AHFS Class:

• Antineoplastic Agents 10:00

Generic Name(s):

• Glofitamab-gxbm

Glofitamab-gxbm, a bispecific CD20-directed CD3 T-cell engager, is an antineoplastic agent.1

Diffuse Large B-cell Lymphoma or Large B-cell Lymphoma Arising From Follicular Lymphoma

Glofitamab-gxbm is used for the treatment of adult patients with 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.1

This indication is approved under accelerated approval based on response rate and durability of response.1 Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).1

Clinical Experience

The safety and efficacy of glofitamab-gxbm for the treatment of relapsed or refractory DLBCL, NOS and LBCL arising from follicular lymphoma were established in a phase 1/2, open-label, multicenter, multicohort, single-arm study (Study NP30179).1,  2 Adults with relapsed or refractory LBCL after ≥2 lines of systemic therapy were included if they also had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, absolute neutrophil count (ANC) ≥1500/mm³, platelet count ≥75,000/mm³ independent of transfusion, serum creatinine ≤1.5 times the upper limit of normal (ULN) or creatinine clearance ≥50 mL/minute, and hepatic transaminases ≤3 times the ULN.1,  2 Patients were excluded if they had active or previous CNS lymphoma or disease, acute infection, recent infection requiring IV antibiotics, or prior allogeneic hematopoietic stem cell transplantation (HCST).1 The protocol-defined primary efficacy endpoint was complete response (CR) rate.2,  3 However, for regulatory purposes, FDA's primary efficacy endpoint was objective response rate (ORR) and duration of response (DOR), as determined by an Independent Review Committee (IRC) using the 2014 Lugano criteria.1,  3 Following pretreatment with obinutuzumab on Cycle 1 Day 1, glofitamab-gxbm was administered via IV infusion in 21-day cycles for up to 12 cycles, unless patients experienced disease progression or unacceptable toxicity.1,  2 Glofitamab-gxbm was administered in a step-up dosing schedule; on Cycle 1 Day 8, patients received glofitamab-gxbm 2.5 mg followed by 10 mg on Cycle 1 Day 15.1,  2 On Cycle 2 Day 1 and on Day 1 of each subsequent cycle, patients received 30 mg.1,  2

A total of 155 patients with relapsed or refractory LBCL were enrolled to receive glofitamab-gxbm.2 Efficacy was evaluated in a modified intention-to-treat population, including 132 patients with de novo DLBCL, NOS (80%) or LBCL arising from follicular lymphoma (20%) who received at least 1 dose of glofitamab-gxbm.1,  3 The median age was 67 years (range: 21-90 years); the majority were male (64%) and White (77%).1 The median number of prior lines of systemic therapy was 3 (range: 2-7); 30% previously received chimeric antigen receptor (CAR) T-cell therapy and 19% previously received autologous HSCT.1 The majority of patients (83%) had refractory disease to the last therapy, while 55% had primary refractory disease.1

The ORR was 56% (74/132 patients).1 A CR was achieved in 57 patients (43%) and a partial response was achieved in 17 patients (13%).1 The median time to first response was 42 days (range: 31-178 days).1 The median DOR was 18.4 months.1

Clinical Perspective

The National Comprehensive Cancer Network (NCCN) published a focused manuscript detailing the management of B-cell lymphomas.4 There are various treatment options available for patients with relapsed/refractory DLBCL, and choice of therapy for an individual patient is dependent upon various factors including prior treatments and DOR.4 In general, therapeutic options for previously treated DLBCL include chemoimmunotherapy, autologous HSCT (for eligible patients), antibody-drug conjugates, CAR T-cell therapies, and/or bispecific T-cell engagers.4 There are currently two CD20-directed bispecific T-cell engagers approved for the treatment of DLBCL in the third-line setting.1,  4 The NCCN recommends glofitamab-gxbm and epcoritamab-bysp, without indicating a preference between the two agents, for patients with relapsed/refractory DLBCL after ≥2 prior therapies.1,  4

General

Pretreatment Screening

• Verify pregnancy status in females of reproductive potential.1

Patient Monitoring

• Monitor for signs of cytokine release syndrome (CRS).1
• Hospitalize patients in a facility equipped to monitor for and manage CRS during administration and for 24 hours following step-up dose 1 (2.5 mg; Cycle 1 Day 8).1 Hospitalize during step-up dose 2 (10 mg; Cycle 1 Day 15) if any grade CRS occurs during step-up dose 1.1 Hospitalize during subsequent infusions if Grade ≥2 CRS occurred with the previous infusion and for 24 hours after the next infusion.1
• Monitor for signs of neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS).1
• Monitor for signs and symptoms of tumor lysis syndrome (TLS).1
• Monitor before and during treatment for infection.1
• Monitor patients for signs of hematologic toxicity, including neutropenia and/or thrombocytopenia.1
• Patients with bulky tumors or disease located in close proximity to airways or a vital organ should be monitored closely during initial therapy for signs and symptoms of compression or obstruction due to mass effect secondary to tumor flare.1

Premedication and Prophylaxis

• Administer hyperuricemics to patients at risk of TLS, ensure adequate hydration status, and monitor as appropriate.1
• Consider initiation of antiviral prophylaxis to prevent herpes virus reactivation.1
• Consider initiation of prophylaxis for cytomegalovirus infection in patients at increased risk.1
• Consider initiation of prophylaxis for pneumocystis jirovecii Pneumonia (PJP) in patients at increased risk.1
• To deplete the circulating and lymphoid tissue cells, all patients should be pretreated with a single dose of obinutuzumab 1000 mg IV on Cycle 1 Day 1, 7 days prior to initiation of glofitamab-gxbm.1
• To reduce the risk of CRS and infusion-related reactions, prior to glofitamab-gxbm administration during Cycle 1 (Day 8 and Day 15) and Cycles 2-3, all patients should be premedicated with dexamethasone 20 mg (or equivalent) IV ≥1 hour prior to the infusion, oral acetaminophen 500-1000 mg, and an antihistamine (diphenhydramine 50 mg [or equivalent] IV or oral) ≥30 minutes prior to the infusion.1 For all subsequent infusions (Cycle 4 and beyond), all patients should be premedicated with oral acetaminophen 500-1000 mg and an antihistamine (diphenhydramine 50 mg [or equivalent] IV or oral) ≥30 minutes prior to the infusion.1 Patients who experienced any grade CRS with the previous dose should also be premedicated with dexamethasone 20 mg (or equivalent) IV ≥1 hour prior to the infusion.1

Administration

Administer glofitamab-gxbm via IV infusion in a dedicated line with a low protein-binding 0.2-micron in-line filter in a healthcare setting with immediate access to medical support to manage CRS, including severe CRS.1

Glofitamab-gxbm is available as 2.5 mg/2.5 mL and 10 mg/10 mL single-dose vials of preservative-free, colorless, clear solution that must be diluted prior to IV infusion.1

Prime the infusion line with the diluted infusion solution.1

Prepare the infusion solution in an IV bag or syringe.1 Once the infusion is complete, replace the empty infusion bag or syringe with an infusion bag or syringe containing 0.9% or 0.45% sodium chloride injection connected to the same line and continue the infusion at the same rate until the recommended infusion duration is reached1

Do not administer in glofitamab-gxbm in the same IV line with other medications.1

Store vials of glofitamab-gxbm refrigerated at 2-8°C in original carton to protect from light.1 Do not freeze.1 Do not shake.1

Glofitamab-gxbm is compatible with 0.9% sodium chloride and 0.45% sodium chloride.1

Dilution

Preparation of IV Infusion Bag

• Determine the dose, total volume of solution, and number of glofitamab-gxbm vials needed.1 Select an appropriate size infusion bag of 0.9% or 0.45% sodium chloride injection.1 If diluted with 0.9% sodium chloride injection, glofitamab-gxbm is compatible with polyvinyl chloride (PVC), polyethylene (PE), polypropylene (PP), or polyolefin IV infusion bags.1 If diluted with 0.45% sodium chloride injection, glofitamab-gxbm is compatible with PVC IV infusion bags.1
• Using aseptic technique, prepare the infusion by withdrawing and discarding the volume from the infusion bag as described in Table 1.1 Withdraw the required volume of glofitamab-gxbm and dilute into the infusion bag; discard any unused glofitamab-gxbm remaining in the vial.1 The final concentration should be 0.1-0.6 mg/mL.1
• Gently invert the bag to mix; do not shake.1

Table 1. Dilution of Glofitamab-gxbm Into IV Infusion Bag1

Dose of glofitamab-gxbm	Size of 0.9% sodium chloride injection or 0.45% sodium chloride injection infusion bag	Volume to be withdrawn and discarded from the infusion bag	Volume of glofitamab-gxbm to be added to the infusion bag	Total volume to be infused
2.5 mg	50 mL	27.5 mL	2.5 mL	25 mL
10 mg	50 mL	10 mL	10 mL	50 mL
10 mg	100 mL	10 mL	10 mL	100 mL
30 mg	50 mL	30 mL	30 mL	50 mL
30 mg	100 mL	30 mL	30 mL	100 mL

Preparation of IV Syringe (2.5 mg Dose Preparation)

• Step-up dose 1 (2.5 mg) may be prepared in an IV syringe, rather than an infusion bag.1 Using aseptic technique, withdraw 22.5 mL of 0.9% or 0.45% sodium chloride injection into a 30 mL polypropylene syringe.1 Withdraw 2.5 mL of glofitamab-gxbm from the vial into a second syrin discard any unused glofitamab-gxbm remaining in the vial.1
• Attach a connector to the 2 syringes and transfer the glofitamab-gxbm into the 30 mL syringe.1 Disconnect the syringes, draw air into the syringe containing the glofitamab-gxbm diluted solution, and close.1 The final concentration should be 0.1 mg/mL.1
• Gently invert to mix; do not shake.1 Remove air bubbles from syringe prior to administration.1

Administer prepared solution immediately.1 If not used immediately, store prepared solution under refrigeration at 2-8ºC for ≤64 hours.1 The diluted glofitamab-gxbm solution may also be stored at room temperature 25ºC for ≤4 hours.1 Do not freeze.1 Inspect the solution for particulate matter or discoloration prior to administration.1 The solution should be clear and colorless; discard if the solution is cloudy, discolored, or contains visible particles.1

Rate of Administration

Cycles 1-2 of the prepared glofitamab-gxbm solution are administered via IV infusion over 4 hours.1 Cycles 3-12 are administered over 2 hours.1 Administration rate may be extended for patients who experience CRS with their previous dose.1 In Cycles 1-2, for patients who experience CRS with their previous dose, the time of infusion may be extended to ≤8 hours.1 In Cycles 3-12, for patients who experience CRS with their previous dose, the duration of infusion should be maintained at 4 hours.1

Dosage

Diffuse Large B-cell Lymphoma or Large B-cell Lymphoma Arising From Follicular Lymphoma

The recommended adult dosage of glofitamab-gxbm is described in Table 2.1 Glofitamab-gxbm initiation begins with a step-up dose schedule following pretreatment with obinutuzumab.1 Treatment cycles are 21 days and may be continued for a maximum of 12 cycles or until disease progression or unacceptable toxicity, whichever occurs first.1

Table 2. Recommended Glofitamab-gxbm Dose and Schedule (21-Day Treatment Cycles)1

Treatment Cycle	Day	Dose of Glofitamab-gxbm	Duration of Infusion
Cycle 1	Day 1	Obinutuzumab 1000 mg pre-treatment	Initial rate of obinutuzumab: 50 mg/hour; rate of infusion may be increased in 50 mg/hour increments every 30 minutes to a maximum of 400 mg/hour. Refer to the obinutuzumab prescribing information for complete dosing information.
Cycle 1	Day 8	Step-up dose 1 of glofitamab-gxbm: 2.5 mg	4 hours
Cycle 1	Day 15	Step-up dose 2 of glofitamab-gxbm: 10 mg	4 hours
Cycle 2	Day 1	Glofitamab-gxbm 30 mg	4 hours
Cycles 3-12	Day 1	Glofitamab-gxbm 30 mg	2 hours

Dosage Modification for Toxicity

No dosage reduction for glofitamab-gxbm is recommended.1 Patients who experience toxicity may require temporary interruption of therapy and/or permanent discontinuation of therapy, depending on severity.1 If restarting glofitamab-gxbm after a dose delay due to toxicity, follow dosage recommendations in Table 4.1

Cytokine Release Syndrome

Identify CRS based on clinical presentation.1 Evaluate for and treat other causes of fever, hypoxia, and hypotension.1 Premedication may mask fever.1 If CRS is suspected, withhold glofitamab-gxbm and manage according to the recommendations in Table 3 and current practice guidelines.1 Administer supportive care, which may include intensive care for severe or life-threatening cases.1

Severity of CRS is graded per the American Society for Transplantation and Cellular Therapy (ASTCT) 2019 consensus grading criteria.1

Table 3. Recommendations for Management of CRS1

Grade	Presenting Symptoms	Actions
Grade 1	Temperature ≥38°C	Withhold glofitamab-gxbm and manage per current practice guidelines. If symptoms resolve, restart infusion at a slower rate (duration of infusion may be extended up to 8 hours, as appropriate for that cycle). Ensure CRS symptoms are resolved for ≥72 hours before the next dose. Reference Table 4 when restarting glofitamab-gxbm after a dose delay due to toxicity. Consider slower infusion rate for the next dose.
Grade 2	Temperature ≥38°C with hypotension not requiring vasopressors and/or hypoxia requiring low-flow oxygen (<6 L/minute) by nasal cannula or blow-by	Withhold glofitamab-gxbm and manage per current practice guidelines. If symptoms resolve, restart infusion at a slower rate (duration of infusion may be extended up to 8 hours, as appropriate for that cycle). Ensure CRS symptoms are resolved for ≥72 hours before the next dose. Reference Table 4 when restarting glofitamab-gxbm after a dose delay due to toxicity. 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 with hypotension requiring vasopressor (with or without vasopressin) and/or hypoxia requiring high-flow oxygen (≥6 mL/minute) by nasal cannula, face mask, non-rebreather mask, or Venturi mask	Withhold glofitamab-gxbm and manage per current practice guidelines, which may include intensive care. Ensure CRS symptoms are resolved for ≥72 hours before the next dose. Reference Table 4 when restarting glofitamab-gxbm after a dose delay due to toxicity. For the next dose, hospitalize patient, monitor more frequently, and consider a slower infusion rate (duration of infusion may be extended up to 8 hours, as appropriate for that cycle). For recurrent Grade 3 CRS, permanently discontinue glofitamab-gxbm.
Grade 4	Temperature ≥38°C with hypotension requiring vasopressor (excluding vasopressin) and/or hypoxia requiring oxygen by positive pressure (e.g., continuous positive airway pressure [CPAP], bilevel positive airway pressure [BiPAP], intubation, and mechanical ventilation).	Permanently discontinue glofitamab-gxbm and manage per current practice guidelines, which may include intensive care.

Neurologic Toxicity, Including ICANS

At the first sign of neurologic toxicity, including ICANS, consider neurology evaluation and withholding glofitamab-gxbm based on the type and severity of neurotoxicity.1

Adverse reaction severity is graded per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03.1 Severity of ICANS is graded per the ASTCT 2019 consensus grading criteria.1

If Grade 1 neurologic toxicity occurs, continue glofitamab-gxbm and monitor neurologic toxicity symptoms.1 If ICANS occurs, manage per current practice guidelines.1

If Grade 2 neurologic toxicity occurs, withhold glofitamab-gxbm until neurologic toxicity symptoms improve to Grade 1 or baseline.1 Consider the type of neurologic toxicity before deciding to withhold glofitamab-gxbm.1 Reference Table 4 when restarting glofitamab-gxbm after a dose delay due to toxicity.1 Provide supportive therapy and consider neurologic evaluation.1 If ICANS, manage per current practice guidelines.1

If Grade 3 neurologic toxicity occurs, withhold glofitamab-gxbm until neurologic toxicity symptoms improve to Grade 1 or baseline for ≥7 days.1 Reference Table 4 when restarting glofitamab-gxbm after a dose delay due to toxicity.1 Evaluate benefit-risk before restarting glofitamab-gxbm.1 For Grade 3 neurologic events lasting >7 days, consider permanently discontinuing glofitamab-gxbm.1 Provide supportive therapy, and consider neurologic evaluation.1 If ICANS, manage per current practice guidelines.1

If Grade 4 neurologic toxicity occurs, permanently discontinue glofitamab-gxbm.1 Provide supportive therapy, which may include intensive care, and consider neurology evaluation.1 If ICANS, manage per current practice guidelines.1

Infections

If Grade 1-4 (per the NCI CTCAE) infection occurs, withhold glofitamab-gxbm until the infection resolves.1 Reference Table 4 when restarting glofitamab-gxbm after a dose delay due to toxicity.1 For Grade 4, consider permanent discontinuation of glofitamab-gxbm.1

Tumor Flare

If Grade 1 (per the NCI CTCAE) tumor flare occurs, monitor for signs and symptoms of compression or obstruction due to mass effect secondary to tumor flare.1

If Grade 2-4 tumor flare occurs, 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.1 Withhold glofitamab-gxbm until tumor flare resolves.1 Reference Table 4 when restarting glofitamab-gxbm after a dose delay due to toxicity.1

Hematologic Toxicity

If neutropenia (absolute neutrophil count [ANC] <500/mm³ occurs, withhold glofitamab-gxbm until ANC is ≥500/mm³.1 Reference Table 4 when restarting glofitamab-gxbm after a dose delay due to toxicity.1

If thrombocytopenia (platelet count <50,000/mm³) occurs, withhold glofitamab-gxbm until platelet count is ≥50,000/mm³.1 Reference Table 4 when restarting glofitamab-gxbm after a dose delay due to toxicity.1

Other Adverse Reactions

If Grade 3-4 (per the NCI CTCAE) adverse reactions occur, withhold glofitamab-gxbm until the toxicity resolves to Grade 1 or baseline.1 Reference Table 4 when restarting glofitamab-gxbm after a dose delay due to toxicity.1

Dose Delay

Table 4 provides recommendations for restarting glofitamab-gxbm following a dose delay due to toxicity.1 When repeating the 2.5 mg dose, hospitalize patients during and for 24 hours after completion of the glofitamab-gxbm infusion.1 When repeating the 10 mg dose, if any grade CRS occurred during the most recent 2.5 mg dose, hospitalize patients during and for 24 hours after completion of the glofitamab-gxbm infusion.1 Administer premedications prior to each dose of glofitamab-gxbm.1

Table 4. Recommendations for Restarting Glofitamab-gxbm After a Dose Delay1

Last Dose Administered	Time Since Last Dose Administered	Action for Next Dose(s)
Obinutuzumab pretreatment (Cycle 1 Day 1)	≤2 weeks	Administer glofitamab-gxbm 2.5 mg (Cycle 1 Day 8), then resume the planned treatment schedule.
Obinutuzumab pretreatment (Cycle 1 Day 1)	>2 weeks	Repeat obinutuzumab 1000 mg pretreatment (Cycle 1 Day 1). Administer glofitamab-gxbm 2.5 mg (Cycle 1 Day 8) and resume the planned treatment schedule.
Glofitamab-gxbm 2.5 mg (Cycle 1 Day 8)	≤2 weeks	Administer glofitamab-gxbm 10 mg (Cycle 1 Day 15), then resume the planned treatment schedule.
Glofitamab-gxbm 2.5 mg (Cycle 1 Day 8)	>2 to ≤4 weeks	Repeat glofitamab-gxbm 2.5 mg (Cycle 1 Day 8). Then, administer glofitamab-gxbm 10 mg (Cycle 1 Day 15) and resume the planned treatment schedule.
Glofitamab-gxbm 2.5 mg (Cycle 1 Day 8)	>4 weeks	Repeat obinutuzumab 1000 mg pretreatment (Cycle 1 Day 1) and glofitamab 2.5 mg (Cycle 1 Day 8). Then administer glofitamab-gxbm 10 mg (Cycle 1 Day 15) and resume the planned treatment schedule.
Glofitamab-gxbm 10 mg (Cycle 1 Day 15)	≤2 weeks	Administer glofitamab-gxbm 30 mg (Cycle 2 Day 1), then resume the planned treatment schedule.
Glofitamab-gxbm 10 mg (Cycle 1 Day 15)	>2 to ≤6 weeks	Repeat glofitamab-gxbm 10 mg (Cycle 1 Day 15). Then administer glofitamab-gxbm 30 mg (Cycle 2 Day 1) and resume the planned treatment schedule.
Glofitamab-gxbm 10 mg (Cycle 1 Day 15)	>6 weeks	Repeat obinutuzumab 1000 mg pretreatment (Cycle 1 Day 1), glofitamab-gxbm 2.5 mg (Cycle 1 Day 8), and glofitamab-gxbm 10 mg (Cycle 1 Day 15). Then administer glofitamab-gxbm 30 mg (Cycle 2 Day 1) and resume the planned treatment schedule.
Glofitamab-gxbm 30 mg (Cycle 2 onwards)	≤6 weeks	Administer glofitamab-gxbm 30 mg, then resume the planned treatment schedule.
Glofitamab-gxbm 30 mg (Cycle 2 onwards)	>6 weeks	Repeat the Cycle 1 regimen: obinutuzumab 1000 mg pretreatment (Day 1), glofitamab-gxbm 2.5 mg (Day 8), and glofitamab-gxbm 10 mg (Day 15). Then administer glofitamab-gxbm 30 mg (Day 1 of next cycle) and resume the planned treatment schedule.

Special Populations

Hepatic Impairment

The manufacturer makes no specific dosage recommendations for patients with hepatic impairment.1

Renal Impairment

The manufacturer makes no specific dosage recommendations for patients with renal impairment.1

Geriatric Patients

The manufacturer makes no specific dosage recommendations for geriatric patients ≥65 years of age.1

Contraindications

• None.1

Warnings/Precautions

Warnings

Cytokine Release Syndrome

A boxed warning regarding the risk of cytokine release syndrome (CRS) is included in the glofitamab-gxbm prescribing information.1 Cytokine release syndrome, including serious or fatal reactions, can occur in patients receiving glofitamab-gxbm.1

In clinical studies of glofitamab-gxbm in patients with relapsed or refractory LBCL, 70% of patients experienced any grade of CRS and 4.2% of patients experienced Grade 3 or 4 CRS.1 The majority of CRS cases occurred with step-up dose 1 (2.5 mg; 56% of patients), and 35% and 29% of cases occurred after step-up dose 2 (10 mg) and the first target dose (30 mg), respectively.1 The median time to onset was 14 hours (range: 5-74 hours) and the median duration was 2 days (range: 1-14 days).1 The most common manifestations of CRS included fever, tachycardia, hypotension, chills, and hypoxia.1 Recurrent CRS occurred in 34% of patients.1 The first CRS event can occur with step-up dose 2 (10 mg); 11% of patients experienced their first CRS event with step-up dose 2 (10 mg).1 CRS after any dose resolved in 98% of cases.1

Administer glofitamab-gxbm in a facility equipped to monitor and manage CRS.1 Initiate therapy according to the step-up dosing schedule, administer pretreatment medications, and ensure adequate hydration to reduce the risk of CRS.1 Patients should be hospitalized and closely monitored during and for 24 hours after completing the infusion of step-up dose 1 (2.5 mg).1 If CRS is suspected, withhold glofitamab-gxbm and manage according to the recommendations in Table 3 and current practice guidelines.1 Administer supportive care, which may include intensive care for severe or life-threatening cases.1

Patients who experienced any grade CRS during step-up dose 1 (2.5 mg) should be hospitalized during and for 24 hours after completion of step-up dose 2 (10 mg).1 For subsequent doses, patients who experienced Grade ≥2 CRS with the previous infusion should be hospitalized during and for 24 hours after the next glofitamab-gxbm infusion.1

Other Warnings/Precautions

Neurologic Toxicity, Including Immune Effector Cell-Associated Neurotoxicity Syndrome

Glofitamab-gxbm can cause serious and fatal neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS).1

In Study NP30179, of the 145 patients who received glofitamab-gxbm, the most frequent neurologic toxicities of any grade were headache (10%), peripheral neuropathy (8%), dizziness or vertigo (7%), and mental status changes, including confusional state, cognitive disorder, disorientation, somnolence, and delirium (4.8%).1 Grade ≥3 adverse events occurred in 2.1% of patients and included somnolence, delirium, and myelitis.1 ICANS of any grade occurred in 4.8% of patients.1

Concomitant administration of glofitamab-gxbm and other products that cause dizziness or mental status changes may increase the risk of neurologic toxicity.1 To minimize risk, optimize concomitant medications and hydration; institute fall precautions as appropriate.1

Monitor patients for signs and symptoms of neurologic toxicity.1 Evaluate patients who experience neurologic toxicity, including tremors, dizziness, or adverse reactions that may impair cognition or consciousness, and consider neurology evaluation.1 If neurologic toxicity is suspected, withhold or permanently discontinue glofitamab-gxbm based on severity; administer supportive care.1

Advise patients to refrain from driving and/or engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, until the neurologic toxicity fully resolves.1

Serious Infections

Glofitamab-gxbm can cause serious and fatal infections.1

In Study NP30179, serious infections of any grade were reported in 16% of patients, with Grade 3 or 4 infections occurring in 10% of patients and fatal infections occurring in 4.8% of patients.1 Grade ≥3 infections reported in ≥2% of patients were COVID-19 (6%), including COVID-19 pneumonia, and sepsis (4.1%).1 Febrile neutropenia occurred in 3.4% of patients.1

Patients with an active infection should not receive glofitamab-gxbm.1 Administer antimicrobial prophylaxis according to guidelines.1 Monitor patients before and during glofitamab-gxbm treatment for infection; treat appropriately.1 Withhold or consider permanent discontinuation of glofitamab-gxbm based on severity.1

Tumor Flare

Glofitamab-gxbm can cause serious tumor flare.1

In Study NP30179, tumor flare was reported in 12% of patients, with Grade 2 occurring in 4.8% of patients and Grade 3 occurring in 2.8% of patients.1 Two patients experienced recurrent tumor flare.1 The majority of tumor flare events occurred during Cycle 1.1 The median time to onset was 2 days (range: 1-16 days) following the first dose of glofitamab-gxbm.1 The median duration was 3.5 days (range: 1-35 days).1

Closely monitor patients with bulky tumors or disease located in close proximity to airways or a vital organ during initial therapy.1 Monitor for signs and symptoms of compression or obstruction due to mass effect secondary to tumor flare, and institute appropriate treatment.1 Withhold glofitamab-gxbm until tumor flare resolves.1

Fetal/Neonatal Morbidity and Mortality

Based on its mechanism of action, glofitamab-gxbm may cause fetal harm when administered to a pregnant woman.1

Advise pregnant women of the potential risk to the fetus.1 Advise females of reproductive potential to use effective contraception during treatment with glofitamab-gxbm and for 1 month after the last dose.1

Specific Populations

Pregnancy

There are no available data on glofitamab-gxbm use in pregnant women, and no animal reproductive or developmental toxicity studies have been conducted.1 However, based on its mechanism of action, glofitamab-gxbm may cause fetal harm when administered to a pregnant woman.1 The T-cell activation and cytokine release caused by glofitamab-gxbm may compromise pregnancy maintenance.1 Additionally, glofitamab-gxbm may cause B-cell lymphocytopenia in infants exposed in-utero.1 Human immunoglobulin (IgG) is known to cross the placenta; therefore, glofitamab-gxbm may potentially be transmitted from the mother to the developing fetus.1

Advise women of the potential risk to the fetus.1

Verify pregnancy status of females of reproductive potential prior to initiating glofitamab-gxbm.1

Females of reproductive potential and males with female partners of reproductive potential should use effective contraception during treatment with glofitamab-gxbm and for 1 month after the last dose.1

Lactation

It is not known whether glofitamab-gxbm is distributed into human milk.1 Effects of the drug on breastfed infants or milk production are also not known.1 However, because human IgG is present in human milk, and there is potential for glofitamab-gxbm absorption leading to B-cell depletion, advise women not to breastfeed during treatment and for 1 month after the last dose of glofitamab-gxbm.1

Females and Males of Reproductive Potential

Based on its mechanism of action, glofitamab-gxbm can cause embryo-fetal harm when administered to a pregnant woman.1

Verify pregnancy status prior to initiating treatment with glofitamab-gxbm.1

Females of reproductive potential and males with female partners of reproductive potential should use effective contraception during treatment with glofitamab-gxbm and for 1 month after the last dose.1

Pediatric Use

Safety and efficacy of glofitamab-gxbm have not been established in pediatric patients <18 years of age.1

Geriatric Use

In Study NP30179, 55% of the 145 glofitamab-gxbm-treated patients were ≥65 years of age and 23% were ≥75 years of age.1 Geriatric patients (≥65 years of age) experienced a higher rate of fatal adverse reactions, primarily from COVID-19, when compared to patients <65 years of age.1 No differences in efficacy were observed.1

Hepatic Impairment

Mild hepatic impairment (total bilirubin greater than ULN to ≤1.5 times ULN or AST greater than ULN) does not have a clinically important effect on the pharmacokinetics of glofitamab-gxbm; however, the effects of moderate-severe hepatic impairment (total bilirubin >1.5 times ULN and any AST) on the pharmacokinetics of the drug have not been studied.1

Renal Impairment

Mild-moderate renal impairment (creatinine clearance 30 to <90 mL/minute as estimated by Cockcroft-Gault formula) does not have a clinically important effect on the pharmacokinetics of glofitamab-gxbm; however the effects of severe renal impairment (creatinine clearance 15 to <30 mL/minute) or end-stage renal disease (creatinine clearance <15 mL/minute) on the pharmacokinetics of the drug have not been studied.1

Common Adverse Effects

The most common adverse reactions (incidence ≥20%) reported with glofitamab-gxbm in clinical studies were CRS, musculoskeletal pain, rash, and fatigue.1 The most common (incidence ≥20%) Grade 3 or 4 laboratory abnormalities reported with glofitamab-gxbm in clinical studies were decreased lymphocyte count, decreased phosphate, decreased neutrophil count, increased uric acid, and decreased fibrinogen.1

Glofitamab-gxbm is expected to be metabolized into small peptides by catabolic pathways.1

No clinical studies evaluating the drug interaction potential of glofitamab-gxbm have been conducted.1,  3

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Glofitamab-gxbm causes release of cytokines that may suppress the activity of CYP enzymes, resulting in increased exposure of cytochrome P450 (CYP) enzymes and increased exposure of CYP substrates.1 Increased exposure of CYP substrates is more likely to occur after the first dose of glofitamab-gxbm on Cycle 1 Day 8, up to 14 days after the first 30 mg dose on Cycle 2 Day 1, and during and after CRS.1 Monitor for toxicity or concentrations of drugs that are CYP substrates where minimal concentration changes may lead to serious adverse reactions.1

Description

Glofitamab-gxbm, a bispecific CD20-directed CD3 T-cell engager, is an antineoplastic agent.1 Glofitamab-gxbm binds to CD20 expressed on the surface of B cells and to CD3 receptor expressed on the surface of T cells, and causes T-cell activation and proliferation.1 In mouse models in DLBCL, glofitamab-gxbm demonstrated anti-tumor activity.1 Glofitamab-gxbm is manufactured in Chinese hamster ovary cells using recombinant DNA technology.1

Following administration of obinutuzumab 1000 mg pretreatment on Cycle 1 Day 1, peripheral B cell counts decreased to undetectable levels (<5 cells/microliter) in 86.5% of patients by Cycle 1 Day 7.1 By Cycle 1 Day 10, following administration of step-up dose 1 (2.5 mg) of glofitamab-gxbm, peripheral B cell counts decreased to undetectable levels (<5 cells/microliter) in 88.2% of patients.1 Transient elevation of circulating cytokines (interleukin [IL]-2, IL-6, IL-10, tumor necrosis factor-alpha, and interferon-gamma) was observed at dose levels of ≥0.045 mg.1 The highest cytokine levels were observed within 6 hours of administration of glofitamab-gxbm step-up dose 1 (2.5 mg) on Cycle 1 Day 8, and returned to baseline within 48 hours after the first 30 mg dose on Cycle 2 Day 1.1

Glofitamab-gxbm AUC increased proportionally over a full dosage range from 0.005 to 30 mg (0.000167 to 1 time the recommended treatment dosage).1 Peak plasma concentrations of glofitamab-gxbm are achieved approximately 4 hours following administration, near the end of the infusion.3 Steady state is achieved by approximately Cycle 6 (week 18).1 Glofitamab-gxbm is expected to be metabolized into small peptides by catabolic pathways.1 At steady state, the terminal half-life of glofitamab-gxbm is 7.6 days.1 Age (21-90 years), body weight (31-148 kg), sex, mild to moderate renal impairment (creatinine clearance 30 to <90 mL/minute as estimated by Cockcroft-Gault formula), and mild hepatic impairment (total bilirubin greater than ULN to ≤1.5 times ULN or AST greater than ULN) do not have clinically important effects on the pharmacokinetics of glofitamab-gxbm.1 The effects of severe renal impairment (creatinine clearance 15 to <30 mL/minute), end-stage renal disease (creatinine clearance <15 mL/minute), moderate to severe hepatic impairment (total bilirubin >1.5 times ULN and any AST), and race/ethnicity on the pharmacokinetics of glofitamab-gxbm are unknown.1

Advice to Patients

• Advise the patient to read the FDA-approved patient labeling.1
• Inform patients of the risk of cytokine release syndrome (CRS).1 Advise patients to seek immediate medical attention if they experience signs and symptoms of CRS (fever, hypoxia, hypotension, chills, and tachycardia).1
• Provide patients with the Patient Wallet Card that they should carry with them at all times.1 This card describes symptoms of CRS which, if experienced, should prompt the patient to seek immediate medical attention.1
• Discuss the signs and symptoms associated with neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), headache, peripheral neuropathy, dizziness, or mental status changes.1 Advise patients to immediately contact their healthcare provider if they experience any signs or symptoms of neurologic toxicity.1 Advise patients who experience neurologic toxicity that impairs consciousness to refrain from driving or operating heavy or potentially dangerous machinery until neurologic toxicity resolves.1
• Advise patients that glofitamab-gxbm can cause serious infections.1 Advise patients to notify their healthcare provider immediately if they develop any signs of infection (e.g., fever, chills, weakness).1
• Inform patients of the potential risk of tumor flare reaction and to report any signs and symptoms associated with this event (e.g., localized pain and swelling) to their healthcare provider for evaluation.1
• Advise pregnant women of the potential risk to a fetus.1 Advise females of reproductive potential to inform their healthcare provider if they are pregnant or become pregnant.1 Advise females of reproductive potential, and males with female partners of reproductive potential, to use effective contraception during treatment with glofitamab-gxbm and for 1 month after the last dose.1
• Advise women not to breastfeed while receiving treatment with glofitamab-gxbm and for 1 month after the last dose.1
• 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.1
• Inform patients of other important precautionary information.1

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. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].

Only references cited for selected revisions after 1984 are available electronically.

1. Genentech, Inc. COLUMVI^® (glofitamab-gxbm) injection prescribing information. South San Francisco, CA; 2025 June.

2. Dickinson MJ, Carlo-Stella C, Morschhauser F, et al. Glofitamab for relapsed or refractory diffuse large b-cell lymphoma. N Engl J Med. 2022;387(24):2220-2231.

3. US Food and Drug Administration. Center for Drug Evaluation and Research: Application number 761309. Multi-Discipline Review. 2023 June 15. From FDA website.

4. Zelenetz AD, Gordon LI, Abramson JS, et al. NCCN Guidelines^® Insights: B-Cell Lymphomas, Version 6.2023. J Natl Compr Canc Netw. 2023;21(11):1118-1131.

5. Helpful Resources for Your Practice. COLUMVI^® (glofitamab-gxbm). Accessed September 29, 2025. [Web]