Columvi

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)].

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.

Premedication

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

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)].

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.

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.

Other Adverse Reactions

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.

• 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.

Risk Summary

Based on its mechanism of action COLUMVI may cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)]. There are no available data on the use of COLUMVI in pregnant women to evaluate for a drug-associated risk. No animal reproductive and developmental toxicity studies have been conducted with glofitamab-gxbm.

Glofitamab-gxbm causes T-cell activation and cytokine release; immune activation may compromise pregnancy maintenance. In addition, based on expression of CD20 on B cells and the finding of B-cell depletion in non-pregnant animals, glofitamab-gxbm can cause B-cell lymphocytopenia in infants exposed to glofitamab-gxbm in-utero. Human immunoglobulin G (IgG) is known to cross the placenta; therefore, COLUMVI has the potential to be transmitted from the mother to the developing fetus. Advise women of the potential risk to the fetus.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Risk Summary

There are no data on the presence of glofitamab-gxbm in human milk or the effects on the breastfed child or milk production. 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 with COLUMVI and for 1 month after the last dose of COLUMVI.

Pregnancy Testing

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

Contraception