Efbemalenograstim alfa: Drug information

Dosing: Adult

Chemotherapy-induced neutropenia, prevention

Chemotherapy-induced neutropenia, prevention (nonmyeloid malignancies): SUBQ: 20 mg once per chemotherapy cycle. Administer ≥24 hours after cytotoxic chemotherapy. Do not administer within the period from 14 days before to <24 hours after administration of cytotoxic chemotherapy.

Dosing: Kidney Impairment: Adult

Altered kidney function prior to treatment initiation: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Acute kidney toxicity during treatment: Glomerulonephritis (suspected): If glomerulonephritis is suspected, evaluate for cause; if likely due to efbemalenograstim alfa, consider dose reduction or treatment interruption.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Dosing: Adjustment for Toxicity: Adult

**Efbemalenograstim Alfa Recommended Dosage Modifications for Adverse Reactions**
Adverse reaction	Efbemalenograstim alfa dosage modification
Aortitis (suspected)	Discontinue efbemalenograstim alfa.
Capillary leak syndrome (CLS)	Monitor closely. Initiate standard symptomatic treatment; may require intensive care.
Hypersensitivity (serious allergic reactions)	Permanently discontinue efbemalenograstim alfa.
Leukocytosis (WBC ≥100,000/mm³)	Discontinue efbemalenograstim alfa.
Respiratory distress syndrome (ARDS)	Discontinue efbemalenograstim alfa.
Sickle cell crisis	Discontinue efbemalenograstim alfa.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.

>10%:

Gastrointestinal: Nausea (51%)

Hematologic & oncologic: Anemia (15%), thrombocytopenia (11% to 12%; severe: <1%)

Frequency not defined: Immunologic: Antibody development

Contraindications

History of serious allergic reactions to granulocyte-stimulating factors such as efbemalenograstim alfa-vuxw, eflapegrastim, pegfilgrastim, or filgrastim products, or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Aortitis: Aortitis has been reported in patients receiving recombinant human granulocyte colony–stimulating factors (rhG-CSF); aortitis may occur as early as the first week after treatment initiation. Manifestations of aortitis may include fever, abdominal pain, malaise, back pain, and increased inflammatory markers (eg, C-reactive protein, WBC). Consider aortitis in patients who develop related signs/symptoms of unknown etiology.

• Capillary leak syndrome: Capillary leak syndrome (CLS), characterized by hypotension, hypoalbuminemia, edema, and hemoconcentration, may occur in patients receiving rhG-CSF products. CLS episodes vary in frequency and severity. CLS may be life-threatening if treatment is delayed.

• Hematologic effects: Leukocytosis (WBC ≥100,000/mm³) has been reported in patients receiving rhG-CSF products. Thrombocytopenia has also been reported.

• Hypersensitivity: Serious allergic reactions (including anaphylaxis) may occur with rhG-CSF products, such as efbemalenograstim alfa.

• Myelodysplastic syndrome: Myelodysplastic syndrome and acute myeloid leukemia have been associated with rhG-CSF products when used in conjunction with chemotherapy and/or radiotherapy in patients with breast and lung cancer.

• Nephrotoxicity: Glomerulonephritis has occurred, and generally resolved after dose reduction or discontinuation of rhG-CSF products. Diagnosis was made by the presence of azotemia, microscopic and macroscopic hematuria, proteinuria, and renal biopsy.

• Respiratory distress syndrome: Acute respiratory distress syndrome (ARDS) has been reported with use of rhG-CSF products; evaluate patients with pulmonary symptoms such as fever, pulmonary infiltrates, or respiratory distress for ARDS.

• Splenic rupture: Rare cases of splenic rupture have been reported (some fatal) in patients treated with rhG-CSF products; evaluate for an enlarged spleen or splenic rupture in patients who report left upper abdominal pain or shoulder pain.

Disease-related concerns:

• Sickle cell disease: Severe and sometimes fatal sickle cell crises may occur in patients with sickle cell disorders receiving rhG-CSF products.

Dosage form specific issues:

• Latex: The packaging (needle cover) may contain latex.

Other warnings/precautions:

• Nuclear imaging: Increased bone marrow hematopoietic activity due to colony-stimulating factor use has been associated with transient-positive bone imaging changes; interpret results accordingly.

• Tumor growth factor: The G-CSF receptor through which efbemalenograstim alfa works has been located on tumor cell lines. The possibility that efbemalenograstim alfa may potentially act as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, cannot be excluded (efbemalenograstim alfa is not approved for myeloid malignancies).

Product Availability

FDA-approved November 2023; anticipated availability currently unknown.

Administration: Adult

SUBQ: Remove efbemalenograstim alfa carton from refrigerator prior to administration (retain prefilled syringe within the carton); allow to reach room temperature (for at least 30 minutes) prior to administration. Administer the entire contents of the prefilled syringe SUBQ. The syringe does not have graduation marks and is intended to deliver the entire contents (20 mg/mL) upon administration. Inject into the abdomen (avoid a 2-inch diameter around the navel), the back or side of upper arms, or the thigh; rotate administration sites. Avoid injecting into scar tissues or areas that are reddened, inflamed, or swollen. The needle safety device will be triggered upon administration of the entire contents, pulling the needle from the skin and into the syringe barrel.

Use: Labeled Indications

Chemotherapy-induced neutropenia, prevention: To decrease the incidence of infection, as manifested by febrile neutropenia, in adults with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.

Limitations of use: Efbemalenograstim alfa is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic cell transplantation.

Medication Safety Issues

Sound-alike/look-alike issues:

Efbemalenograstim alfa may be confused with eflapegrastim, filgrastim, lenograstim, lipefilgrastim, pegfilgrastim, sargramostim, tbo-filgrastim.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Belotecan: Granulocyte Colony-Stimulating Factors may enhance the neutropenic effect of Belotecan. Management: Do not administer granulocyte colony-stimulating factor (G-CSF) until at least 24 hours after completion of belotecan administration. Monitor neutrophil counts and signs/symptoms of neutropenic fever in patients receiving this combination. Risk D: Consider therapy modification

Betibeglogene Autotemcel: Granulocyte Colony-Stimulating Factors may interact via an unknown mechanism with Betibeglogene Autotemcel. Management: Granulocyte-colony stimulating factor is not recommended for 21 days after betibeglogene autotemcel infusion. Risk X: Avoid combination

Bleomycin: Granulocyte Colony-Stimulating Factors may enhance the adverse/toxic effect of Bleomycin. Specifically, the risk for pulmonary toxicity may be increased. Management: Avoid use of granulocyte colony-stimulating factors 24 hours before (14 days for pegfilgrastim) and 24 hours after the last dose of bleomycin. Risk D: Consider therapy modification

Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy

Exagamglogene Autotemcel: Granulocyte Colony-Stimulating Factors may enhance the adverse/toxic effect of Exagamglogene Autotemcel. Risk X: Avoid combination

Lovotibeglogene Autotemcel: Granulocyte Colony-Stimulating Factors may enhance the adverse/toxic effect of Lovotibeglogene Autotemcel. Risk X: Avoid combination

Rozanolixizumab: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy

Tisagenlecleucel: Granulocyte Colony-Stimulating Factors may enhance the adverse/toxic effect of Tisagenlecleucel. Risk X: Avoid combination

Topotecan: Granulocyte Colony-Stimulating Factors may enhance the adverse/toxic effect of Topotecan. Specifically, the risk for the development of interstitial lung disease may be increased. Granulocyte Colony-Stimulating Factors may enhance the myelosuppressive effect of Topotecan. Management: Avoid use of granulocyte colony-stimulating factors 24 hours before (14 days for pegfilgrastim) and 24 hours after the last dose of topotecan. Additionally, monitor patients closely for the development of interstitial lung disease with this combination. Risk D: Consider therapy modification

Pregnancy Considerations

Adverse outcomes were not observed in animal reproduction studies following administration of efbemalenograstim alfa with cumulative doses up to 2.6 times the recommended human dose (based on AUC) in pregnant rats or 0.7 times the recommended human dose in pregnant rabbits.

Breastfeeding Considerations

It is not known if efbemalenograstim alfa is present in breast milk.

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, the benefits of treatment to the mother, as well as the mother's underlying condition.

Monitoring Parameters

Monitor CBC (including platelets) during therapy. Evaluate for an enlarged spleen or splenic rupture in patients who report left upper abdominal pain or shoulder pain. Evaluate for acute respiratory distress syndrome (ARDS) in patients who develop fever and lung infiltrates or respiratory distress. Monitor for signs/symptoms of aortitis (fever, abdominal pain, malaise, back pain, increased inflammatory markers), serious allergic reactions, sickle cell crisis (in patient with sickle cell disease), glomerulonephritis, and capillary leak syndrome. Monitor for signs/symptoms of myelodysplastic syndromes and acute myeloid leukemia.

Mechanism of Action

Efbemalenograstim alfa is a long-acting recombinant human granulocyte growth factor conjugated with a recombinant human IgG2-Fc fragment allowing for an extended half-life (Ref). Efbemalenograstim alfa binds to granulocyte colony-stimulating factor receptors on hematopoietic cells, triggering signaling pathways to stimulate cell differentiation, proliferation, commitment, and end cell functional activation.

Pharmacokinetics (Adult Data Unless Noted)

Onset: Median ANC peak ~24 hours after efbemalenograstim alfa administration (day 4 in patients with breast cancer receiving EC [epirubicin and cyclophosphamide] chemotherapy; day 3 in patients with breast cancer receiving TAC [docetaxel, doxorubicin, and cyclophosphamide] chemotherapy).

Distribution: Patients with breast cancer: 18.8 L (cycle 1), 40.7 L (cycle 3).

Metabolism: Into small peptides via catabolic pathways.

Half-life elimination: 35.6 hours (cycle 1), 36.9 hours (cycle 3).

Time to peak: Patients with breast cancer receiving EC chemotherapy: 24 to 48 hours (cycle 1), 9 to 30 hours (cycle 3); patients with breast cancer receiving TAC chemotherapy: 36 hours (cycle 1), 24 to 30 hours (cycle 3).

Excretion: Clearance: 0.36 L/hour (cycle 1), 0.76 L/hour (cycle 3); serum clearance of efbemalenograstim alfa is directly related to neutrophil receptor binding and number of neutrophils present.

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Efbemalenograstim alfa: Drug information