Mosunetuzumab-axgb (Monograph)

Drug class: Antineoplastic Agents

Medically reviewed by Drugs.com on Apr 10, 2024. Written by ASHP.

Introduction

Antineoplastic agent; bispecific CD20-directed CD3 T-cell engager.

Uses for Mosunetuzumab-axgb

Follicular Lymphoma

Treatment of relapsed or refractory follicular lymphoma in adults who previously received ≥2 lines of systemic therapy (designated an orphan drug by FDA for this use).

Current indication approved under accelerated approval based on response rate; continued FDA approval for this indication may be contingent on verification and description of clinical benefit in a confirmatory trial.

Mosunetuzumab-axgb Dosage and Administration

General

Pretreatment Screening

• Ensure adequate hydration to reduce risk of cytokine release syndrome (CRS).

• Rule out active infection prior to initiating therapy; use caution in patients with a history of recurring/chronic infections, underlying conditions that may predispose to infections, or significant prior immunosuppressive treatment.

• Verify pregnancy status in females of reproductive potential prior to starting treatment.

Patient Monitoring

• Monitor for CRS and infusion-related reactions.

• Monitor for signs and symptoms of neurologic toxicity, including immune effector cell-associated neurotoxicity (ICANS).

• Monitor for signs and symptoms of infection.

• Monitor CBC throughout treatment for neutropenia, anemia, and/or thrombocytopenia.

• Monitor for signs and symptoms of compression or obstruction due to mass effect secondary to tumor flare, particularly in patients with bulky tumors or disease located in close proximity to airways or a vital organ.

Premedication and Prophylaxis

• Administer prophylactic antimicrobials according to current guidelines.

• Premedication to reduce risk of CRS and infusion-related reactions recommended (see Premedications under Dosage and Administration).

Administration

IV Administration

Administer via IV infusion.

Available in single-dose vials containing mosunetuzumab-axgb 1 mg/mL solution.

Dilution required prior to use.

Administration by a qualified healthcare professional required with appropriate medical support to manage severe reactions such as CRS and neurologic toxicity.

Administer through a dedicated infusion line; do not use an in-line filter. May use drip chamber filters for administration.

Dilution

Determine the dose, total volume of mosunetuzumab-axgb solution required, and the number of vials needed. Obtain infusion bag of 0.9% sodium chloride or 0.45% sodium chloride; withdraw volume of solution equal to the volume of mosunetuzumab-axgb required for the patient’s dose and discard. Only use infusion bags made of polyvinyl chloride (PVC) or polyolefin such as polyethylene and polypropylene.

Withdraw required volume of mosunetuzumab-axgb from vial and dilute into the infusion bag of 0.9% sodium chloride or 0.45% sodium chloride as noted in Table 1. Discard any unused portion.

Gently mix by slow inversion. Do not shake.

Apply peel-off label from package insert to the infusion bag.

Rate of Administration

Administer over a minimum of 4 hours during cycle 1. If infusions during cycle 1 are well-tolerated, may administer infusions in subsequent treatment cycles over 2 hours.

Premedications

Premedication recommended to prevent CRS and infusion-related reactions; specific recommendations for premedication summarized in Table 2.

Dosage

Adults

Follicular Lymphoma

IV

Recommended dosage based on treatment cycle and day (see Table 3). Usual treatment duration is 8 cycles, unless unacceptable toxicity or disease progression occurs. Administer additional 9 cycles of treatment in patients who achieve partial response or have stable disease after the first 8 cycles, unless unacceptable toxicity or disease progression occurs.

Dosage Modification for Toxicity

Patients who experience CRS, neurologic toxicity, or other adverse reactions may require dosage adjustment, dose delay, or treatment discontinuation, depending on severity. Recommendations for management of CRS, neurologic toxicity, and other adverse reactions summarized in Tables 4, 5, and 6, respectively. If restarting mosunetuzumab-axgb after a dose delay, follow dosage recommendations in Table 7.

Identify CRS based on clinical presentation. Evaluate for and treat other causes of fever, hypoxia, and hypotension. If CRS is suspected, hold mosunetuzumab-axgb until CRS resolves and manage according to recommendations in Table 4. Administer supportive therapy for CRS, including intensive care if warranted. If CRS is refractory to management, consider other causes, including hemophagocytic lymphohistiocytosis.

Premedication may mask fever; if clinical presentation is consistent with CRS, follow these management guidelines.

Refer to Table 7 for information on restarting after dose delays.

Low-flow oxygen defined as oxygen delivered at <6 L/min; high-flow oxygen defined as oxygen delivered at ≥6 L/min.

At first sign of neurologic toxicity, including ICANS, hold mosunetuzumab-axgb and consider neurology evaluation. Manage as recommended in Table 5. Rule out other causes of neurologic symptoms. Provide supportive therapy, which may include intensive care.

Refer to Table 7 for information on restarting after dose delays.

Manage adverse events other than CRS or neurologic toxicity as recommended in Table 6.

Refer to Table 7 for information on restarting after dose delays.

Table 7 provides recommendations on restarting therapy after dose delay due to toxicity.

For the Day 1, Day 8, and Day 15 doses in the next cycle, administer premedication for all patients.

Special Populations

Hepatic Impairment

No dosage recommendations at this time.

Renal Impairment

No dosage recommendations at this time.

Geriatric Patients

No dosage recommendations at this time.

Related/similar drugs

rituximab, Revlimid, Rituxan, lenalidomide, Brukinsa, interferon alfa-2b

Cautions for Mosunetuzumab-axgb

Contraindications

• None.

Warnings/Precautions

Warnings

Cytokine Release Syndrome (CRS)

Serious or life-threatening cases of CRS reported (see Boxed Warning). CRS occurs most often during first treatment cycle, but may also occur in subsequent treatment cycles.

Time from start of mosunetuzumab administration to CRS onset ranges from 0.1 hours to 16 days. Median duration of CRS is 3 days.

Signs and symptoms include, but not limited to, fever, chills, hypotension, tachycardia, hypoxia, and headache.

Initiate mosunetuzumab treatment using the recommended step-up dosing schedule to reduce risk of CRS. Administer pretreatment medications, ensure adequate hydration, and monitor patients closely following administration.

At first sign of CRS, immediately evaluate patients for hospitalization, manage per current practice guidelines, and administer supportive care. Withhold mosunetuzumab until CRS resolves or permanently discontinue depending on severity.

Advise patients experiencing CRS or other adverse events that impair consciousness to avoid driving or operating heavy or potentially dangerous machinery until resolution.

Other Warnings/Precautions

Neurologic Toxicity

Serious neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), reported.

Coadministration with other products that cause dizziness or mental status changes may increase risk.

Monitor for signs and symptoms. At first sign of neurologic toxicity, including ICANS, immediately evaluate patient, consider neurology evaluation as appropriate, and provide supportive care based on severity. Withhold or permanently discontinue treatment based on severity and follow management recommendations.

Initiate neurology evaluation for patients who experience tremors, dizziness, insomnia, severe neurotoxicity, or any other adverse reactions that impair consciousness.

Advise patients at increased risk to avoid driving and refrain from operating heavy or dangerous machinery until resolution.

Infections

Serious or fatal infections reported.

Monitor for signs and symptoms of infection prior to and during treatment.

Do not administer during active infection. Use caution in patients with a history of recurring or chronic infections (e.g., chronic, active Epstein-Barr Virus), underlying conditions that may predispose to infections, or significant prior immunosuppressive treatment.

Administer prophylactic antimicrobials according to guidelines.

Withhold or consider permanent discontinuation based on infection severity.

Cytopenias

Serious or severe cytopenias, including neutropenia, anemia, and thrombocytopenia, reported.

Monitor CBC during treatment. Based on severity of cytopenias, temporarily withhold or permanently discontinue mosunetuzumab-axgb.

Consider prophylactic granulocyte colony-stimulating factor administration as applicable.

Tumor Flare

Serious or severe tumor flare reported.

Monitor for signs and symptoms of compression or obstruction due to mass effect secondary to tumor flare, particularly in patients with bulky tumors or disease located in close proximity to airways or a vital organ. If compression or obstruction develops, institute standard treatment.

Fetal/Neonatal Morbidity and Mortality

Based on mechanism of action, may cause fetal harm when administered to a pregnant woman. No human or animal data available; however, immune activation by mosunetuzumab may compromise pregnancy maintenance, and exposure to the drug in utero may cause B-cell lymphocytopenia in infants.

Advise pregnant women of potential risk to the fetus. Verify pregnancy status in females of reproductive potential prior to initiating mosunetuzumab-axgb. Advise females of reproductive potential to use effective contraception during treatment and for 3 months after last dose.

Immunogenicity

No patients developed anti-mosunetuzumab antibodies in up to 12 months of treatment.

Specific Populations

Pregnancy

No available data in pregnant women to evaluate for drug-associated risk.

Based on mechanism of action, may cause fetal harm.

Mosunetuzumab causes T-cell activation and cytokine release; immune activation may compromise pregnancy maintenance. Based on expression of CD20 on B cells and finding of B cell depletion in non-pregnant animals, the drug may also cause B-cell lymphocytopenia in infants exposed in utero. Mosunetuzumab may be transmitted from the mother to the developing fetus.

Advise women of the potential fetal risk. Verify pregnancy status in females of reproductive potential prior to initiating the drug.

Lactation

No available data regarding presence of mosunetuzumab in human milk, effects on the breast-fed infant, or effects on milk production. Because human IgG is present in human milk, and potential exists for drug absorption leading to B-cell depletion, advise women not to breast-feed during treatment and for 3 months after last dose.

Females and Males of Reproductive Potential

Verify pregnancy status in females of reproductive potential prior to initiating mosunetuzumab.

Advise females of reproductive potential to use effective contraception during treatment and for 3 months after the last dose.

Pediatric Use

Safety and effectiveness not established.

Geriatric Use

Insufficient data in patients ≥65 years of age to assess whether there are differences in safety or effectiveness compared to younger adult patients.

Hepatic Impairment

No clinically significant differences in the pharmacokinetics of mosunetuzumab in mild hepatic impairment (total bilirubin ≤ ULN with AST >ULN OR total bilirubin >1 to 1.5 times ULN with any AST level). Pharmacokinetic effects of moderate to severe hepatic impairment (total bilirubin >1.5 times ULN with any AST) unknown.

Renal impairment

No clinically significant differences in pharmacokinetics of mosunetuzumab in mild or moderate renal impairment (Cl_cr 30–89 mL/minute). Pharmacokinetic effects of severe renal impairment (Cl_cr 15–29 mL/minute) unknown.

Common Adverse Effects

Most common adverse reactions (≥20%): CRS, fatigue, rash, pyrexia, headache.

Most common Grade 3 to 4 laboratory abnormalities (≥10%): decreased lymphocyte count, decreased phosphate, increased glucose, decreased neutrophil count, increased uric acid, decreased white blood cell count, decreased hemoglobin, decreased platelets.

Drug Interactions

No clinical drug interaction studies conducted.

Drugs Metabolized by Hepatic Microsomal Enzymes

Activity of CYP enzymes may be suppressed, resulting in increased exposure of CYP substrates. Increased exposure more likely to occur after the first dose of mosunetuzumab-axgb on Cycle 1 Day 1, up to 14 days after the second 60 mg dose on Cycle 2 Day 1, and during and after cytokine release syndrome (CRS).

Monitor for toxicity or concentrations of CYP substrates where minimal concentration changes may lead to serious adverse reactions. Consult the concomitant CYP substrate drug’s prescribing information for recommended dosage modification.

Mosunetuzumab-axgb Pharmacokinetics

Absorption

Bioavailability

Pharmacokinetics dose proportional over range of 0.2–60 mg.

Steady state achieved by Cycle 4 (63–84 days).

Special Populations

Pharmacokinetics not impacted by age (19–96 years), sex, race, and ethnicity.

Distribution

Extent

Unknown if distributed into human milk.

Elimination

Half-life

16.1 days.

Stability

Storage

Parenteral

Injection Concentrate, for IV Infusion

Unopened vials: 2–8°C in original carton to protect from light.

Diluted solution: use immediately. If not used immediately, may refrigerate at 2–8°C for up to 24 hours or store at ambient temperature (9–30°C) for up to 16 hours. Bring to room temperature prior to infusion.

Actions

• T-cell engaging bispecific antibody that binds to the CD3 receptor (expressed on the surface of T cells) and CD20 (expressed on the surface of lymphoma cells and some healthy B-lineage cells).

• Activates T cells, causes release of proinflammatory cytokines, and induces lysis of B cells.

• After administration of recommended mosunetuzumab-axgb dosage, peripheral B-cell counts decreased to undetectable levels in 92% of patients by Cycle 2 Day 1; sustained depletion observed at Cycle 4 and Cycle 8.

• Induces hypogammaglobulinemia in some patients.

• Transient elevations in plasma cytokine concentrations observed after administration; levels generally returned to baseline prior to next infusion.

Advice to Patients

• Advise patients to read the FDA-approved patient labeling (Medication Guide).

• Advise patients to seek immediate medical attention if they develop signs or symptoms associated with cytokine release syndrome (CRS), including fever, chills, hypotension, tachycardia, hypoxia, and headache. Advise patients to avoid driving or operating heavy or dangerous machinery if they experience symptoms that impair consciousness.

• Advise patients to immediately contact their healthcare provider if they develop signs and symptoms associated with neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), headache, peripheral neuropathy, dizziness, or mental status changes. Advise patients to avoid driving or operating heavy or dangerous machinery if they experience neurologic toxicity that impairs consciousness.

• Inform patients about signs and symptoms of infection.

• Inform patients about signs and symptoms of cytopenias, including neutropenia, febrile neutropenia, anemia, and thrombocytopenia.

• Advise patients to report any signs and symptoms of tumor flare to their healthcare provider.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

• Advise women to inform their clinician if they are or plan to become pregnant. Advise pregnant women of the potential fetal risk. Advise females of reproductive potential to use effective contraception during treatment and for 3 months after the last dose.

• Advise women to inform their clinician if they plan to breast-feed. Advise women not to breast-feed during treatment and for 3 months after the last dose.

• Advise patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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.

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