Glofitamab: Drug information

ALERT: US Boxed Warning

Cytokine release syndrome

Cytokine release syndrome (CRS), including serious or fatal reactions, can occur in patients receiving glofitamab. Premedicate before each dose, and initiate treatment with the glofitamab step-up dosing schedule to reduce the risk of CRS. Withhold glofitamab until CRS resolves or permanently discontinue based on severity.

Dosing: Adult

Note: Ensure patients are well-hydrated prior to glofitamab administration. Avoid administering glofitamab to patients with active infection. Should only be administered by a qualified provider with appropriate medical support to manage severe cytokine release syndrome (CRS). The manufacturer recommends hospitalization during infusion and for 24 hours following completion of step-up dose 1 (2.5 mg on day 8 of cycle 1). Patients who experienced CRS (any grade) during step-up dose 1 should be hospitalized during infusion and for 24 hours following completion of step-up dose 2 (10 mg on day 15 of cycle 1). CRS may occur with step-up dose 2 in patients who did not experience CRS with step-up dose 1. Patients who experienced ≥ grade 2 CRS with the previous infusion should be hospitalized during infusion and for 24 hours following completion of the next glofitamab infusion.

Premedication: Premedicate prior to each glofitamab dose. See "Glofitamab Recommended Premedications" table.

Prophylaxis: Administer antimicrobial prophylaxis according to guidelines. Consider prophylaxis for pneumocystis jirovecii pneumonia prior to initiating glofitamab. Consider initiating herpes virus prophylaxis prior to initiating glofitamab to prevent herpes zoster reactivation. Consider prophylaxis for cytomegalovirus infection (in patients at increased risk). Administer antihyperuricemics and ensure adequate hydration in patients at risk for tumor lysis syndrome.

Diffuse large B-cell lymphoma, relapsed or refractory

Diffuse large B-cell lymphoma, relapsed or refractory: IV:

Note: Administer pretreatment with a single obinutuzumab dose on cycle 1, day 1 (7 days prior to the first glofitamab dose) to deplete B cells (circulating and lymphoid tissue).

**Glofitamab IV Dosing Schedule^{a, b} (21-day treatment cycles)**
Cycle number	Day of treatment	Glofitamab dose^band infusion duration
^a Continue for a maximum of 12 cycles (including cycle 1 step-up dosing) or until disease progression or unacceptable toxicity (whichever occurs first).
^b Manufacturer’s labeling, Dickinson 2022.
^c Refer to obinutuzumab monograph for dosing.
^d May extend the infusion duration up to 8 hours if cytokine release syndrome (CRS) was experienced with the previous glofitamab dose.
^e Maintain an infusion duration of 4 hours if CRS was experienced with the previous glofitamab dose.
Cycle 1	Day 1	Administer obinutuzumab^c
	Day 8	2.5 mg (step-up dose 1) over 4 hours
	Day 15	10 mg (step-up dose 2) over 4 hours^d
Cycle 2	Day 1	30 mg over 4 hours^d
Cycles 3 to 12^a	Day 1	30 mg over 2 hours^e

**Glofitamab Recommended Premedications**
Cycle/Treatment day	Patients requiring premedication	Premedication	Administration schedule
^aIf dexamethasone is not available, may use prednisone 100 mg, prednisolone 100 mg, or methylprednisolone 80 mg IV.
^b CRS = cytokine release syndrome.
Cycle 1 (days 8 and 15); cycle 2; cycle 3	All patients	Dexamethasone 20 mg IV^a	Complete at least 1 hour prior to glofitamab infusion.
		Acetaminophen 500 to 1,000 mg orally	At least 30 minutes prior to glofitamab infusion.
		Antihistamine (diphenhydramine 50 mg orally or IV or equivalent)	Complete at least 30 minutes prior to glofitamab infusion.
All subsequent infusions	All patients	Acetaminophen 500 to 1,000 mg orally	At least 30 minutes prior to glofitamab infusion.
	All patients	Antihistamine (diphenhydramine 50 mg orally or IV or equivalent)	Complete at least 30 minutes prior to glofitamab infusion.
	Patients who experienced CRS^b (any grade) with the previous dose	Dexamethasone 20 mg IV^a	Complete at least 1 hour prior to glofitamab infusion.

Missed or delayed doses: If a glofitamab dose is missed or delayed, restart based on the table.

**Recommendations for Restarting Glofitamab IV After a Dosing Delay**
Last dose administered	Time since last dose	Action for next glofitamab dose(s)^a
^a Administer premedications prior to glofitamab dose and monitor appropriately.
^b Patients should be hospitalized during and for 24 hours after the glofitamab 2.5 mg dose.
^c Patients should be hospitalized during and for 24 hours after the glofitamab 10 mg dose if cytokine release syndrome (any grade) occurred with the most recent glofitamab 2.5 mg dose.
Cycle 1, day 1 (obinutuzumab)	≤2 weeks	Administer glofitamab 2.5 mg (cycle 1 day 8)^b then resume the planned treatment schedule.
Cycle 1, day 1 (obinutuzumab)	>2 weeks	Repeat obinutuzumab pretreatment dose, then administer glofitamab 2.5 mg (cycle 1 day 8)^b and resume the planned treatment schedule.
Cycle 1, day 8 (glofitamab 2.5 mg)	≤2 weeks	Administer glofitamab 10 mg (cycle 1 day 15)^c then resume the planned treatment schedule.
	>2 to ≤4 weeks	Repeat glofitamab 2.5 mg (cycle 1 day 8),^b then administer glofitamab 10 mg (cycle 1 day 15)^c and resume the planned treatment schedule.
	>4 weeks	Repeat obinutuzumab pretreatment dose and glofitamab 2.5 mg (cycle 1 day 8),^b then administer glofitamab 10 mg (cycle 1 day 15)^c and resume the planned treatment schedule.
Cycle 1, day 15 (glofitamab 10 mg)	≤2 weeks	Administer glofitamab 30 mg (cycle 2 day 1) then resume the planned treatment schedule.
	>2 to ≤6 weeks	Repeat glofitamab 10 mg (cycle 1 day 15),^c then administer glofitamab 30 mg (cycle 2 day 1) and resume the planned treatment schedule.
	>6 weeks	Repeat obinutuzumab pretreatment dose, glofitamab 2.5 mg (cycle 1 day 8),^b and glofitamab 10 mg (cycle 1 day 15),^c then administer glofitamab 30 mg (cycle 2 day 1) and resume the planned treatment schedule.
Cycle 2 and beyond (glofitamab 30 mg)	≤6 weeks	Administer glofitamab 30 mg and resume the planned treatment schedule.
Cycle 2 and beyond (glofitamab 30 mg)	>6 weeks	Repeat cycle 1 regimen (obinutuzumab day 1, glofitamab 2.5 mg day 8,^b glofitamab 10 mg day 15^c), then administer glofitamab 30 mg (day 1 of the next cycle) and resume the planned treatment schedule.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

Note: Kidney function estimated using the Cockcroft-Gault equation.

CrCl 30 to <90 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling; however, no clinically significant difference in glofitamab pharmacokinetics was observed based on CrCl 30 to <90 mL/minute.

CrCl 15 to <30 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling (effects on glofitamab pharmacokinetics are unknown).

End-stage kidney disease (CrCl <15 mL/minute): There are no dosage adjustments provided in the manufacturer’s labeling (effects on glofitamab pharmacokinetics are unknown).

Dosing: Hepatic Impairment: Adult

Mild impairment (total bilirubin >1 to 1.5 times ULN or AST > ULN): There are no dosage adjustments provided in the manufacturer’s labeling; however, no clinically significant difference in glofitamab pharmacokinetics was observed based on mild hepatic impairment.

Moderate or severe impairment (total bilirubin >1.5 times ULN and any AST): There are no dosage adjustments provided in the manufacturer’s labeling (effects on glofitamab pharmacokinetics are unknown).

Dosing: Obesity: Adult

American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m²: The dosing in the FDA-approved prescribing information should be followed in all patients, regardless of obesity status. If a patient with a BMI ≥30 kg/m² experiences high-grade toxicity from systemic anticancer therapy, the same dosage modification recommendations should be followed for all patients, regardless of obesity status (Ref).

Dosing: Adjustment for Toxicity: Adult

Refer to "Dosing: Adult" for recommendations on restarting glofitamab after dose delays.

Cytokine release syndrome: If cytokine release syndrome (CRS) is suspected, interrupt glofitamab until CRS resolves; manage according to the table below and per clinical practice guidelines. Identify CRS based on the clinical presentation. Evaluate for other causes of fever, hypotension, and hypoxia, and manage appropriately. Supportive therapy for CRS may include intensive care for severe or life-threatening CRS.

**Glofitamab-Related CRS Management^d**
CRS grade	Presenting symptoms	Actions
^aFever may be masked by premedications; if clinical presentation is consistent with CRS, follow CRS management recommendations.
^bInfusion duration may be extended up to 8 hours (as appropriate) for that cycle.
^cRefer to "Dosing: Adult" for recommendations for restarting glofitamab after a dosing delay.
^dCRS = cytokine release syndrome; CPAP = continuous positive airway pressure; BiPAP = bilevel positive airway pressure.
Grade 1	Temperature ≥38°C (100.4°F),^a attributed to CRS.	Withhold glofitamab and manage per practice guidelines. If symptoms resolve, restart infusion at a slower rate.^b Ensure CRS symptoms are resolved for at least 72 hours prior to the next glofitamab dose.^c Consider a slower infusion rate for the next dose.
Grade 2	Temperature ≥38°C (100.4°F)^awith: Hypotension not requiring vasopressors and/or Hypoxia requiring low-flow oxygen (<6 L/minute) via nasal cannula or blow-by.	Withhold glofitamab and manage per practice guidelines. If symptoms resolve, restart infusion at a slower rate.^b Ensure CRS symptoms are resolved for at least 72 hours prior to the next glofitamab dose.^c For the next dose, consider a slower infusion rate, monitor more frequently, and consider hospitalization. For recurrent grade 2 CRS, manage per grade 3 CRS.
Grade 3	Temperature ≥38°C (100.4°F)^a with: Hypotension requiring a vasopressor (with or without vasopressin) and/or Hypoxia requiring high-flow oxygen (≥6 L/minute) via nasal cannula, face mask, non-rebreather mask, or Venturi mask.	Withhold glofitamab and manage per practice guidelines, which may include intensive care. Ensure CRS symptoms are resolved for at least 72 hours prior to the next glofitamab dose.^c Hospitalize for the next glofitamab dose, monitor more frequently, and consider a slower infusion rate.^b For recurrent grade 3 CRS, permanently discontinue glofitamab.
Grade 4	Temperature ≥38°C (100.4°F)^a with: Hypotension requiring multiple vasopressors (excluding vasopressin) and/or Hypoxia requiring oxygen via positive pressure (eg, CPAP, BiPAP,^d intubation, and mechanical ventilation).	Permanently discontinue glofitamab. Manage CRS per practice guidelines and provide supportive therapy, which may include intensive care.

Neurologic toxicity: At the first sign of neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), consider withholding glofitamab and obtaining a neurology evaluation (based on the type and severity of neurotoxicity). Rule out other causes of neurologic symptoms. Provide supportive care (which may include intensive care).

**Glofitamab-Related Neurologic Toxicity Management (Including ICANS^e)**
Adverse reaction	Severity	Actions
^a Based on the American Society of Transplantation and Cellular Therapy (ASTCT) 2019 grading for ICANS.
^bConsider the type of neurotoxicity prior to deciding to withhold glofitamab.
^c Refer to "Dosing: Adult" for recommendations for restarting glofitamab after a dosing delay.
^d Evaluate risks versus benefits prior to resuming glofitamab.
^eICANS = immune effector cell-associated neurotoxicity syndrome.
Neurologic toxicity (including ICANS^a)	Grade 1	Continue glofitamab and monitor neurologic toxicity symptoms. If ICANS, manage per practice guidelines.
	Grade 2	Withhold glofitamab until neurologic toxicity symptoms improve to grade 1 or baseline.^{b, c} Provide supportive therapy and consider neurologic evaluation. If ICANS, manage per practice guidelines.
	Grade 3	Withhold glofitamab until neurologic toxicity symptoms improve to grade 1 or baseline for at least 7 days.^{c, d} For grade 3 neurologic events lasting >7 days, consider permanently discontinuing glofitamab. Provide supportive therapy and consider neurology evaluation. If ICANS, manage per practice guidelines.
	Grade 4	Permanently discontinue glofitamab. Provide supportive therapy, which may include intensive care; consider neurology evaluation. If ICANS, manage per practice guidelines.

**Recommended Glofitamab Dosage Modifications for Other Adverse Reactions**
Adverse reaction	Severity	Actions
^aRefer to "Dosing: Adult" for recommendations for restarting glofitamab after a dosing delay.
Hematologic toxicity	ANC <500/mm³	Withhold glofitamab until ANC is ≥500/mm³.^a
Hematologic toxicity	Platelets <50,000/mm³	Withhold glofitamab until platelets are ≥50,000/mm³.^a
Infections	Grades 1 to 4	Withhold glofitamab or consider permanently discontinuing based on severity. Manage infection appropriately and as clinically indicated. Withhold glofitamab in patients with active infection until infection resolves.^a For grade 4 infection, consider permanently discontinuing glofitamab.
Tumor flare	Grades 2 to 4	Monitor for signs/symptoms of compression or obstruction due to mass effect secondary to tumor flare. Institute appropriate management, including antihistamines and corticosteroids. Withhold glofitamab until tumor flare resolves.^a
Other adverse reactions	Grade 3 or higher	Withhold glofitamab until adverse reaction resolves to grade 1 or baseline.^a

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%:

Dermatologic: Skin rash (20%)

Endocrine & metabolic: Decreased serum calcium (48%), decreased serum phosphate (69%), decreased serum potassium (32%), decreased serum sodium (49%), hypouricemia (23%)

Gastrointestinal: Constipation (14%), diarrhea (14%)

Hematologic & oncologic: Decreased hemoglobin (72%; grades 3/4: 8%), decreased neutrophils (56%; grades 3/4: 26%), decreased platelet count (56%; grades 3/4: 8%), decreased serum fibrinogen (84%; grades 3/4: 21%), lymphocytopenia (90%; grades 3/4: 83%), tumor flare (12%; grades 3/4: 3%)

Hepatic: Increased gamma-glutamyl transferase (33%)

Hypersensitivity: Cytokine release syndrome (70%)

Infection: Serious infection (16%; including sepsis [4%])

Nervous system: Fatigue (20%)

Neuromuscular & skeletal: Musculoskeletal pain (21%)

Miscellaneous: Fever (16%)

1% to 10%:

Cardiovascular: Edema (10%)

Gastrointestinal: Abdominal pain (10%), gastrointestinal hemorrhage, nausea (10%), vomiting

Hematologic & oncologic: Febrile neutropenia (3%), tumor lysis syndrome

Hypersensitivity: Infusion-related reactions

Infection: Herpes zoster infection

Nervous system: Neurotoxicity (dizziness [≤7%], headache [10%], immune effector cell-associated neurotoxicity [ICANS] [5%], mental status changes [cognitive dysfunction, confusion, delirium, disorientation, drowsiness: 5%], peripheral neuropathy [8%], vertigo [≤7%]), tremor

Neuromuscular & skeletal: Myelitis

Respiratory: Pneumonia, upper respiratory tract infection

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Warnings/Precautions

Concerns related to adverse effects:

• Cytokine release syndrome: Glofitamab may cause serious and fatal cytokine release syndrome (CRS). CRS occurred commonly in the clinical trial, with grade 1 CRS developing in over ½ of all patients, grade 2 in 14%, grade 3 in ~3%, and grade 4 in ~1% of patients. The most common manifestations of CRS included fever, tachycardia, hypotension, chills, and hypoxia. CRS occurred after the 2.5 mg glofitamab dose in over ½ of the patients, after the 10 mg dose in ~¹/₃ of patients, in ~¹/₃ of patients with the initial 30 mg dose, and with subsequent doses in a small percentage of patients. With the first step-up dose, the median time to onset of CRS (from the start of infusion) was 14 hours (range: 5 to 74 hours). CRS after any dose resolved in most cases, with a median duration of 2 days (range: 1 to 14 days). Recurrent CRS occurred in ~¹/₃ of all patients. In patients where CRS first occurred with the 10 mg dose, events were predominantly grade 1, but cases of grades 2 and 3 also occurred. Glofitamab should be administered in a facility equipped to monitor and manage CRS and should be initiated according to the step-up dosing schedule to reduce the risk of CRS. Administer pretreatment medications and ensure adequate hydration. The initial dose requires hospitalization; the second step-up dose and subsequent doses may also require hospitalization (if ≥ grade 2 CRS occurred with the prior dose).

• Infections: Glofitamab may cause serious or fatal infections; grade 3 and 4 infections (including COVID-19 infections) were observed. COVID-19 infections included pneumonia and sepsis. Neutropenic fever was also reported.

• Neurologic toxicity: Glofitamab may cause serious and fatal neurologic toxicity, including immune effector cell-associated neurotoxicity (ICANS). The most frequent neurologic toxicities of any grade were headache, peripheral neuropathy, dizziness/vertigo, and mental status changes (including confusion, cognitive disorder, disorientation, somnolence, and delirium). Grade 3 or higher neurologic adverse reactions included somnolence, delirium, and myelitis and occurred in a small percentage of patients. Cases of ICANS (any grade) occurred in ~5% of patients. The risk of neurologic toxicity may be increased if glofitamab is administered with other products that also cause dizziness or mental status changes. Optimize concurrent medications and hydration to avoid dizziness or mental status changes. Institute appropriate fall precautions. Patients who are affected should refrain from driving and/or engaging in hazardous occupations or activities, such as operating heavy/potentially dangerous machinery until the neurologic toxicity fully resolves.

• Tumor flare: Glofitamab may cause serious tumor flare; grade 2 and 3 events have been reported. Tumor flare manifestations include localized pain and swelling at the sites of the lymphoma lesions and/or dyspnea from new pleural effusions. Cases of recurrent tumor flare have occurred. Most tumor flare events occurred during cycle 1, with a median time to first onset of 2 days (range: 1 to 16 days) after the first glofitamab dose; the median duration was 3.5 days (range: 1 to 35 days).

Special populations:

• Older adults: Patients ≥65 years of age experienced a higher rate of fatal adverse reactions (primarily from COVID-19 infections), compared to patients <65 years of age.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous [preservative free]:

Columvi: Glofitamab-gxbm 10 mg/10 mL (1 mg/mL) (10 mL); Glofitamab-gxbm 2.5 mg/2.5 mL (1 mg/mL) (2.5 mL)

Generic Equivalent Available: US

No

Pricing: US

Solution (Columvi Intravenous)

2.5 mg/2.5 mL (per mL): $1,226.28

10 mg/10 mL (per mL): $1,226.28

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Columvi: Glofitamab-gxbm 10 mg/10 mL (1 mg/mL) (10 mL); Glofitamab-gxbm 2.5 mg/2.5 mL (1 mg/mL) (2.5 mL)

Prescribing and Access Restrictions

Glofitamab is available through specialty distributors and wholesalers. Distribution information is available at https://www.genentech-access.com/hcp/brands/columvi/learn-about-our-services/product-distribution.html or at 1-877-436-3683.

Administration: Adult

IV: Infuse cycles 1 and 2 over 4 hours; may begin infusing over 2 hours in cycle 3 in the absence of cytokine release syndrome (CRS). Infusion time may need to be extended up to 8 hours if CRS was experienced with the prior dose. Administer via a dedicated line with a 0.2 micron in-line filter. Glofitamab should be administered by a health care provider with immediate access to appropriate medical support, including supportive medications for managing CRS.

No incompatibilities have been observed with infusion sets with product-contacting surfaces of polyurethane (PUR), polyvinyl chloride, or polyethylene, and in-line filter membranes composed of polyether sulfone or polysulfone.

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761309s000lbl.pdf#page=19, must be dispensed with this medication.

Use: Labeled Indications

Diffuse large B-cell lymphoma, relapsed or refractory: Treatment of relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified or large B-cell lymphoma arising from follicular lymphoma in adults after 2 or more lines of systemic therapy.

Medication Safety Issues

Sound-alike/look-alike issues

Glofitamab may be confused with epcoritamab, naxitamab, tafasitamab.

High alert medication

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

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.

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy

Antithymocyte Globulin (Equine): Anti-CD20 B-Cell Depleting Therapies may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of anti-CD20 B-cell depleting therapy is reduced. Anti-CD20 B-Cell Depleting Therapies may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy

Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG Products: Anti-CD20 B-Cell Depleting Therapies may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid combination

Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy

Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination

Chikungunya Vaccine (Live): Anti-CD20 B-Cell Depleting Therapies may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy

Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination

Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification

COVID-19 Vaccines: Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of COVID-19 Vaccines. Management: Administer COVID-19 vaccine 2 to 4 weeks prior to the next scheduled dose of anti-CD20 therapy, if used chronically for the treatment of autoimmune disease. Revaccinate 6 months after completion of anti-CD20 therapy if used over a limited period. Risk D: Consider therapy modification

CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors): Glofitamab may increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification

Dengue Tetravalent Vaccine (Live): Anti-CD20 B-Cell Depleting Therapies may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination

Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification

Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination

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

Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination

Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy

Influenza Virus Vaccines: Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines 2 weeks prior to starting anti-CD20 B-cell depleting therapies. Vaccination of patients treated with these agents in the past 6 months is not recommended. Risk D: Consider therapy modification

Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification

Mumps- Rubella- or Varicella-Containing Live Vaccines: Anti-CD20 B-Cell Depleting Therapies may enhance the adverse/toxic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination

Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination

Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination

Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy

Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy

Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy

Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy

Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Poliovirus Vaccine (Live/Trivalent/Oral): Anti-CD20 B-Cell Depleting Therapies may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination

Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Rabies Vaccine: Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification

Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination

Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification

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

Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination

Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification

Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy

Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination

Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination

Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination

Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination

Typhoid Vaccine: Anti-CD20 B-Cell Depleting Therapies may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination

Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy

Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination

Vaccines (Inactivated/Non-Replicating): Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation or 6 months after anti-CD20 B-cell depleting therapies. If vaccinated prior to B cell recovery, consider assessing immune response to vaccination. Risk D: Consider therapy modification

Vaccines (Live): Anti-CD20 B-Cell Depleting Therapies may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination

Yellow Fever Vaccine: Anti-CD20 B-Cell Depleting Therapies may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination

Reproductive Considerations

Verify pregnancy status prior to treatment initiation. Patients who could become pregnant should use effective contraception during therapy and for 1 month after the last glofitamab dose.

Pregnancy Considerations

Glofitamab is a humanized monoclonal antibody (IgG₁). Human IgG crosses the placenta. Fetal exposure is dependent upon the IgG subclass, maternal serum concentrations, placental integrity, newborn birth weight, and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis and the highest during the third trimester (Clements 2020; Palmeira 2012; Pentsuk 2009).

Animal reproduction studies have not been conducted. Based on the mechanism of action, in utero exposure to glofitamab may cause fetal harm.

Breastfeeding Considerations

It is not known if glofitamab is present in breast milk.

Glofitamab is a humanized monoclonal antibody (IgG₁). Human IgG is present in breast milk; concentrations are dependent upon IgG subclass and postpartum age (Anderson 2021).

Breastfeeding is not recommended by the manufacturer during therapy and for 1 month after the last glofitamab dose.

Monitoring Parameters

Monitor blood counts. Verify pregnancy status prior to treatment (in patients who could become pregnant). Monitor for signs/symptoms of cytokine release syndrome (CRS); at the first sign of CRS, immediately evaluate patients for hospitalization. Monitor for signs/symptoms of neurologic toxicity; promptly evaluate patients who experience neurologic toxicity (eg, tremors, dizziness, or adverse reactions that may impair cognition or consciousness), including potential neurology evaluation. Monitor for infections (before and during glofitamab treatment). Monitor for tumor flare; patients with bulky tumors or disease located in close proximity to airways or a vital organ should be monitored closely during initial therapy; monitor for signs/symptoms of compression or obstruction due to mass effect secondary to tumor flare. Assess risk for and monitor for signs/symptoms of tumor lysis syndrome.

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Mechanism of Action

Glofitamab is a bispecific T-cell engaging antibody that targets CD3 and CD20; a novel 2:1 tumor–T-cell binding configuration confers bivalency for CD20 and monovalency for CD3 (Dickinson 2022). Glofitamab binds to CD20 expressed on the surface of B-cells and to the CD3 receptor expressed on T-cell surfaces, resulting in T-cell activation and proliferation, cytokine secretion, and lysis of CD20-expressing B cells.

Pharmacokinetics (Adult Data Unless Noted)

Onset: Circulating B cells decreased to undetectable levels by cycle 1, day 10 (following obinutuzumab pretreatment and step-up glofitamab dose 1) in a majority of patients.

Distribution: V_d: 5.6 L.

Metabolism: Metabolized into small peptides via catabolic pathways.

Half-life elimination: 7.6 days.

Excretion: Clearance: 0.617 L/day (at steady state).

خرید پکیج

Glofitamab: Drug information