Efbemalenograstim Alfa-vuxw (Monograph)

Brand name: Ryzneuta
Drug class: Hematopoietic Agents

Introduction

Efbemalenograstim alfa-vuxw is a recombinant fusion protein consisting of human granulocyte stimulating factor (G-CSF) and the Fc portion of human IgG2.

Uses for Efbemalenograstim Alfa-vuxw

Efbemalenograstim alfa-vuxw has the following uses:

Efbemalenograstim alfa-vuxw is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in adult patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.

Efbemalenograstim alfa-vuxw is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

Efbemalenograstim Alfa-vuxw Dosage and Administration

General

Efbemalenograstim alfa-vuxw is available in the following dosage form(s) and strength(s):

Injection: 20 mg/mL solution in a single-dose prefilled syringe.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

Recommended Dose: 20 mg administered subcutaneously once per chemotherapy cycle.
Administer approximately 24 hours after cytotoxic chemotherapy. Do not administer efbemalenograstim alfa-vuxw between 14 days before and 24 hours after administration of cytotoxic chemotherapy.

Cautions for Efbemalenograstim Alfa-vuxw

Contraindications

Patients with a history of serious allergic reactions to granulocyte stimulating factors such as efbemalenograstim alfa-vuxw, pegfilgrastim, or filgrastim products.

Warnings/Precautions

Splenic Rupture

Splenic rupture, including fatal cases, can occur following the administration of recombinant human granulocyte colony-stimulating factor (rhG CSF) products, such as efbemalenograstim alfa-vuxw. Evaluate for an enlarged spleen or splenic rupture in patients who report left upper abdominal or shoulder pain after receiving efbemalenograstim alfa-vuxw.

Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) can occur in patients receiving rhG-CSF products, such as efbemalenograstim alfa-vuxw. Evaluate patients who develop fever and lung infiltrates or respiratory distress after receiving efbemalenograstim alfa-vuxw for ARDS. Discontinue efbemalenograstim alfa-vuxw in patients with ARDS.

Serious Allergic Reactions

Serious allergic reactions, including anaphylaxis, can occur in patients receiving rhG-CSF products, such as efbemalenograstim alfa-vuxw. Permanently discontinue efbemalenograstim alfa-vuxw in patients with serious allergic reactions. Efbemalenograstim alfa-vuxw is contraindicated in patients with a history of serious allergic reactions to the drug or other rhG-CSF products such as pegfilgrastim, eflapegrastim or filgrastim products.

Sickle Cell Crisis in Patients with Sickle Cell Disorders

Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disorders receiving rhG-CSF products, such as efbemalenograstim alfa-vuxw. Discontinue efbemalenograstim alfa-vuxw if sickle cell crisis occurs.

Glomerulonephritis

Glomerulonephritis has occurred in patients receiving rhG-CSF products. The diagnoses were based upon azotemia, hematuria (microscopic and macroscopic), proteinuria, and renal biopsy. Generally, events of glomerulonephritis resolved after dose-reduction or discontinuation of rhG-CSF. If glomerulonephritis is suspected, evaluate for cause. If causality is likely, consider dose-reduction or interruption of efbemalenograstim alfa-vuxw.

Leukocytosis

White blood cell (WBC) counts of 100 × 10⁹/L or greater have been observed in patients receiving rhG-CSF products. Monitor complete blood count (CBC) during efbemalenograstim alfa-vuxw therapy. Discontinue treatment if WBC count of 100 × 10⁹/L or greater occurs.

Thrombocytopenia

Thrombocytopenia has been reported in patients receiving rhG-CSF products. Thrombocytopenia occurred in 11% of efbemalenograstim alfa-vuxw-treated patients. One patient (0.4%) experienced severe thrombocytopenia. Monitor platelet counts.

Capillary Leak Syndrome

Capillary leak syndrome has been reported after administration of rhG-CSF products and is characterized by hypotension, hypoalbuminemia, edema, and hemoconcentration. Episodes vary in frequency and severity, and may be life-threatening if treatment is delayed. Patients who develop symptoms of capillary leak syndrome should be closely monitored and receive standard symptomatic treatment, which may include a need for intensive care.

Potential for Tumor Growth Stimulatory Effects on Malignant Cells

The granulocyte colony-stimulating factor (G-CSF) receptor through which efbemalenograstim alfa-vuxw acts has been found on tumor cell lines. The possibility that efbemalenograstim alfa-vuxw acts as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which the drug is not approved, cannot be excluded.

Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) in Patients with Breast and Lung Cancer

MDS and AML have been associated with the use of rhG-CSF products in conjunction with chemotherapy and/or radiotherapy in patients with breast and lung cancer. Monitor patients for signs and symptoms of MDS/AML in these settings.

Aortitis

Aortitis has been reported in patients receiving rhG-CSF products. It may occur as early as the first week after start of therapy. Manifestations may include generalized signs and symptoms such as fever, abdominal pain, malaise, back pain, and increased inflammatory markers (e.g., c-reactive protein and white blood cell count). Consider aortitis in patients who develop these signs and symptoms without known etiology. Discontinue efbemalenograstim alfa-vuxw if aortitis is suspected.

Nuclear Imaging

Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone imaging changes. This should be considered when interpreting bone imaging results.

Specific Populations

Pregnancy

Although available data with efbemalenograstim alfa-vuxw use in pregnant women are insufficient to establish whether there is a drug associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes, there are available data from published studies in pregnant women exposed to other human G-CSF products. These studies have not established an association of G-CSF product use during pregnancy with major birth defects, miscarriage, or adverse maternal or fetal outcomes.

In animal studies, no evidence of reproductive/developmental toxicity occurred in the offspring of pregnant rats and rabbits that received cumulative doses of efbemalenograstim alfa-vuxw approximately 2.6 and 0.7 times, respectively, the recommended human dose (based on body surface area).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Lactation

There are no data on the presence of efbemalenograstim alfa-vuxw or its metabolite in either human or animal milk, the effects on the breastfed child, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for efbemalenograstim alfa-vuxw and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical studies of efbemalenograstim alfa-vuxw did not include sufficient numbers of subjects 65 years of age and over to determine whether they respond differently from younger subjects. Other reported clinical experience with efbemalenograstim alfa-vuxw has not identified differences in responses between the elderly and younger patients.

Common Adverse Effects

Most common adverse reactions (≥10%) were nausea, anemia, and thrombocytopenia.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

Efbemalenograstim alfa-vuxw is a colony-stimulating factor that acts on hematopoietic cells by binding to specific cell surface receptors, thereby stimulating proliferation, differentiation, commitment, and end cell functional activation.

Advice to Patients

Advise the patient to read the FDA-approved patient labeling (Patient Information).
Rupture or enlargement of the spleen may occur. Symptoms include left upper quadrant abdominal pain or left shoulder pain. Advise patients to report pain in these areas to their healthcare provider immediately.
Dyspnea, with or without fever, progressing to acute respiratory distress syndrome, may occur. Advise patients to report dyspnea to their healthcare provider immediately.
Serious allergic reactions may occur, which may be signaled by rash, facial edema, wheezing, dyspnea, hypotension, or tachycardia. Advise patients to seek immediate medical attention if signs or symptoms of hypersensitivity reaction occur.
In patients with sickle cell disease, sickle cell crisis and death have occurred with use of human granulocyte colony-stimulating factors. Discuss potential risks and benefits for patients with sickle cell disease prior to the administration of efbemalenograstim alfa-vuxw.
Glomerulonephritis may occur. Symptoms include swelling of the face or ankles, dark colored urine or blood in the urine, or a decrease in urine production. Advise patients to report signs or symptoms of glomerulonephritis to their healthcare provider immediately.
Capillary leak syndrome may occur. Symptoms include hypotension and edema. Advise patients to report signs and symptoms of capillary leak syndrome to their healthcare provider immediately.
There may be an increased risk of myelodysplastic syndrome (MDS) and/or acute myeloid leukemia (AML) in patients with breast and lung cancer who receive efbemalenograstim alfa-vuxw in conjunction with chemotherapy and/or radiation therapy. Symptoms of MDS and AML may include tiredness, fever, and easy bruising or bleeding. Advise patients to report to their physician signs and symptoms of MDS/AML.
Aortitis may occur. Symptoms may include fever, abdominal pain, malaise, back pain, and increased inflammatory markers. Advise patients to report signs and symptoms of aortitis to their physician immediately.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.