Glofitamab

Glofitamab is a prescription medication indicated for the treatment of 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 or more lines of systemic therapy

• Glofitamab is available under the following different brand names: glofitamab-gxbm, Columvi.

Common side effects of Glofitamab include:

• cytokine release syndrome
• musculoskeletal pain
• rash
• fatigue
• decreased white blood cells (lymphocytes, neutrophils)
• decreased phosphate
• increased uric acid
• decreased fibrinogen

Serious side effects of Glofitamab include:

• cytokine release syndrome
• neurologic problems includes-headache, confusion, disorientation, difficulty paying attention or understanding things, trouble speaking, sleepiness, memory problems, numbness, tingling, or weakness of the hands or feet, dizziness, and shaking (tremors)
• serious infections include- fever, chills, weakness, cough, shortness of breath, or sore throat. 
• growth in your tumor or worsening of tumor-related problems (tumor flare) includes- tender or swollen lymph nodes, pain or swelling at the site of the tumor, chest pain, cough, and trouble breathing

Rare side effects of Glofitamab include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Injectable solution

• 1 mg/mL (2.5-mL, 10-mL single-dose vials)

B-cell lymphoma

Adult dosage

• Step-up dose schedule
• Dosing begins with a step-up dose schedule
• Administer premedications (ie, dexamethasone, acetaminophen, diphenhydramine) for each dose.
• Cycle 1
  • Day 1: Obinutuzumab 1000 mg IV ×1 dose, 7 days before initiating Glofitamab to deplete circulating and lymphoid tissue B cells
  • Day 8 (step-up dose 1): 2.5 mg IV over 4 hours × 1
  • Day 15 (step-up dose 2): 10 mg IV over 4 hours × 1
  • If cytokine release syndrome (CRS) occurs, extend the infusion rate of the subsequent dose up to 8 hours
• Cycle 2
  • Day 1: 30 mg IV over 4 hours
  • If CRS is experienced with a previous dose, extend the infusion rate up to 8 hours
• Cycle 3-12
  • Day 1: 30 mg IV over 2 hours
  • If CRS is experienced with the previous dose, maintain the duration of infusion at 4 hours
  • Continue for a maximum of 12 cycles (inclusive of Cycle 1 step-up dosing) or until disease progression or unacceptable toxicity, whichever occurs first

Dosage Considerations – Should be Given as Follows:

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Glofitamab has no noted severe interactions with any other drugs.
• Glofitamab has no noted serious interactions with any other drugs.
• Glofitamab has no noted moderate interactions with any other drugs.
• Glofitamab has no noted minor interactions with any other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Glofitamab?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Glofitamab?”

Cautions

• Serious or fatal infections reported; administer antimicrobial prophylaxis according to guidelines; do not administer to patients with active infection; monitor patients before and during treatment for infection and treat them appropriately
• Based on its mechanism of action, fetal harm may occur when administered to pregnant women
• Tumor flares
  • May cause serious tumor flare; symptoms include localized pain and swelling at the sites of the lymphoma lesions and/or dyspnea from new pleural effusions
  • Closely monitor patients with bulky tumors or diseases located near airways or a vital organ during initial therapy
  • Monitor for signs and symptoms of compression or obstruction owing to mass effect secondary to tumor flare and institute appropriate treatment
  • Withhold therapy until tumor flare resolves
• Neurologic toxicity
  • May cause serious and fatal neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS)
  • Coadministration with other products that cause dizziness or mental status changes may increase the risk for neurologic toxicity
  • Optimize concomitant medications and hydration to avoid dizziness or mental status changes
  • Institute fall precautions as appropriate
  • Monitor for signs and symptoms of neurologic toxicity, evaluate and provide supportive therapy; withhold or permanently discontinue therapy based on the severity of neurotoxicity
  • Promptly evaluate patients who experience neurologic toxicity such as tremors, dizziness, or adverse reactions that may impair cognition or consciousness; consider neurological evaluation
  • Advise affected patients to refrain from driving and/or engaging in hazardous occupations or activities (e.g., operating heavy or potentially dangerous machinery) until neurologic toxicity fully resolves
• Cytokine release syndrome
  • May cause serious and fatal CRS
  • Most common manifestations of CRS included fever, tachycardia, hypotension, chills, and hypoxia
  • Administer Glofitamab in a facility equipped to monitor and manage CRS
• Drug interactions overview
  • Sensitive CYP substrates
  • Monitor for toxicities or drug concentrations of sensitive CYP substrates
  • Glofitamab causes a release of cytokines that may suppress the activity of CYP enzymes, resulting in increased exposure to CYP substrates
  • Increased exposure of CYP substrates is more likely to occur after the first dose of Glofitamab (Cycle 1 Day 8), up to 14 days after the first 30-mg dose (Cycle 2 Day 1), and during and after CRS

Pregnancy and Lactation

• Based on its mechanism of action, fetal harm may occur when administered to pregnant women. No data are available on use in pregnant women to evaluate for a drug-associated risk
• No animal reproductive and developmental toxicity studies have been conducted
• Glofitamab causes T-cell activation and cytokine release; immune activation may compromise pregnancy maintenance; human immunoglobulin G (IgG) is known to cross the placenta; therefore, glofitamab has the potential to be transmitted from the mother to the developing fetus
• Advise women of the potential risk to a fetus
• Verify pregnancy status in women of reproductive potential before initiating
• Contraception
  • Females of reproductive potential: Use effective contraception during treatment and for 1 month after the last dose
• Lactation
  • There are no data on the presence of glofitamab in human milk or its effects on breastfed children or milk production
  • Advise women not to breastfeed during treatment and for 1 month after the last dose