Mosunetuzumab-axgb: Difference between revisions

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Created page with "{{DrugProjectFormSinglePage |authorTag={{AAP}} |genericName=mosunetuzumab-axgb |aOrAn=a |drugClass=humanized monoclonal antibody |indicationType=treatment |indication=relapsing or refractory follicular lymphoma in adults after 2 or more lines of systemic therapy. |hasBlackBoxWarning=Yes |adverseReactions=cytokine release syndrome, fatigue, rash, pyrexia, and headache. |blackBoxWarningTitle=Cytokine Release Syndrome (CRS) |blackBoxWarningBody=Cytok..."
 
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|contraindications=none
|contraindications=none
|warnings=*Cytokine Release Syndrome
|warnings=*Cytokine Release Syndrome
Clinical signs and symptoms of CRS included fever, chills, hypotension, tachycardia, and hypoxia. Concurrent neurologic adverse reactions occurred in 6% of patients and included headache, confusional state, and anxiety.


Start the therapy with a step-up dosing schedule to reduce the risk of CRS. Always provide pretreatment with corticosteroids, antihistamines and antipyretic before LUNSUMIO therapy and ensure adequate hydration with monitoring during the treatment.
At the first sign of CRS, the patient should be immediately evaluated for hospitalization and the drug should be withheld or discontinued. Patients are also advised to refrain from driving or operating heavy operating machines due to the possibility of impaired consciousness.


*neurological toxicity
*neurological toxicity
the most common presentations were headache, peripheral neuropathies, dizziness, and sometimes altered mental status like disturbance in attention, cognitive disorder, delirium, encephalopathy, and somnolence.


Patients who experience tremors, dizziness, insomnia, or other adverse reactions that impair consciousness should undergo potential neurological evaluation and refrain from driving or operating on heavy machines.


*infection
*infection
Monitor patients for signs and symptoms of infection prior to and during treatment with LUNSUMIO. LUNSUMIO should not be administered in the presence of active infection.


Caution should be exercised when considering the use of LUNSUMIO in patients with a history of recurring or chronic infections (e.g., chronic, active [[Epstein-Barr Virus]]), with underlying conditions that may predispose to infections or who have had significant prior immunosuppressive treatment.


*cytopenias
*[[cytopenias]]
 
LUNSUMIO can cause anemia, thrombocytopenia, or leukopenia. Regularly monitor the patient while they are on LUNSUMIO. Discontinue LUNSUMIO if there is significant [[cytopenia]] and consider initiating [[granulocyte colony-stimulating factor]] as applicable.


*tumor flare
*tumor flare
Some patients may experience manifestations such as new or worsening [[pleural effusions]], localized pain and swelling at the sites of [[lymphoma]] lesions, and tumor inflammation.


Close monitoring should be provided during the initial phase of the treatment for patients who have bulky tumors or disease located near their vital organs like the trachea, or spleen since the tumor can flare up and cause secondary complications due to obstruction or compression.


*embryo-fetal toxicity
*embryo-fetal toxicity
LUNSUMIO can cause fetal toxicity if given to a pregnant woman. Therefore, all the females of the reproductive age group are advised to be effective contraceptives during the treatment phase with LUNSUMIO and continue the contraception for 3 months until the last dose.
|clinicalTrials=Clinical Trials Experience
In an open-label, multicenter, multi-cohort study consisting of 218 patients with hematological malignancy, patients received step-up doses of 1 mg on Cycle 1 Day 1 and 2 mg on Cycle 1 Day 8, followed by 60 mg on Cycle 1 Day 15, and 60 mg on Cycle 2 Day 1, then 30 mg every 3 weeks in subsequent cycles. Among 218 patients who received LUNSUMIO in the treatment cycle which was for 21 days, 52% were exposed for at least 8 cycles and 8% were exposed for 17 cycles.
In this pooled population, the most common (≥ 20%) adverse reactions were cytokine release syndrome (39%), fatigue (36%), rash (34%), pyrexia (24%), and headache (21%).
The most common laboratory abnormalities (≥ 10%) were decreased lymphocyte count (92%), decreased phosphate (41%), increased glucose (40%), decreased neutrophil count (38%), increased uric acid (15%), decreased white blood cell count (22%), and decreased hemoglobin (19%).
|drugInteractions=*LUNSUMIO interacts with drugs, which are metabolized by CYP450 enzyme.
*Since LUNSUMIO releases cytokines that suppress the CYP450 enzyme leading to increased exposure of CYP450 substrates.
*Monitor for toxicity or concentrations of drugs that are CYP450 substrates where minimal concentration changes may lead to serious adverse reactions.
|FDAPregCat=X
|useInPregnancyFDA=LUNSUMIO can cause fetal harm if administered to pregnant women due to its mechanism of action. Since Human immunoglobulin IgG can cross the placenta , this Mosunetuzumab-axgb can reach the fetal blood and target the CD-20 of fetal B-cells. Mosunetuzumab-axgb can also cause T-cell activation and cytokine release leading to immune activation which may compromise pregnancy maintenance. Therefore, all the pregnant women should be advised of the potential risk to their fetus.
|useInLaborDelivery=Verify pregnancy status in females of reproductive potential prior to initiating LUNSUMIO.
|useInNursing=There is no information regarding the presence of mosunetuzumab-axgb in human milk, the effect on the breastfed child, or milk production.
However, there is a potential for fetal absorption of mosunetuzumab-axgb from breast milk since Human IgG is present in human milk. As a result, women are counseled to avoid breastfeeding during the treatment phase of LUNSUMIO and for 3 months after the last dose.
|useInPed=The safety and efficacy of LUNSUMIO have not been established in pediatric patients.
|useInGeri=Among the studies, there is an insufficient number of patients 65 years of age or older and 75 years of age or older to assess whether there are differences in safety or effectiveness in patients 65 years of age and older.
|useInGender=females of reproductive age group are advised use effective contraception during treatment with LUNSUMIO and for 3 months after the last dose.
|useInReproPotential=females of reproductive age group are advised use effective contraception during treatment with LUNSUMIO and for 3 months after the last dose.
|useInImmunocomp=LUNSUMIO can cause an adverse effect of significant cytopenia increasing the risk of infection. Therefore, LUNSUMIO is contraindicated in patients who are immunocompromised or currently on immunosuppressive drugs.
Patients on LANSUMIO should be closely monitored for laboratory abnormalities and should be started on granulocyte colony-stimulating factor if applicable.
|administration=*Only via IV infusion.
*Do not use an in-line filter to administer LUNSUMIO.
*LUNSUMIO is available in a Single-Dose Vial - 30 mg/30 mL (1 mg/mL).
*Withdraw the required volume of LUNSUMIO from the vial using a sterile needle and syringe and dilute into the infusion bag of 0.9% Sodium Chloride Injection, USP or 0.45% Sodium Chloride Injection.
**1mg dose of LUNSUMIO in 50ml or 100ml infusion bag
**2mg dose of LUNSUMIO in 50ml or 100ml infusion bag
**60mg dose of LUNSUMIO in 100ml or 250ml infusion bag
**30mg dose of LUNSUMIO in 50ml or 100ml or 250ml infusion bag
*Immediately use diluted LUNSUMIO infusion solution. If not used immediately, the diluted solution can be stored refrigerated at 2°C to 8°C (36°F to 46°F) for up to 24 hours.
|IVCompat=*Only via IV infusion.
*Do not use an in-line filter to administer LUNSUMIO.
|mechAction=Mosunetuzumab-axgb is a 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.
In Vitro Mosunetuzumab causes the release of pro-inflammatory cytokines from activated T-cells and induced lysis of B-cells.
|structure=LUNSUMIO is a humanized monoclonal anti-CD20xCD3 T-cell-dependent bispecific antibody of the immunoglobulin G1 (IgG1) isotype. Mosunetuzumab-axgb is produced in Chinese Hamster Ovary (CHO) cells by recombinant DNA technology. The approximate molecular weight is 146 kDa.
|PD=Peripheral B-cell counts decreased to undetectable levels of < 5 cells/microliter in most patients (92%) by Cycle 2 Day 1 of LUNSUMIO and the depletion was sustained at later cycles including at Cycle 4 and Cycle 8.
A spike in cytokines was also observed within 24 hours of administrating LUNSUMIO.This elevated cytokine levels generally returned to baseline before the next infusion on Cycle 1 Day 8 and on Cycle 2 Day 1. Limited data is available in subsequent treatment cycles.
|nonClinToxic=No carcinogenicity or genotoxicity studies have been conducted with mosunetuzumab-axgb.
No dedicated studies have been conducted to evaluate the effects of mosunetuzumab-axgb on fertility.
|howSupplied=Single-Dose Vial.
30 mg/30 mL
(1 mg/mL)
|storage=Store refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light.
Do not freeze. Do not shake.
|packLabel=https://dailymed.nlm.nih.gov/dailymed/image.cfm?name=lunsumio-02.jpg&setid=2ef0cf38-101c-4681-98fe-c05dc9ead443
|brandNames=LUNSUMIO
}}
}}

Latest revision as of 22:27, 13 February 2024

Mosunetuzumab-axgb
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alen Antony Pathil, M.D.[2]

Disclaimer

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Black Box Warning

Cytokine Release Syndrome (CRS)
See full prescribing information for complete Boxed Warning.
Cytokine Release Syndrome (CRS), including serious or life-threatening reactions, can occur in patients receiving LUNSUMIO. Clinical signs and symptoms of CRS includes fever, chills, hypotension, tachycardia, hypoxia, and headache along with neurologic adverse reactions such as confusional state, and anxiety. Initiate treatment with the LUNSUMIO step-up dosing schedule to reduce the risk of CRS. Withhold LUNSUMIO until CRS resolves or permanently discontinue based on severity. Patients who experience CRS should be evaluated and advised not to drive and refrain from operating heavy machinery.

Overview

Mosunetuzumab-axgb is a humanized monoclonal antibody that is FDA approved for the treatment of relapsing or refractory follicular lymphoma in adults after 2 or more lines of systemic therapy.. There is a Black Box Warning for this drug as shown here. Common adverse reactions include cytokine release syndrome, fatigue, rash, pyrexia, and headache..

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Treatment of relapsing or refractory follicular lymphoma

  • dosing information
    • always administered via intravenous infusion-1 mg/mL solution in a single-dose vial.
    • administer for 8 cycles, unless the patient experiences drug toxcity or unacceptable disease progression. Recommended dosage are:
      • Cycle 1 Day 1 – 1 mg
      • Cycle 1 Day 8 – 2 mg
      • Cycle 1 Day 15 – 60 mg
      • Cycle 2 Day 1 – 60 mg
      • Cycle 3+ Day 1 – 30 mg
    • always premedicate with antihistamines, corticosteroids, and antipyretics prior to cycle 1 and cycle 2 to reduce the risk of CRS.
    • always administer LANSUMIO to well hydrated patients.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

has no off-label use


Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

The safety and efficacy of LUNSUMIO have not been established in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

has no off label use


Contraindications

none

Warnings

Cytokine Release Syndrome (CRS)
See full prescribing information for complete Boxed Warning.
Cytokine Release Syndrome (CRS), including serious or life-threatening reactions, can occur in patients receiving LUNSUMIO. Clinical signs and symptoms of CRS includes fever, chills, hypotension, tachycardia, hypoxia, and headache along with neurologic adverse reactions such as confusional state, and anxiety. Initiate treatment with the LUNSUMIO step-up dosing schedule to reduce the risk of CRS. Withhold LUNSUMIO until CRS resolves or permanently discontinue based on severity. Patients who experience CRS should be evaluated and advised not to drive and refrain from operating heavy machinery.
  • Cytokine Release Syndrome

Clinical signs and symptoms of CRS included fever, chills, hypotension, tachycardia, and hypoxia. Concurrent neurologic adverse reactions occurred in 6% of patients and included headache, confusional state, and anxiety.

Start the therapy with a step-up dosing schedule to reduce the risk of CRS. Always provide pretreatment with corticosteroids, antihistamines and antipyretic before LUNSUMIO therapy and ensure adequate hydration with monitoring during the treatment. At the first sign of CRS, the patient should be immediately evaluated for hospitalization and the drug should be withheld or discontinued. Patients are also advised to refrain from driving or operating heavy operating machines due to the possibility of impaired consciousness.

  • neurological toxicity

the most common presentations were headache, peripheral neuropathies, dizziness, and sometimes altered mental status like disturbance in attention, cognitive disorder, delirium, encephalopathy, and somnolence.

Patients who experience tremors, dizziness, insomnia, or other adverse reactions that impair consciousness should undergo potential neurological evaluation and refrain from driving or operating on heavy machines.

  • infection

Monitor patients for signs and symptoms of infection prior to and during treatment with LUNSUMIO. LUNSUMIO should not be administered in the presence of active infection.

Caution should be exercised when considering the use of LUNSUMIO in patients with a history of recurring or chronic infections (e.g., chronic, active Epstein-Barr Virus), with underlying conditions that may predispose to infections or who have had significant prior immunosuppressive treatment.

LUNSUMIO can cause anemia, thrombocytopenia, or leukopenia. Regularly monitor the patient while they are on LUNSUMIO. Discontinue LUNSUMIO if there is significant cytopenia and consider initiating granulocyte colony-stimulating factor as applicable.

  • tumor flare

Some patients may experience manifestations such as new or worsening pleural effusions, localized pain and swelling at the sites of lymphoma lesions, and tumor inflammation.

Close monitoring should be provided during the initial phase of the treatment for patients who have bulky tumors or disease located near their vital organs like the trachea, or spleen since the tumor can flare up and cause secondary complications due to obstruction or compression.

  • embryo-fetal toxicity

LUNSUMIO can cause fetal toxicity if given to a pregnant woman. Therefore, all the females of the reproductive age group are advised to be effective contraceptives during the treatment phase with LUNSUMIO and continue the contraception for 3 months until the last dose.

Adverse Reactions

Clinical Trials Experience

Clinical Trials Experience

In an open-label, multicenter, multi-cohort study consisting of 218 patients with hematological malignancy, patients received step-up doses of 1 mg on Cycle 1 Day 1 and 2 mg on Cycle 1 Day 8, followed by 60 mg on Cycle 1 Day 15, and 60 mg on Cycle 2 Day 1, then 30 mg every 3 weeks in subsequent cycles. Among 218 patients who received LUNSUMIO in the treatment cycle which was for 21 days, 52% were exposed for at least 8 cycles and 8% were exposed for 17 cycles.

In this pooled population, the most common (≥ 20%) adverse reactions were cytokine release syndrome (39%), fatigue (36%), rash (34%), pyrexia (24%), and headache (21%). The most common laboratory abnormalities (≥ 10%) were decreased lymphocyte count (92%), decreased phosphate (41%), increased glucose (40%), decreased neutrophil count (38%), increased uric acid (15%), decreased white blood cell count (22%), and decreased hemoglobin (19%).

Postmarketing Experience

There is limited information regarding Mosunetuzumab-axgb Postmarketing Experience in the drug label.

Drug Interactions

  • LUNSUMIO interacts with drugs, which are metabolized by CYP450 enzyme.
  • Since LUNSUMIO releases cytokines that suppress the CYP450 enzyme leading to increased exposure of CYP450 substrates.
  • Monitor for toxicity or concentrations of drugs that are CYP450 substrates where minimal concentration changes may lead to serious adverse reactions.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): X LUNSUMIO can cause fetal harm if administered to pregnant women due to its mechanism of action. Since Human immunoglobulin IgG can cross the placenta , this Mosunetuzumab-axgb can reach the fetal blood and target the CD-20 of fetal B-cells. Mosunetuzumab-axgb can also cause T-cell activation and cytokine release leading to immune activation which may compromise pregnancy maintenance. Therefore, all the pregnant women should be advised of the potential risk to their fetus.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Mosunetuzumab-axgb in women who are pregnant.

Labor and Delivery

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

Nursing Mothers

There is no information regarding the presence of mosunetuzumab-axgb in human milk, the effect on the breastfed child, or milk production. However, there is a potential for fetal absorption of mosunetuzumab-axgb from breast milk since Human IgG is present in human milk. As a result, women are counseled to avoid breastfeeding during the treatment phase of LUNSUMIO and for 3 months after the last dose.

Pediatric Use

The safety and efficacy of LUNSUMIO have not been established in pediatric patients.

Geriatic Use

Among the studies, there is an insufficient number of patients 65 years of age or older and 75 years of age or older to assess whether there are differences in safety or effectiveness in patients 65 years of age and older.

Gender

females of reproductive age group are advised use effective contraception during treatment with LUNSUMIO and for 3 months after the last dose.

Race

There is no FDA guidance on the use of Mosunetuzumab-axgb with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Mosunetuzumab-axgb in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Mosunetuzumab-axgb in patients with hepatic impairment.

Females of Reproductive Potential and Males

females of reproductive age group are advised use effective contraception during treatment with LUNSUMIO and for 3 months after the last dose.

Immunocompromised Patients

LUNSUMIO can cause an adverse effect of significant cytopenia increasing the risk of infection. Therefore, LUNSUMIO is contraindicated in patients who are immunocompromised or currently on immunosuppressive drugs. Patients on LANSUMIO should be closely monitored for laboratory abnormalities and should be started on granulocyte colony-stimulating factor if applicable.

Administration and Monitoring

Administration

  • Only via IV infusion.
  • Do not use an in-line filter to administer LUNSUMIO.
  • LUNSUMIO is available in a Single-Dose Vial - 30 mg/30 mL (1 mg/mL).
  • Withdraw the required volume of LUNSUMIO from the vial using a sterile needle and syringe and dilute into the infusion bag of 0.9% Sodium Chloride Injection, USP or 0.45% Sodium Chloride Injection.
    • 1mg dose of LUNSUMIO in 50ml or 100ml infusion bag
    • 2mg dose of LUNSUMIO in 50ml or 100ml infusion bag
    • 60mg dose of LUNSUMIO in 100ml or 250ml infusion bag
    • 30mg dose of LUNSUMIO in 50ml or 100ml or 250ml infusion bag
  • Immediately use diluted LUNSUMIO infusion solution. If not used immediately, the diluted solution can be stored refrigerated at 2°C to 8°C (36°F to 46°F) for up to 24 hours.

Monitoring

There is limited information regarding Mosunetuzumab-axgb Monitoring in the drug label.

IV Compatibility

  • Only via IV infusion.
  • Do not use an in-line filter to administer LUNSUMIO.

Overdosage

There is limited information regarding Mosunetuzumab-axgb overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Mosunetuzumab-axgb Pharmacology in the drug label.

Mechanism of Action

Mosunetuzumab-axgb is a 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. In Vitro Mosunetuzumab causes the release of pro-inflammatory cytokines from activated T-cells and induced lysis of B-cells.

Structure

LUNSUMIO is a humanized monoclonal anti-CD20xCD3 T-cell-dependent bispecific antibody of the immunoglobulin G1 (IgG1) isotype. Mosunetuzumab-axgb is produced in Chinese Hamster Ovary (CHO) cells by recombinant DNA technology. The approximate molecular weight is 146 kDa.

Pharmacodynamics

Peripheral B-cell counts decreased to undetectable levels of < 5 cells/microliter in most patients (92%) by Cycle 2 Day 1 of LUNSUMIO and the depletion was sustained at later cycles including at Cycle 4 and Cycle 8.

A spike in cytokines was also observed within 24 hours of administrating LUNSUMIO.This elevated cytokine levels generally returned to baseline before the next infusion on Cycle 1 Day 8 and on Cycle 2 Day 1. Limited data is available in subsequent treatment cycles.

Pharmacokinetics

There is limited information regarding Mosunetuzumab-axgb Pharmacokinetics in the drug label.

Nonclinical Toxicology

No carcinogenicity or genotoxicity studies have been conducted with mosunetuzumab-axgb.

No dedicated studies have been conducted to evaluate the effects of mosunetuzumab-axgb on fertility.

Clinical Studies

There is limited information regarding Mosunetuzumab-axgb Clinical Studies in the drug label.

How Supplied

Single-Dose Vial. 30 mg/30 mL (1 mg/mL)

Storage

Store refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light.

Do not freeze. Do not shake.

Images

Drug Images

{{#ask: Page Name::Mosunetuzumab-axgb |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}

Package and Label Display Panel

https://dailymed.nlm.nih.gov/dailymed/image.cfm?name=lunsumio-02.jpg&setid=2ef0cf38-101c-4681-98fe-c05dc9ead443 {{#ask: Label Page::Mosunetuzumab-axgb |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}

Patient Counseling Information

There is limited information regarding Mosunetuzumab-axgb Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Mosunetuzumab-axgb interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.

Brand Names

LUNSUMIO

Look-Alike Drug Names

There is limited information regarding Mosunetuzumab-axgb Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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