dose preparation and administration are available prior to thawing ELZONRIS: One infusion syringe pump One empty 10 mL sterile vial 0.9% Sodium Chloride Injection, USP Three 10 mL sterile syringes One 1 mL sterile syringe One mini-bifuse Y-connector Microbore tubing One 0.2 micron polyethersulfone in-line filter Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Thawed ELZONRIS appearance should be a clear, colorless liquid that may contain a few white to translucent particles. Prior to dose preparation thaw at room temperature, between 15°C and 25°C (59°F and 77°F), for 15 to 30 minutes in original carton, and verify thaw visually.
Thawed vials may be held at room temperature for approximately 1 hour prior to dosage preparation. Do not force thaw. Do not refreeze vial once thawed.
Use aseptic technique for preparation of the ELZONRIS dose. Gently invert the vial at least 3 times to mix the contents. Do not shake vigorously. - Following dilution the final concentration of ELZONRIS is 100 mcg/mL. - Step 2 – Prepare the ELZONRIS infusion set. - Calculate the required volume of diluted ELZONRIS (100 mcg/mL) according to patient’s weight. - Draw up the required volume into a new syringe (if more than 10 mL of diluted ELZONRIS (100 mcg/mL) is required for the calculated patient dose, repeat step 1 with a second vial of ELZONRIS).
Label the ELZONRIS syringe. - Prepare a separate syringe with at least 3 mL of 0.9% Sodium Chloride Injection, USP to be used to flush the administration set once the ELZONRIS dose is delivered. - Label the 0.9% Sodium Chloride Injection, USP flush syringe. - Connect the 0.9% Sodium Chloride Injection, USP flush syringe to one arm of the Y-connector and ensure the clamp is closed. - Connect the product syringe to the other arm of the Y-connector and ensure the clamp is closed. - Connect the terminal end of the Y-connector to the microbore tubing. - Remove the cap from the supply side of the 0.2 micron filter and attach it to the terminal end of the microbore tubing. - Unclamp the arm of the Y-connector connected to the 0.9% Sodium Chloride Injection, USP flush syringe. Prime the Y-connector up to the intersection (do not prime the full infusion set with 0.9% Sodium Chloride Injection, USP). Re-clamp the Y-connector line on the 0.9% Sodium Chloride Injection, USP flush arm. - Remove the cap on the terminal end of the 0.2 micron filter and set it aside.
Unclamp the arm of the Y-connector connected to the product syringe, and prime the entire infusion set, including the filter. Recap the filter, and re-clamp the Y-connector line on the product side. The infusion set is now ready for delivery for dose administration.
Administer ELZONRIS within 4 hours. During this 4-hour window, the prepared dose should remain at room temperature. Do not reuse excess ELZONRIS.
Any excess material should be thrown away immediately following infusion.
Administration
Establish venous access and maintain with sterile 0.9% Sodium Chloride Injection, USP. Administer the prepared ELZONRIS dose via infusion syringe pump over 15 minutes. The total infusion time will be controlled using a syringe pump to deliver the entire dose and the 0.9% Sodium Chloride Injection, USP flush over 15 minutes.
Insert the ELZONRIS syringe into the syringe pump, open the clamp on the ELZONRIS side of the Y-connector and deliver the prepared ELZONRIS dose. Once the ELZONRIS syringe has been emptied, remove it from the pump and place the 0.9% Sodium Chloride Injection, USP flush syringe in the syringe pump. Open the clamp on the 0.9% Sodium Chloride Injection, USP flush side of the Y-connector and resume infusion via the syringe pump at the pre-specified flow to push remaining ELZONRIS dose out of the infusion line to complete delivery.
| Parameter | Severity Criteria | Dosage Modification |
|---|---|---|
| Serum albumin | Serum albumin < 3.5 g/dL or reduced ≥ 0.5 g/dL from value measured prior to initiation of the current cycle | See CLS Management Guidelines ( Table 2 ) |
| Body weight | Body weight increase ≥ 1.5 kg over pretreatment weight on prior treatment day | See CLS Management Guidelines ( Table 2 ) |
| Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) | ALT or AST increase > 5 times the upper limit of normal | Withhold ELZONRIS until transaminase elevations are ≤ 2.5 times the upper limit of normal. |
| Serum creatinine | Serum creatinine > 1.8 mg/dL (159 micromol/L) or creatinine clearance < 60 mL/minute | Withhold ELZONRIS until serum creatinine resolves to ≤ 1.8 mg/dL (159 micromol/L) or creatinine clearance ≥ 60 mL/minute. |
| Systolic blood pressure | Systolic blood pressure ≥ 160 mmHg or ≤ 80 mmHg | Withhold ELZONRIS until systolic blood pressure is < 160 mmHg or > 80 mmHg. |
| Heart rate | Heart rate ≥ 130 bpm or ≤ 40 bpm | Withhold ELZONRIS until heart rate is < 130 bpm or > 40 bpm. |
| Body temperature | Body temperature ≥ 38°C | Withhold ELZONRIS until body temperature is < 38°C. |
| Hypersensitivity reactions | Mild or moderate | Withhold ELZONRIS until resolution of any mild or moderate hypersensitivity reaction. Resume ELZONRIS at the same infusion rate. |
| Severe or life-threatening | Discontinue ELZONRIS permanently. |
| 1 If ELZONRIS dose is held: ELZONRIS administration may resume in the same cycle if all CLS signs/symptoms have resolved and the patient did not require measures to treat hemodynamic instability ELZONRIS administration should be held for the remainder of the cycle if CLS signs/symptoms have not resolved or the patient required measures to treat hemodynamic instability (e.g., required administration of intravenous fluids and/or vasopressors to treat hypotension) (even if resolved), and ELZONRIS administration may only resume in the next cycle if all CLS signs/symptoms have resolved, and the patient is hemodynamically stable. | |||
| Time of Presentation | CLS Sign/Symptom | Recommended Action | ELZONRIS Dosing Management |
| Prior to first dose of ELZONRIS in cycle 1 | Serum albumin < 3.2 g/dL | Administer ELZONRIS when serum albumin ≥ 3.2 g/dL. | |
| During ELZONRIS dosing | Serum albumin < 3.5 g/dL | Administer 25g intravenous albumin (q12h or more frequently as practical) until serum albumin is ≥ 3.5 g/dL AND not more than 0.5 g/dL lower than the value measured prior to dosing initiation of the current cycle. | Interrupt ELZONRIS dosing until the relevant CLS sign/symptom has resolved 1. |
| Serum albumin reduced by ≥ 0.5 g/dL from the albumin value measured prior to ELZONRIS dosing initiation of the current cycle | |||
| A predose body weight that is increased by ≥ 1.5 kg over the previous day’s predose weight | Administer 25g intravenous albumin (q12h or more frequently as practical), and manage fluid status as indicated clinically (e.g., generally with intravenous fluids and vasopressors if hypotensive and with diuretics if normotensive or hypertensive), until body weight increase has resolved (i.e. the increase is no longer ≥ 1.5 kg greater than the previous day’s predose weight). | ||
| Edema, fluid overload and/or hypotension | Administer 25g intravenous albumin (q12h, or more frequently as practical) until serum albumin is ≥ 3.5 g/dL. Administer 1 mg/kg of methylprednisolone (or an equivalent) per day, until resolution of CLS sign/symptom or as indicated clinically. Aggressive management of fluid status and hypotension if present, which could include intravenous fluids and/or diuretics or other blood pressure management, until resolution of CLS sign/symptom or as clinically indicated. | ||
Side Effects of Elzonris
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Safety of ELZONRIS was assessed in a single-arm clinical trial that included 122 adults with newly diagnosed or relapsed/refractory myeloid malignancies, including 86 with BPDCN, treated with ELZONRIS 12 mcg/kg daily for 5 days of a 21-day cycle. Four (3%) patients (4/122) had fatal adverse reactions, all of which were related to capillary leak syndrome.
Overall, 8% (10/122) of patients discontinued treatment with ELZONRIS due to an adverse reaction; the most common adverse reactions resulting in treatment discontinuation were hepatic toxicities, hypoalbuminemia and CLS (2% each). Table 3 summarizes the common (≥ 10%) adverse reactions with ELZONRIS in patients with myeloid malignancies. The rate of any given adverse reaction or lab abnormality was derived from all the reported events of that type.
Table 3. Adverse Reactions in ≥ 0 Clinically relevant adverse reactions occurring in less than 10% of patients treated with ELZONRIS included tumor lysis syndrome. Table 4 summarizes the clinically important laboratory abnormalities that occurred in ≥ 10% patients with myeloid malignancies treated with ELZONRIS.
Table 4. Selected Laboratory Abnormalities in Patients Receiving 0
| 1 Capillary leak syndrome defined as any event reported as CLS during treatment with ELZONRIS or the occurrence of at least 2 of the following CLS manifestations within 7 days of each other: hypoalbuminemia (including albumin value less than 3.0 g/dL), edema (including weight increase of 5 kg or more), hypotension (including systolic blood pressure less than 90 mmHg). | ||
| N=122 | ||
| All Grades % | Grade ≥ 3 % | |
| Vascular disorders | ||
| Capillary leak syndrome 1 | 53 | 11 |
| Hypotension | 25 | 7 |
| Hypertension | 14 | 6 |
| General disorders and administration site conditions | ||
| Fatigue | 45 | 7 |
| Pyrexia | 43 | 0 |
| Peripheral edema | 39 | 1 |
| Chills | 26 | 1 |
| Gastrointestinal disorders | ||
| Nausea | 45 | 0 |
| Constipation | 24 | 0 |
| Diarrhea | 21 | 0 |
| Vomiting | 19 | 0 |
| Investigations | ||
| Weight increase | 31 | 0 |
| Nervous system disorders | ||
| Headache | 28 | 0 |
| Dizziness | 21 | 0 |
| Metabolism and nutrition disorders | ||
| Decreased appetite | 22 | 0 |
| Respiratory, thoracic and mediastinal disorders | ||
| Dyspnea | 20 | 3 |
| Epistaxis | 12 | 1 |
| Cough | 12 | 0 |
| Blood and lymphatic system disorders | ||
| Febrile neutropenia | 19 | 16 |
| Musculoskeletal and connective tissue disorders | ||
| Back pain | 19 | 2 |
| Pain in extremity | 10 | 2 |
| Cardiac disorders | ||
| Tachycardia | 17 | 0 |
| Psychiatric disorders | ||
| Insomnia | 16 | 0 |
| Anxiety | 15 | 0 |
| Skin and subcutaneous tissue disorders | ||
| Pruritus | 10 | 0 |
| Treatment-Emergent Laboratory Abnormalities | ||
| All Grades % | Grade ≥ 3 % | |
| Hematology | ||
| Platelets decrease | 68 | 49 |
| Hemoglobin decrease | 61 | 30 |
| Neutrophils decrease | 38 | 29 |
| Chemistry | ||
| Glucose increase | 89 | 21 |
| ALT increase | 79 | 26 |
| AST increase | 76 | 33 |
| Albumin decrease | 72 | 1 |
| Calcium decrease | 57 | 2 |
| Sodium decrease | 52 | 9 |
| Potassium decrease | 36 | 6 |
| Phosphate decrease | 32 | 10 |
| Creatinine increase | 26 | 0 |
| Magnesium decrease | 25 | 0 |
| Alkaline phosphatase increase | 22 | 1 |
| Potassium increase | 20 | 3 |
| Magnesium increase | 13 | 4 |
| Bilirubin increase | 11 | 0 |
| Glucose decrease | 10 | 0 |
Warnings & Cautions for Elzonris
Capillary Leak Syndrome
Capillary leak syndrome (CLS), including life-threatening and fatal cases, has been reported among patients treated with ELZONRIS. Before initiating therapy with ELZONRIS, ensure that the patient has adequate cardiac function and serum albumin is greater than or equal to 3.2 g/dL. During treatment with ELZONRIS, monitor serum albumin levels prior to the initiation of each dose of ELZONRIS and as indicated clinically thereafter, and assess patients for other signs or symptoms of CLS, including weight gain, new onset or worsening edema, including pulmonary edema, hypotension or hemodynamic instability.
Hypersensitivity Reactions ELZONRIS can cause severe hypersensitivity reactions. Manifestations of hypersensitivity reported in ≥ 5% of patients include rash, pruritus, and stomatitis. Monitor patients for hypersensitivity reactions during treatment with ELZONRIS.
Interrupt ELZONRIS infusion and provide supportive care as needed if a hypersensitivity reaction should occur.
Hepatotoxicity Treatment with ELZONRIS was associated with elevations in liver enzymes. Grade 3 ALT elevations were reported in 26% (32/122) of patients. Elevated liver enzymes occurred in the majority of patients in Cycle 1 and were reversible following dose interruption.
Monitor alanine aminotransferase (ALT) and aspartate aminotransferase (AST) prior to each infusion with ELZONRIS. Withhold ELZONRIS temporarily if the transaminases rise to greater than 5 times the upper limit of normal and resume treatment upon normalization or when resolved.
Pregnancy Safety for Elzonris
Pregnancy Risk Summary Based on its mechanism of action, ELZONRIS has the potential for adverse effects on embryo-fetal development. There are no available data on ELZONRIS use in pregnant women to inform a drug-associated risk of adverse developmental outcomes. Animal reproduction or developmental toxicity studies have not been conducted with tagraxofusp-erzs.
Advise pregnant women of the potential risk to the fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a risk of birth defect, loss, or other adverse outcomes.
In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively.
Pediatric Use of Elzonris
Pediatric Use The safety and effectiveness of ELZONRIS for treatment of BPDCN have been established in pediatric patients 2 years of age and older (no data for pediatric patients less than 2 years of age). Use of ELZONRIS in these age groups is supported by evidence from an adequate and well-controlled study of ELZONRIS in adults with BPDCN and additional safety data from three pediatric patients with BPDCN, including 1 child (2 years to < 12 years old) and 2 adolescents (12 years to < 17 years old), treated with ELZONRIS at the recommended dosage. The safety profile of ELZONRIS in the pediatric patients was similar to that seen in the adults.
Efficacy for pediatric patients is extrapolated from the results of STML-401-0114. Safety and effectiveness have not been established in pediatric patients younger than 2 years of age.
Clinical Studies of Elzonris
Relapsed or Refractory Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) STML-401-0114 (NCT02113982; Study 0114) was a multicenter, open-label, single-arm, clinical trial that included 15 patients with relapsed or refractory BPDCN. Treatment consisted of ELZONRIS 12 mcg/kg on days 1 to 5 of each 21-day cycle. Patient baseline characteristics are presented in Table 7.
Table 7. Baseline Demographics of Patients with Relapsed or Refractory BPDCN 1 In the 15 patients with relapsed/refractory BPDCN, one patient achieved a CR (duration: 111 days) and one patient achieved a CRc (duration: 424 days).
| Parameter | N=13 |
|---|---|
| Gender, N (%) | |
| Male | 11 (84.6) |
| Female | 2 (15.4) |
| Age (years), N (%) | |
| Median | 65.0 |
| Minimum, Maximum | 22, 84 |
| ECOG, N (%) | |
| 0 | 8 (61.5) |
| 1 | 5 (38.5) |
| BPDCN at Baseline, N (%) | |
| Skin | 13 (100.0) |
| Bone Marrow | 7 (53.8) |
| Peripheral Blood | 3 (23.1) |
| Lymph Nodes | 6 (46.2) |
| Viscera | 2 (15.4) |
| CRc is defined as complete response with residual skin abnormality not indicative of active disease. | |
| Parameter | N=13 |
| CR/CRc* Rate, N (%) | 7 (53.8) |
| (95% CI) | (25.1, 80.8) |
| Duration of CR/CRc (months) | |
| Median | Not reached |
| Minimum, Maximum | 3.9, 12.2 |
| Duration of follow up (months) | |
| Median | 11.5 |
| Minimum, Maximum | 0.2, 12.7 |
| Parameter | N=15 |
|---|---|
| Gender, N (%) | |
| Male | 13 (86.7) |
| Female | 2 (13.3) |
| Age (years) | |
| Median | 72 |
| Minimum, Maximum | 44, 80 |
| ECOG, N (%) | |
| 0 | 5 (33.3) |
| 1 | 10 (66.7) |
| BPDCN at Baseline, N (%) | |
| Skin | 13 (86.7) |
| Bone marrow | 9 (60.0) |
| Lymph node | 8 (53.3) |
| Visceral | 4 (26.7) |
| Peripheral blood | 1 (6.7) |
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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