Dosing & Uses
AdultPediatric
Dosage Forms & Strengths
injectable solution
- 1mg/mL (2.5-mL, 10-mL single-dose vials)
B-Cell Lymphoma
Indicated for relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS) or large B-cell lymphoma (LBCL) arising from follicular lymphoma, after ≥2 lines of systemic therapy
Step-up dose schedule
- Dosing begins with step-up dose schedule
- Administer premedications (ie, dexamethasone, acetaminophen, diphenhydramine) for each dose
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Cycle 1
- Day 1: Obinutuzumab 1000 mg IV x 1 dose 7 days before initiating glofitamab to deplete circulating and lymphoid tissue B cells
- Day 8 (Step-up dose 1): 2.5 mg IV over 4 hr x 1
- Day 15 (Step-up dose 2): 10 mg IV over 4 hr x 1
- If cytokine release syndrome (CRS) occurs, extend infusion rate of subsequent dose up to 8 hr
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Cycle 2
- Day 1: 30 mg IV over 4 hr
- If CRS experienced with previous dose, extend infusion rate up to 8 hr
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Cycle 3-12
- Day 1: 30 mg IV over 2 hr
- If CRS experienced with previous dose, maintain duration of infusion at 4 hr
- Continue for a maximum of 12 cycles (inclusive of Cycle 1 step-up dosing) or until disease progression or unacceptable toxicity, whichever occurs first
Dosage Modifications
Cytokine release syndrome (CRS)
- Identify CRS based on clinical presentation
- Evaluate for and treat other causes of fever, hypoxia, and hypotension
- Administer supportive care for CRS
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Grade 1
- Defined as temperature ≥100.4ºF (38ºC); premedication may mask fever
- If clinical presentation is consistent with CRS, withhold glofitamab and manage per current practice guidelines
- If symptoms resolve, restart infusion at a slower rate; may extend up to 8 hr, as appropriate for that cycle
- Ensure CRS symptoms are resolved for ≥72 hr before next dose
- Consider slower infusion rate for next dose
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Grade 2
- Defined as temperature ≥100.4ºF (38ºC) with hypotension not requiring vasopressors and/or hypoxia requiring low-flow oxygen by nasal cannula or blow-by
- Withhold glofitamab and manage per current practice guidelines
- If symptoms resolve, restart infusion at a slower rate; may extend up to 8 hr, as appropriate for that cycle
- Ensure CRS symptoms are resolved for at least 72 hr before next dose
- For next dose, consider a slower infusion rate, monitor more frequently, and consider hospitalization
- For recurrent Grade 2 CRS, manage per Grade 3 CRS
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Grade 3 (or recurrent Grade 2)
- Defined as temperature ≥100.4ºF (38ºC) with hypotension requiring vasopressor (with or without vasopressin) and/or hypoxia requiring high-flow oxygen by nasal cannula, face mask, non-rebreather mask, or Venturi mask
- Withhold glofitamab and manage per current practice guidelines, which may include intensive care
- Ensure CRS symptoms are resolved for at least 72 hr before next dose
- Hospitalize for next dose, monitor more frequently, and consider a slower infusion rate; may extend up to 8 hr, as appropriate for that cycle
- For recurrent Grade 3 CRS, permanently discontinue
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Grade 4 (or recurrent Grade 3)
- Defined as temperature ≥100.4ºF (38ºC) with hypotension requiring multiple vasopressors (excluding vasopressin) and/or hypoxia requiring oxygen by positive pressure (eg, continuous positive airway pressure [CPAP], bilevel positive airway pressure [BiPAP], intubation, and mechanical ventilation)
- Permanently discontinue and manage per current practice guidelines
Neurologic toxicity
- Management recommendations for neurologic toxicity, including immune effector cell–associated neurotoxicity syndrome (ICANS)
- At the first sign of neurologic toxicity, including ICANS, consider neurology evaluation and withholding glofitamab, based on type and severity of neurotoxicity
- Rule out other causes of neurologic symptoms
- Provide supportive therapy
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Grade 1
- Continue glofitamab and monitor neurologic toxicity symptoms
- If ICANS, manage per current practice guidelines
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Grade 2
- Withhold until neurologic toxicity symptoms improve to Grade 1 or baseline
- Consider the type of neurologic toxicity before deciding to withhold
- Evaluate benefit-risk before restarting
- Provide supportive therapy, and consider neurologic evaluation
- If ICANS, manage per current practice guidelines
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Grade 3
- Withhold until neurologic toxicity symptoms improve to Grade 1 or baseline for ≥7 days
- Evaluate benefit-risk before restarting
- For neurologic events lasting >7 days, consider permanently discontinuing
- Provide supportive therapy, and consider neurology evaluation
- If ICANS, manage per current practice guidelines
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Grade 4
- Permanently discontinue
- Provide supportive therapy, which may include intensive care, and consider neurology evaluation
- If ICANS, manage per current practice guidelines
Infections
Grades 1-4: Withhold for active infection until infection resolves
Grade 4: Consider permanent discontinuation
Tumor flare H4
Monitor for signs and symptoms of compression or obstruction due to mass effect secondary to tumor flare
Grades 2-4: Monitor for signs and symptoms of compression or obstruction due to mass effect secondary to tumor flare, and institute appropriate treatment including antihistamine and corticosteroids
Withhold glofitamab until tumor flare resolves
Hematologic toxicities
- Neutropenia (absolute neutrophil count [ANC] < 0.5 x 109/L): Withhold glofitamab until ANC ≥0.5 x 109/L
- Thrombocytopenia (platelet count <50 x 109/L) Withhold glofitamab until platelet count ≥50 x 109/L
Other adverse reactions
- Grade≥ 3: Withhold glofitamab until the toxicity resolves to Grade 1 or baseline
Renal impairment
- Mild to moderate (CrCl 30 to <90 mL/min): No dosage adjustment necessary
- Severe or end-stage renal disease (CrCl <30 mL/min): Pharmacokinetics are unknown
Hepatic impairment
- Mild (total bilirubin >ULN to ≤1.5x ULN or AST >ULN): No dosage adjustment necessary
- Moderate to severe (total bilirubin >1.5x ULN and any AST): Pharmacokinetics of glofitamab are unknown
Dosing Considerations
Before initiating
- Verify pregnancy status in females of reproductive potential
- Tumor lysis syndrome prophylaxis: Administer antihyperuricemics to patients at risk of tumor lysis syndrome, ensure adequate hydration status, and monitor as appropriate
- Antiviral prophylaxis: Consider initiating antiviral prophylaxis to prevent herpes virus reactivation; consider prophylaxis for cytomegalovirus infection in patients at increased risk
- Pneumocystis jirovecii pneumonia (PJP): Consider PJP prophylaxis
Monitoring for CRS
- Administer infusions in a healthcare setting with immediate access to medical support to manage CRS, including severe CRS
- Step-up dose 1 (2.5 mg on Cycle 1 Day 8): Hospitalize patient during and for 24 hr after completing infusion
- Patients who experienced any grade CRS: Hospitalize during and for 24 hours after completion of step-up dose 2 (10 mg on Cycle 1 Day 15), CRS with step-up dose 2 can occur in patients who did not experience CRS with step-up dose 1
- Subsequent infusions (30 mg on Day 1 of Cycle 2 or subsequent cycles), patients who experienced Grade ≥2 CRS with their previous infusion: Hospitalized during and for 24 hr after completing infusion
Safety and efficacy not established
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Adverse Effects
>10%
All grades
- Lymphocytes decreased (90%)
- Fibrinogen decreased (84%)
- Hemoglobin decreased (72%)
- Cytokine release syndrome (70%)
- Phosphate decreased (69%)
- Neutrophils decreased (56%)
- Platelets decreased (56%)
- Sodium decreased (49%)
- Calcium decreased (48%)
- Gamma-glutamyl transferase (GGT) increased (33%)
- Potassium decreased (32%)
- Uric acid increased (23%)
- Musculoskeletal pain (21%)
- Fatigue (20%)
- Rash (20%)
- Pyrexia (16%)
- Constipation (14%)
- Diarrhea (14%)
- Tumor flare (12%)
Grade 3 or 4
- Lymphocytes decreased (83%)
- Neutrophils decreased (26%)
- Fibrinogen decreased (21%)
- Phosphate decreased (28%)
- Uric acid increased (23%)
1-10%
All grades
- Edema (10%)
- Nausea (10%)
- Abdominal pain (10%)
- Headache (10%)
Grade 3 or 4
- GGT increased (9%)
- Hemoglobin decreased (8%)
- Platelets decreased (8%)
- Sodium decreased (7%)
- Potassium decreased (6%)
- Cytokine release syndrome (4.1%)
- Tumor flare (2.8%)
- Musculoskeletal pain (2.1%)
- Calcium decreased (2.1%)
- Fatigue (1.4%)
- Rash (1.4%)
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Warnings
Cytokine Release Syndrome
- Cytokine release syndrome (CRS), including serious or fatal reactions, can occur
- Premedicate before each dose and initiate treatment with step-up dosing schedule to reduce risk
- If CRS occurs, withhold glofitamab until CRS resolves or permanently discontinue, based on severity
Contraindications
None
Cautions
Serious or fatal infections reported; administer antimicrobial prophylaxis according to guidelines; do not administer to patients with an active infection; monitor patients before and during treatment for infection and treat appropriately
Based on its mechanism of action, fetal harm may occur when administered to pregnant females
Tumor flares
- May cause serious tumor flare; symptoms include localized pain and swelling at the sites of the lymphoma lesions and/or dyspnea from new pleural effusions
- Closely monitor patients with bulky tumors or disease located near airways or a vital organ during initial therapy
- Monitor for signs and symptoms of compression or obstruction due to mass effect secondary to tumor flare, and institute appropriate treatment
- Withhold therapy until tumor flare resolves
Neurologic toxicity
- May cause serious and fatal neurologic toxicity, including ICANS
- Coadministration with other products that cause dizziness or mental status changes may increase risk of neurologic toxicity
- Optimize concomitant medications and hydration to avoid dizziness or mental status changes
- Institute fall precautions as appropriate
- Monitor for signs and symptoms of neurologic toxicity, evaluate, and provide supportive therapy; withhold or permanently discontinue therapy based on severity
- Promptly evaluate patients who experience neurologic toxicity such as tremors, dizziness, or adverse reactions that may impair cognition or consciousness; consider neurology evaluation
- Advise affected patients to refrain from driving and/or engaging in hazardous occupations or activities (eg, operating heavy or potentially dangerous machinery) until neurologic toxicity fully resolves
Cytokine release syndrome
- May cause serious and fatal CRS
- Most common manifestations of CRS included fever, tachycardia, hypotension, chills, and hypoxia
- Administer glofitamab in a facility equipped to monitor and manage CRS
Drug interactions overview
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Sensitive CYP substrates
- Monitor for toxicities or drug concentrations of sensitive CYP substrates
- Glofitamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates
- Increased exposure of CYP substrates is more likely to occur after first dose of glofitamab (Cycle 1 Day 8) and up to 14 days after the first 30-mg dose (Cycle 2 Day 1) and during and after CRS
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Pregnancy & Lactation
Pregnancy
- Based on its mechanism of action, fetal harm may occur when administered to pregnant females
- No data are available on use in pregnant females to evaluate for a drug-associated risk
- No animal reproductive and developmental toxicity studies have been conducted
- Glofitamab causes T-cell activation and cytokine release; immune activation may compromise pregnancy maintenance; human immunoglobulin G (IgG) is known to cross the placenta; therefore, glofitamab has the potential to be transmitted from mother to developing fetus
- Advise women of potential risk to fetus
- Verify pregnancy status in females of reproductive potential prior to initiating
Contraception
- Females of reproductive potential: Use effective contraception during treatment and for 1 month after last dose
Lactation
There are no data on presence of glofitamab in human milk or effects on breastfed children or milk production
Advise females not to breastfeed during treatment and for 1 month after the last dose
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Previous
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Pharmacology
Mechanism of Action
Bispecific CD3-directed and CD20-directed antibody binds to CD20 expressed on the surface of B cells and to CD3 receptor expressed on the surface of T cells
Glofitamab causes T-cell activation and proliferation, secretion of cytokines, and lysis of CD20-expressing B cells
Absorption
Trough concentration
- First full 30-mg dose: 0.52 mcg/mL
- Steady-state 30-mg dose: 0.59 mcg/mL
Peak plasma concentration
- First full 30-mg dose: 9.41 mcg/mL
- Steady-state 30-mg dose: 9.44 mcg/mL
AUC
- First full 30-mg dose: 44.5 day∙mcg/mL
- Steady-state 30-mg dose: 48.6 day∙mcg/mL
Distribution
Vd: 5.9 L
Metabolism
Metabolized into small peptides by catabolic pathways
Elimination
Clearance: 0.617 L/day
Half-life: 7.6 days
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Administration
IV Incompatibilities
Do not mix with other drugs
IV Compatibilities
0.9% NaCl
0.45% NaCl
Compatible with IV infusion bags composed of polyvinyl chloride, polyethylene, polypropylene, or non-PVC polyolefin
No incompatibilities observed with infusion sets with product-contacting surfaces of polyurethane, PVC, or PE, and in-line filter membranes composed of polyethersulfone or polysulfone
IV Preparation
Visually inspect parenteral drug for particulate matter and discoloration before administering; solution should be clear and colorless; discard vial if solution is cloudy, discolored, or contains visible particles
Use aseptic technique when preparing diluted solution
Determine dose, total drug volume, and number of vials needed
Dilution
-
Withdraw and discard volume of 0.9% or 0.45% NaCl from infusion bag as follows
- 2.5-mg dose: Withdraw 27.5 mL from 50-mL infusion bag, and then add glofitamab 2.5 mg (2.5 mL)
- 10-mg dose: Withdraw 10 mL from either a 50-mL or 100-mL infusion bag, and then add glofitamab 10 mg (10 mL)
- 30-mg dose: Withdraw 30 mL from either a 50-mL or 100-mL infusion bag, and then add glofitamab 30 mg (30 mL)
- Final concentration of diluted infusion bag is 0.1-0.6 mg/mL; discard any remaining unused drug
Pretreatment
Cycle 1 Day 1
- Pretreat all patients with obinutuzumab 1,000 mg IV x 1 dose 7 days before initiating glofitamab, to deplete circulating and lymphoid tissue B cells
- Infuse obinutuzumab at 50 mg/hr; may increase infusion rate in 50 mg/hr-increments every 30 minutes up to 400 mg/hr
- Refer to obinutuzumab prescribing information for complete dosing information
Cycle 1, Day 8 and Day 15, Cycle 2 and 3
- Dexamethasone 20 mg IV completed at least 1 hr before infusion
- If dexamethasone is not available, administer prednisone 100 mg, prednisolone 100 mg, or methylprednisolone 80 mg IV
- Acetaminophen 500-1,000 mg PO at least 30 minutes before infusion
- Diphenhydramine 50 mg PO/IV or equivalent completed at least 30 minutes before infusion
Subsequent cycles
- Acetaminophen 500-1,000 mg PO at least 30 minutes before infusion
- Diphenhydramine 50 mg PO/IV or equivalent completed at least 30 minutes before infusion
-
Any grade CRS experienced with previous dose
- Dexamethasone 20 mg IV completed at least 1 hr before infusion
- If dexamethasone is not available, administer prednisone 100 mg, prednisolone 100 mg, or methylprednisolone 80 mg IV
IV Administration
Ensure adequate hydration before administering
Administer only as IV infusion through a dedicated infusion line that includes a sterile 0.2-micron inline filter
Restarting after dose delay
-
Last dose: Obinutuzumab pretreatment (Cycle 1 Day 1)
- ≤2 weeks: Administer glofitamab 2.5 mg (Cycle 1 Day 8), then resume planned treatment schedule
- >2 weeks: Repeat obinutuzumab 1,000 mg pretreatment (Cycle 1 Day 1);
- then administer glofitamab 2.5 mg (Cycle 1 Day 8) and resume planned treatment schedule
- Hospitalize patient during and for 24 hr after completing infusion of 2.5-mg dose
-
Last dose: 2.5 mg (Cycle 1 Day 8)
- ≤2 weeks: Administer glofitamab 10 mg (Cycle 1 Day 15), then resume planned treatment schedule
- >2 to ≤4 weeks: Repeat glofitamab 2.5 mg (Cycle 1 Day 8); then administer glofitamab 10 mg (Cycle 1 Day 15) and resume planned treatment schedule
- >4 weeks: Repeat obinutuzumab 1,000 mg pretreatment (Cycle 1 Day 1) and glofitamab 2.5 mg (Cycle 1 Day 8); then administer glofitamab 10 mg (Cycle 1 Day 15) and resume planned treatment schedule
- Hospitalize patient during and for 24 hr after completing infusion of 2.5-mg dose
- Hospitalize during and for 24 hr after completing infusion of 10-mg dose if CRS occurred during most recent 2.5-mg dose
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Glofitamab 10 mg (Cycle 1 Day 15)
- ≤2 weeks: Administer glofitamab 30 mg (Cycle 2 Day 1), and then resume the planned treatment schedule
- >2 to ≤6 weeks: Repeat glofitamab 10 mg (Cycle 1 Day 15), then administer glofitamab 30 mg (Cycle 2 Day 1) and resume planned treatment schedule
- >6 weeks: Repeat obinutuzumab 1,000 mg pretreatment (Cycle 1 Day 1), glofitamab 2.5 mg (Cycle 1 Day 8), and glofitamab 10 mg (Cycle 1 Day 15); then administer glofitamab 30 mg (Cycle 2 Day 1) and resume planned treatment schedule
- Hospitalize patient during and for 24 hr after completing infusion of 2.5-mg dose
- Hospitalize during and for 24 hr after completing infusion of 10-mg dose if CRS occurred during most recent 2.5-mg dose
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Glofitamab 30 mg (Cycle 2 onwards)
- ≤6 weeks: Administer glofitamab 30 mg, then resume planned treatment schedule
- >6 weeks: Repeat Cycle 1 regimen obinutuzumab 1,000 mg pretreatment (Day 1), glofitamab 2.5 mg (Day 8), and glofitamab 10 mg (Day 15), then administer glofitamab 30 mg (Day 1 of next cycle) and resume planned treatment schedule
- Hospitalize patient during and for 24 hr after completing infusion of 2.5-mg dose
- Hospitalize during and for 24 hr after completing infusion of 10-mg dose if CRS occurred during most recent 2.5-mg dose
Storage
Unopened vials
- Refrigerate at 2-8ºC (36-46ºF); in original carton to protect from light
- Do not freeze
- Do not shake
Diluted solutions
- If not immediately used, refrigerate at 2-8ºC (36-46ºF) for up to 64 hr, or store at room temperature up to 25ºC (77ºF) for up to 4 hr
- Do not freeze
- Discard diluted infusion solution if storage time exceeds these limits
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Images
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Formulary
FormularyPatient Discounts
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Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.
