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Columvi Dosage

Drug Detail:Columvi (Glofitamab-gxbm)

Generic Name: Medically reviewed

Drug Class:

Contents
Uses Warnings Before Taking Dosage Side effects Interactions

Important Dosing Information

  • Administer only as an intravenous infusion through a dedicated infusion line that includes a sterile 0.2-micron in-line filter.
  • COLUMVI should only be administered by a healthcare professional with immediate access to appropriate medical support, including supportive medications to manage severe CRS [see Dosage and Administration (2.4)].
  • Ensure adequate hydration before administering COLUMVI.
  • Premedicate before each dose [see Dosage and Administration (2.3)].
  • Following pretreatment with obinutuzumab, administer COLUMVI according to the step-up dosing schedule in Table 1 with appropriate premedication, including dexamethasone, to reduce the incidence and severity of CRS [see Dosage and Administration (2.3)].
  • Due to the risk of CRS, patients should be hospitalized during and for 24 hours after completion of infusion of step-up dose 1 (2.5 mg on Cycle 1 Day 8) [see Dosage and Administration (2.2) and Warnings and Precautions (5.1)].
  • Patients who experienced any grade CRS during step-up dose 1 should be hospitalized 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 [see Dosage and Administration (2.2) and Warnings and Precautions (5.1)].
  • For subsequent doses, patients who experienced Grade ≥ 2 CRS with their previous infusion should be hospitalized during and for 24 hours after the completion of the next COLUMVI infusion.

Recommended Dosage

Pretreatment with Obinutuzumab

Pretreat all patients with a single 1,000 mg dose of obinutuzumab administered as an intravenous infusion on Cycle 1 Day 1, 7 days prior to initiation of COLUMVI (see Table 1) to deplete the circulating and lymphoid tissue B cells.

Obinutuzumab should be administered as an intravenous infusion at 50 mg/hour. The rate of infusion can be escalated 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.

COLUMVI Step-up Dose Schedule

COLUMVI dosing begins with a step-up dose schedule. Following completion of pretreatment with obinutuzumab on Cycle 1 Day 1, administer COLUMVI as an intravenous infusion according to the step-up dose schedule in Table 1. Administer premedications for each dose of COLUMVI as described in Table 3 [see Dosage and Administration (2.3)].

Table 1: COLUMVI Dosing Schedule (21-Day Treatment Cycles)
Treatment cycle Day Dose of COLUMVI Duration of infusion
*
Refer to "Pretreatment with obinutuzumab" described above.
†
For patients who experience CRS with their previous dose of COLUMVI, the time of infusion may be extended up to 8 hours.
‡
If the patient experienced CRS with the previous dose, the duration of infusion should be maintained at 4 hours.
Cycle 1 Day 1 Obinutuzumab*
Day 8 Step-up dose 1 2.5 mg 4 hours†
Day 15 Step-up dose 2 10 mg
Cycle 2 Day 1 30 mg 4 hours†
Cycle 3 to 12 Day 1 30 mg 2 hours‡

Continue COLUMVI for a maximum of 12 cycles (inclusive of Cycle 1 step-up dosing) or until disease progression or unacceptable toxicity, whichever occurs first.

Monitoring for Cytokine Release Syndrome [see Warnings and Precautions (5.1)]

  • Administer the COLUMVI infusions intravenously in a healthcare setting with immediate access to medical support to manage CRS, including severe CRS.
  • For the first COLUMVI step-up dose (2.5 mg on Cycle 1 Day 8), patients should be hospitalized during and for 24 hours after completion of the COLUMVI infusion.
  • Patients who experienced any grade CRS during step-up dose 1 should be hospitalized 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.
  • For subsequent infusions (30 mg on Day 1 of Cycle 2 or subsequent cycles), patients who experienced Grade ≥ 2 CRS with their previous infusion should be hospitalized during and for 24 hours after completion of the next COLUMVI infusion.
  • For monitoring after delayed or missed doses of COLUMVI, follow the recommendations in Table 2.

Delayed or Missed Doses

If a dose of COLUMVI is delayed, restart therapy based on the recommendations made in Table 2, then resume the treatment schedule accordingly.

For repeat of the 2.5 mg dose patients should be hospitalized during and for 24 hours after completion of the COLUMVI infusion. For the repeat of the 10 mg dose, patients should be hospitalized during and for 24 hours after completion of the COLUMVI infusion if any grade CRS occurred during the most recent 2.5 mg dose.

Table 2: Recommendations for Restarting COLUMVI After Dose Delay
Last Dose Administered Time Since Last Dose Administered Action for Next Dose(s)*
*
Administer premedication as per Table 3 for all patients.
†
Patients should be hospitalized during and for 24 hours after completing infusion of the 2.5 mg dose.
‡
Patients should be hospitalized during and for 24 hours after completing infusion of the 10 mg dose if CRS occurred during the most recent 2.5 mg dose.
Obinutuzumab pretreatment (Cycle 1 Day 1) ≤ 2 weeks
  • Administer COLUMVI 2.5 mg (Cycle 1 Day 8)†, then resume the planned treatment schedule.
> 2 weeks
  • Repeat obinutuzumab 1,000 mg pretreatment (Cycle 1 Day 1).
  • Then administer COLUMVI 2.5 mg (Cycle 1 Day 8)† and resume the planned treatment schedule.
COLUMVI 2.5 mg
(Cycle 1 Day 8)		 ≤ 2 weeks
  • Administer COLUMVI 10 mg (Cycle 1 Day 15)‡, then resume the planned treatment schedule.
> 2 to ≤ 4 weeks
  • Repeat COLUMVI 2.5 mg (Cycle 1 Day 8)†.
  • Then administer COLUMVI 10 mg (Cycle 1 Day 15)‡ and resume the planned treatment schedule.
> 4 weeks
  • Repeat obinutuzumab 1,000 mg pretreatment (Cycle 1 Day 1) and COLUMVI 2.5 mg (Cycle 1 Day 8)†.
  • Then administer COLUMVI 10 mg (Cycle 1 Day 15)‡ and resume the planned treatment schedule.
COLUMVI 10 mg
(Cycle 1 Day 15)		 ≤ 2 weeks
  • Administer COLUMVI 30 mg (Cycle 2 Day 1), then resume the planned treatment schedule.
> 2 to ≤ 6 weeks
  • Repeat COLUMVI 10 mg (Cycle 1 Day 15).‡
  • Then administer COLUMVI 30 mg (Cycle 2 Day 1) and resume the planned treatment schedule.
> 6 weeks
  • Repeat obinutuzumab 1,000 mg pretreatment (Cycle 1 Day 1), COLUMVI 2.5 mg (Cycle 1 Day 8)†, and COLUMVI 10 mg (Cycle 1 Day 15)‡.
  • Then administer COLUMVI 30 mg (Cycle 2 Day 1) and resume the planned treatment schedule.
COLUMVI 30 mg
(Cycle 2 onwards)		 ≤ 6 weeks
  • Administer COLUMVI 30 mg, then resume the planned treatment schedule.
> 6 weeks
  • Repeat the Cycle 1 regimen described in Table 1: obinutuzumab 1,000 mg pretreatment (Day 1), COLUMVI 2.5 mg (Day 8)†, and COLUMVI 10 mg (Day 15)‡.
  • Then administer COLUMVI 30 mg (Day 1 of next cycle) and resume the planned treatment schedule.

Recommended Premedication and Prophylactic Medications

Premedication

Administer the following premedications to reduce the risk of CRS and infusion-related reactions [see Warnings and Precautions (5.1)].

Table 3: Premedications to be Administered for COLUMVI Infusion
Day of Treatment Cycle Patients requiring premedication Premedication Administration
*
If dexamethasone is not available, administer prednisone 100 mg, prednisolone 100 mg, or methylprednisolone 80 mg intravenously.
Cycle 1, Day 8 and Day 15; Cycle 2; Cycle 3 Dexamethasone 20 mg intravenously* Completed at least 1 hour prior to COLUMVI infusion.
All patients Acetaminophen 500 mg to 1,000 mg orally At least 30 minutes before COLUMVI infusion.
Antihistamine (diphenhydramine 50 mg orally or intravenously or equivalent) Completed at least 30 minutes before COLUMVI infusion.
All subsequent infusions All patients Acetaminophen 500 mg to 1,000 mg orally At least 30 minutes before COLUMVI infusion.
Antihistamine (diphenhydramine 50 mg orally or intravenously or equivalent) Completed at least 30 minutes before COLUMVI infusion.
Patients who experienced any grade CRS with the previous dose Dexamethasone 20 mg intravenously* Completed at least 1 hour prior to COLUMVI infusion.

Tumor Lysis Syndrome Prophylaxis

Before starting COLUMVI, administer anti-hyperuricemics to patients at risk of tumor lysis syndrome, ensure adequate hydration status, and monitor as appropriate [see Adverse Reactions (6.1)].

Antiviral Prophylaxis

Before starting COLUMVI, consider initiation of antiviral prophylaxis to prevent herpes virus reactivation. Consider prophylaxis for cytomegalovirus infection in patients at increased risk [see Warnings and Precautions (5.3)].

Pneumocystis jirovecii Pneumonia (PJP)

Consider PJP prophylaxis prior to starting COLUMVI in patients at increased risk [see Warnings and Precautions (5.3)].

Dosage Modifications for Adverse Reactions

No dosage reduction for COLUMVI is recommended.

Cytokine Release Syndrome

Identify CRS based on clinical presentation [see Warnings and Precautions (5.1)]. Evaluate for and treat other causes of fever, hypoxia, and hypotension.

If CRS is suspected, withhold COLUMVI and manage according to the recommendations in Table 4 and current practice guidelines. Administer supportive care for CRS, which may include intensive care for severe or life-threatening cases.

Table 4: Recommendations for Management of Cytokine Release Syndrome
Grade* Presenting Symptoms Actions
*
American Society for Transplantation and Cellular Therapy (ASTCT) 2019 consensus grading criteria.
†
Premedication may mask fever. Therefore if clinical presentation is consistent with CRS, follow these management guidelines.
‡
Duration of infusion may be extended up to 8 hours, as appropriate for that cycle (see Table 1).
§
Refer to Table 2 for information on restarting COLUMVI after dose delays [see Dosage and Administration (2.2)].
Low-flow oxygen defined as oxygen delivered at < 6 L/minute, high-flow oxygen defined as oxygen delivered at ≥ 6 L/minute.
Grade 1 Temperature ≥ 100.4°F (38°C)†
  • Withhold COLUMVI and manage per current practice guidelines.
    • If symptoms resolve, restart infusion at a slower rate.‡
  • Ensure CRS symptoms are resolved for at least 72 hours before next dose.§
  • Consider slower infusion rate for next dose.
Grade 2 Temperature ≥ 100.4°F (38°C)† with:
Hypotension not requiring vasopressors
and/or
Hypoxia requiring low-flow oxygen¶ by nasal cannula or blow-by
  • Withhold COLUMVI and manage per current practice guidelines.
    • If symptoms resolve, restart infusion at a slower rate.‡
  • Ensure CRS symptoms are resolved for at least 72 hours before next dose.§
  • 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 ≥ 100.4°F (38°C)† 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 COLUMVI and manage per current practice guidelines, which may include intensive care.
  • Ensure CRS symptoms are resolved for at least 72 hours before next dose.§
  • Hospitalize for the next dose, monitor more frequently, and consider a slower infusion rate.‡
  • For recurrent Grade 3 CRS, permanently discontinue COLUMVI.
Grade 4 Temperature ≥ 100.4°F (38°C)† with:
Hypotension requiring multiple vasopressors (excluding vasopressin)
and/or
Hypoxia requiring oxygen by positive pressure (e.g., CPAP, BiPAP, intubation, and mechanical ventilation)
  • Permanently discontinue COLUMVI and manage per current practice guidelines, which may include intensive care.

Neurologic Toxicity, Including ICANS

Management recommendations for neurologic toxicity, including ICANS, is summarized in Table 5. At the first sign of neurologic toxicity, including ICANS, consider neurology evaluation and withholding COLUMVI based on the type and severity of neurotoxicity. Rule out other causes of neurologic symptoms. Provide supportive therapy, which may include intensive care.

Table 5: Recommended Dosage Modification for Neurologic Toxicity (Including ICANS)
Adverse Reaction Severity*,† Actions
*
Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03.
†
Based on ASTCT 2019 grading for ICANS.
‡
Consider the type of neurologic toxicity before deciding to withhold COLUMVI.
§
See Dosage and Administration (2.2) on restarting COLUMVI after dose delays.
Evaluate benefit-risk before restarting COLUMVI.
Grade 1
  • Continue COLUMVI and monitor neurologic toxicity symptoms.
  • If ICANS, manage per current practice guidelines.
Grade 2
  • Withhold COLUMVI until neurologic toxicity symptoms improve to Grade 1 or baseline.‡, §
  • Provide supportive therapy, and consider neurologic evaluation.
  • If ICANS, manage per current practice guidelines.
Neurologic Toxicity* (including ICANS†) [see Warnings and Precautions (5.2)] Grade 3
  • Withhold COLUMVI until neurologic toxicity symptoms improve to Grade 1 or baseline for at least 7 days.§,
  • For Grade 3 neurologic events lasting more than 7 days, consider permanently discontinuing COLUMVI.
  • Provide supportive therapy, and consider neurology evaluation.
  • If ICANS, manage per current practice guidelines.
Grade 4
  • Permanently discontinue COLUMVI.
  • Provide supportive therapy, which may include intensive care, and consider neurology evaluation.
  • If ICANS, manage per current practice guidelines.

Other Adverse Reactions

Table 6: Recommended Dosage Modifications for Other Adverse Reactions
Adverse Reactions* Severity* Actions
*
Based on NCI CTCAE, version 4.03.
†
See Dosage and Administration (2.2) on restarting COLUMVI after dose delays.
Infections [see Warnings and Precautions (5.3)] Grades 1 – 4
  • Withhold COLUMVI in patients with active infection until the infection resolves.†
  • For Grade 4, consider permanent discontinuation of COLUMVI.
Grade 1
  • Monitor for signs and symptoms of compression or obstruction due to mass effect secondary to tumor flare.
Tumor flare [see Warnings and Precautions (5.4)] 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 COLUMVI until tumor flare resolves.†
Neutropenia Absolute neutrophil count less than 0.5 × 109/L
  • Withhold COLUMVI until absolute neutrophil count is 0.5 × 109/L or higher.†
Thrombocytopenia Platelet count less than 50 × 109/L
  • Withhold COLUMVI until platelet count is 50 × 109/L or higher.†
Other Adverse Reactions [see Adverse Reactions (6.1)] Grade 3 or higher
  • Withhold COLUMVI until the toxicity resolves to Grade 1 or baseline.†

Preparation and Administration

Preparation

  • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. COLUMVI is a colorless clear solution. Discard the vial if the solution is cloudy, discolored, or contains visible particles.
  • Use aseptic technique when preparing the COLUMVI diluted solution for intravenous infusion.
  • Determine the dose, total volume of COLUMVI solution, and the number of COLUMVI vials needed (see Table 7).

Dilution

  • Withdraw the volume of 0.9% Sodium Chloride Injection or 0.45% Sodium Chloride Injection from the infusion bag according to Table 7 and discard.
  • Withdraw the required volume of COLUMVI from vial(s) using a sterile needle and syringe and dilute into the infusion bag of 0.9% Sodium Chloride Injection or 0.45% Sodium Chloride Injection according to Table 7 to a final concentration of 0.1 mg/mL to 0.6 mg/mL. Discard any unused portion left in the vial.
Table 7: Dilution of COLUMVI for infusion
Dose of COLUMVI Size of infusion bag Volume of 0.9% Sodium Chloride Injection or 0.45% Sodium Chloride Injection to be withdrawn and discarded Volume of COLUMVI to be added in the infusion bag
2.5 mg 50 mL 27.5 mL 2.5 mL
10 mg 50 mL 10 mL 10 mL
100 mL 10 mL 10 mL
30 mg 50 mL 30 mL 30 mL
100 mL 30 mL 30 mL
  • Gently invert infusion bag to mix the solution, in order to avoid excessive foaming. Do not shake.
  • Immediately use diluted COLUMVI solution. If not used immediately, the diluted solution can be stored:
    • Refrigerated at 2°C to 8°C (36°F to 46°F) for up to 64 hours, or
    • At room temperature up to 25°C (77°F) for up to 4 hours.
    • Do not freeze the diluted infusion solution.
    • Discard diluted infusion solution if storage time exceeds these limits.

COLUMVI diluted with 0.9% Sodium Chloride Injection is compatible with intravenous infusion bags composed of polyvinyl chloride (PVC), polyethylene (PE), polypropylene (PP) or non-PVC polyolefin. When diluted with 0.45% Sodium Chloride Injection, COLUMVI is compatible with intravenous infusion bags composed of PVC.

No incompatibilities have been observed with infusion sets with product-contacting surfaces of polyurethane (PUR), PVC, or PE, and in-line filter membranes composed of polyethersulfone (PES) or polysulfone.

COLUMVI Administration

  • Administer COLUMVI as an intravenous infusion only through a dedicated infusion line that includes a sterile 0.2-micron in-line filter.
  • See Table 1 for duration of infusion. The maximum time for the administration of the diluted infusion solution may be extended up to 8 hours (see Table 4).
  • Do not mix COLUMVI with other drugs.
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