Glofitamab-gxbm: Difference between revisions
(Created page with "{{DrugProjectFormSinglePage |authorTag=Muhammad Waleed, M.B.B.S. [mailto:muhammad_waleed@ymail.com] |genericName=glofitamab. |aOrAn=a |drugClass=bispecific antibodies |indicationType=treatment |indication=COLUMVI (glofitamab) has been approved by the FDA for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), or large B-cell lymphoma arising from follicular lymphoma aft...") |
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|blackBoxWarningBody=Cytokine Release Syndrome (CRS), including serious or fatal reactions, can occur in patients receiving COLUMVI. Premedicate before each dose, and initiate treatment with the COLUMVI step-up dosing schedule to reduce the risk of CRS. Withhold COLUMVI until CRS resolves or permanently discontinue based on severity. | |blackBoxWarningBody=Cytokine Release Syndrome (CRS), including serious or fatal reactions, can occur in patients receiving COLUMVI. Premedicate before each dose, and initiate treatment with the COLUMVI step-up dosing schedule to reduce the risk of CRS. Withhold COLUMVI until CRS resolves or permanently discontinue based on severity. | ||
|fdaLIADAdult=COLUMVI (glofitamab) is administered intravenously and requires careful dosage and administration protocols. It begins with pretreatment using a single 1,000 mg dose of obinutuzumab administered intravenously 7 days before initiating COLUMVI. The administration of COLUMVI itself follows a step-up dosing schedule to mitigate the risk of Cytokine Release Syndrome (CRS). The initial step-up dose on Cycle 1 Day 8 is 2.5 mg, followed by a 10 mg dose on Day 15. From Cycle 2 to Cycle 12, a 30 mg dose is administered on Day 1 of each 21-day cycle. Due to the risk of CRS, patients must be hospitalized for the 2.5 mg step-up dose and closely monitored for subsequent doses, especially after experiencing any grade of CRS during prior administrations. Each infusion should only be conducted in a facility equipped to manage severe adverse reactions, ensuring the safety and well-being of the patient. | |fdaLIADAdult=COLUMVI (glofitamab) is administered intravenously and requires careful dosage and administration protocols. It begins with pretreatment using a single 1,000 mg dose of obinutuzumab administered intravenously 7 days before initiating COLUMVI. The administration of COLUMVI itself follows a step-up dosing schedule to mitigate the risk of Cytokine Release Syndrome (CRS). The initial step-up dose on Cycle 1 Day 8 is 2.5 mg, followed by a 10 mg dose on Day 15. From Cycle 2 to Cycle 12, a 30 mg dose is administered on Day 1 of each 21-day cycle. Due to the risk of CRS, patients must be hospitalized for the 2.5 mg step-up dose and closely monitored for subsequent doses, especially after experiencing any grade of CRS during prior administrations. Each infusion should only be conducted in a facility equipped to manage severe adverse reactions, ensuring the safety and well-being of the patient. | ||
|clinicalTrials=During the clinical trials of COLUMVI (glofitamab), a range of adverse reactions were observed, some of which were serious or severe. The most commonly reported adverse reaction was Cytokine Release Syndrome (CRS), affecting a significant proportion of patients, with varying degrees of severity including serious or fatal cases. Other common adverse reactions included musculoskeletal pain, which covered discomfort in muscles, bones, back, neck, and extremities. Skin reactions were also frequent, encompassing different types of rashes such as dermatitis and erythema. Additionally, fatigue was a prevalent issue, significantly impacting patient well-being. Neurological toxicities were also reported, including severe outcomes such as Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS). The trials noted instances of serious infections, some of which were fatal. Given the intensity and potential severity of these reactions, meticulous monitoring and management protocols were essential during the administration of COLUMVI in the trials. | |||
|useInLaborDelivery=Based on its mechanism of action, COLUMVI may cause fetal harm when administered to a pregnant woman. The drug causes T-cell activation and cytokine release, which can compromise pregnancy maintenance. Furthermore, due to the expression of CD20 on B cells and the potential for B-cell depletion observed in non-pregnant animals, glofitamab can lead to B-cell lymphocytopenia in infants exposed to the drug in utero. Human immunoglobulin G (IgG) is known to cross the placenta, and hence, COLUMVI has the potential to be transmitted from the mother to the developing fetus. 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 | |||
|administration=COLUMVI (glofitamab) is administered intravenously and involves a detailed preparation and dosing schedule to mitigate the risk of Cytokine Release Syndrome (CRS). The administration begins with pretreatment using a single 1,000 mg dose of obinutuzumab, given intravenously seven days prior to starting COLUMVI. The step-up dosing schedule of COLUMVI starts on Cycle 1 Day 8 with a 2.5 mg dose administered over four hours, followed by a 10 mg dose on Cycle 1 Day 15, also over four hours. From Cycle 2 to Cycle 12, a 30 mg dose is administered on Day 1 of each 21-day cycle over two hours. The preparation of COLUMVI involves using aseptic techniques, inspecting the solution for particulate matter and discoloration, and diluting it appropriately in an infusion bag. The infusion bag should be gently inverted to mix the solution without shaking, and the diluted solution should be used immediately or stored under specified conditions if not used right away. | |||
|monitoring=Monitoring during and after the administration of COLUMVI is crucial to ensure patient safety and manage potential adverse reactions. Patients must be adequately hydrated before administration and premedicated to reduce the risk of CRS and infusion-related reactions. The infusion should be conducted in a healthcare setting equipped to manage severe adverse reactions. During the infusion, patients should be monitored closely for signs of CRS, such as fever, chills, hypotension, and hypoxia, and for at least 24 hours after completion of the 2.5 mg and 10 mg step-up doses. Subsequent doses require hospitalization and close observation, especially for patients who experienced CRS with previous doses. Regular clinical evaluations are necessary to assess the efficacy and safety of the treatment, and any adverse reactions should be managed according to current guidelines. | |||
|IVCompat=Yes, COLUMVI (glofitamab) is compatible with intravenous (IV) administration. The preparation involves diluting the required volume of COLUMVI into an infusion bag containing 0.9% Sodium Chloride Injection or 0.45% Sodium Chloride Injection to a final concentration of 0.1 mg/mL to 0.6 mg/mL. | |||
|mechAction=COLUMVI (glofitamab) is a bispecific CD20-directed CD3 T-cell engager designed to target and eliminate B-cell malignancies. Its mechanism of action involves binding to CD20, a protein expressed on the surface of B-cells, and CD3, a component of the T-cell receptor complex on T-cells. By engaging both targets simultaneously, COLUMVI brings T-cells into close proximity with B-cells, thereby facilitating T-cell activation and subsequent B-cell lysis. This targeted approach leverages the body’s immune system to specifically attack and destroy cancerous B-cells while minimizing damage to other cells. | |||
|PD=The pharmacodynamics of COLUMVI are centered around its ability to induce T-cell mediated cytotoxicity against CD20-expressing B-cells. Upon administration, glofitamab binds to CD20 on malignant B-cells and CD3 on T-cells, resulting in T-cell activation, proliferation, and targeted killing of B-cells. This engagement leads to the release of cytokines, which further enhance the immune response against the tumor. The reduction in B-cell numbers, including malignant cells, is associated with clinical improvements in patients with B-cell lymphomas. The pharmacodynamic effects are closely monitored to manage potential adverse reactions such as Cytokine Release Syndrome (CRS), which is indicative of the drug’s potent immunological activity. | |||
|PK=The pharmacokinetics of COLUMVI involve its absorption, distribution, metabolism, and excretion. Following intravenous administration, glofitamab exhibits a multi-phase pharmacokinetic profile. The drug shows a rapid initial distribution phase followed by a slower elimination phase. The apparent volume of distribution is relatively small, indicating limited distribution beyond the vascular and interstitial compartments. Glofitamab is not metabolized by cytochrome P450 enzymes but is instead degraded into small peptides and amino acids through proteolytic pathways typical for monoclonal antibodies. The clearance of glofitamab is mediated through cellular catabolism, with a half-life that supports its dosing schedule of every three weeks after the initial step-up doses. | |||
}} | }} | ||
Latest revision as of 14:51, 23 May 2024
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Muhammad Waleed, M.B.B.S. [2]
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Black Box Warning
|
CYTOKINE RELEASE SYNDROME
See full prescribing information for complete Boxed Warning.
Cytokine Release Syndrome (CRS), including serious or fatal reactions, can occur in patients receiving COLUMVI. Premedicate before each dose, and initiate treatment with the COLUMVI step-up dosing schedule to reduce the risk of CRS. Withhold COLUMVI until CRS resolves or permanently discontinue based on severity.
|
Overview
Glofitamab-gxbm is a bispecific antibodies that is FDA approved for the treatment of COLUMVI (glofitamab) has been approved by the FDA for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), or large B-cell lymphoma arising from follicular lymphoma after at least two prior lines of systemic therapy. This approval is granted under the FDA’s accelerated approval program based on the tumor response rate and durability of the response observed in clinical trials. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.. There is a Black Box Warning for this drug as shown here. Common adverse reactions include 1. Cytokine Release Syndrome (CRS): Occurs in the majority of patients, with symptoms that can range from mild to severe, including fever, chills, hypotension, and hypoxia. 2. Musculoskeletal Pain: Includes pain in muscles, bones, back, neck, and extremities. 3. Rash: Various types of skin reactions, which can include general rashes, dermatitis, and erythema. 4. Fatigue: A significant number of patients report feeling unusually tired or weak..
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
COLUMVI (glofitamab) is administered intravenously and requires careful dosage and administration protocols. It begins with pretreatment using a single 1,000 mg dose of obinutuzumab administered intravenously 7 days before initiating COLUMVI. The administration of COLUMVI itself follows a step-up dosing schedule to mitigate the risk of Cytokine Release Syndrome (CRS). The initial step-up dose on Cycle 1 Day 8 is 2.5 mg, followed by a 10 mg dose on Day 15. From Cycle 2 to Cycle 12, a 30 mg dose is administered on Day 1 of each 21-day cycle. Due to the risk of CRS, patients must be hospitalized for the 2.5 mg step-up dose and closely monitored for subsequent doses, especially after experiencing any grade of CRS during prior administrations. Each infusion should only be conducted in a facility equipped to manage severe adverse reactions, ensuring the safety and well-being of the patient.
Off-Label Use and Dosage (Adult)
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Glofitamab-gxbm FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Contraindications
There is limited information regarding Glofitamab-gxbm Contraindications in the drug label.
Warnings
|
CYTOKINE RELEASE SYNDROME
See full prescribing information for complete Boxed Warning.
Cytokine Release Syndrome (CRS), including serious or fatal reactions, can occur in patients receiving COLUMVI. Premedicate before each dose, and initiate treatment with the COLUMVI step-up dosing schedule to reduce the risk of CRS. Withhold COLUMVI until CRS resolves or permanently discontinue based on severity.
|
There is limited information regarding Glofitamab-gxbm Warnings' in the drug label.
Adverse Reactions
Clinical Trials Experience
During the clinical trials of COLUMVI (glofitamab), a range of adverse reactions were observed, some of which were serious or severe. The most commonly reported adverse reaction was Cytokine Release Syndrome (CRS), affecting a significant proportion of patients, with varying degrees of severity including serious or fatal cases. Other common adverse reactions included musculoskeletal pain, which covered discomfort in muscles, bones, back, neck, and extremities. Skin reactions were also frequent, encompassing different types of rashes such as dermatitis and erythema. Additionally, fatigue was a prevalent issue, significantly impacting patient well-being. Neurological toxicities were also reported, including severe outcomes such as Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS). The trials noted instances of serious infections, some of which were fatal. Given the intensity and potential severity of these reactions, meticulous monitoring and management protocols were essential during the administration of COLUMVI in the trials.
Postmarketing Experience
There is limited information regarding Glofitamab-gxbm Postmarketing Experience in the drug label.
Drug Interactions
There is limited information regarding Glofitamab-gxbm Drug Interactions in the drug label.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Glofitamab-gxbm in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Glofitamab-gxbm in women who are pregnant.
Labor and Delivery
Based on its mechanism of action, COLUMVI may cause fetal harm when administered to a pregnant woman. The drug causes T-cell activation and cytokine release, which can compromise pregnancy maintenance. Furthermore, due to the expression of CD20 on B cells and the potential for B-cell depletion observed in non-pregnant animals, glofitamab can lead to B-cell lymphocytopenia in infants exposed to the drug in utero. Human immunoglobulin G (IgG) is known to cross the placenta, and hence, COLUMVI has the potential to be transmitted from the mother to the developing fetus. 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
Nursing Mothers
There is no FDA guidance on the use of Glofitamab-gxbm in women who are nursing.
Pediatric Use
There is no FDA guidance on the use of Glofitamab-gxbm in pediatric settings.
Geriatic Use
There is no FDA guidance on the use of Glofitamab-gxbm in geriatric settings.
Gender
There is no FDA guidance on the use of Glofitamab-gxbm with respect to specific gender populations.
Race
There is no FDA guidance on the use of Glofitamab-gxbm with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Glofitamab-gxbm in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Glofitamab-gxbm in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Glofitamab-gxbm in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Glofitamab-gxbm in patients who are immunocompromised.
Administration and Monitoring
Administration
COLUMVI (glofitamab) is administered intravenously and involves a detailed preparation and dosing schedule to mitigate the risk of Cytokine Release Syndrome (CRS). The administration begins with pretreatment using a single 1,000 mg dose of obinutuzumab, given intravenously seven days prior to starting COLUMVI. The step-up dosing schedule of COLUMVI starts on Cycle 1 Day 8 with a 2.5 mg dose administered over four hours, followed by a 10 mg dose on Cycle 1 Day 15, also over four hours. From Cycle 2 to Cycle 12, a 30 mg dose is administered on Day 1 of each 21-day cycle over two hours. The preparation of COLUMVI involves using aseptic techniques, inspecting the solution for particulate matter and discoloration, and diluting it appropriately in an infusion bag. The infusion bag should be gently inverted to mix the solution without shaking, and the diluted solution should be used immediately or stored under specified conditions if not used right away.
Monitoring
Monitoring during and after the administration of COLUMVI is crucial to ensure patient safety and manage potential adverse reactions. Patients must be adequately hydrated before administration and premedicated to reduce the risk of CRS and infusion-related reactions. The infusion should be conducted in a healthcare setting equipped to manage severe adverse reactions. During the infusion, patients should be monitored closely for signs of CRS, such as fever, chills, hypotension, and hypoxia, and for at least 24 hours after completion of the 2.5 mg and 10 mg step-up doses. Subsequent doses require hospitalization and close observation, especially for patients who experienced CRS with previous doses. Regular clinical evaluations are necessary to assess the efficacy and safety of the treatment, and any adverse reactions should be managed according to current guidelines.
IV Compatibility
Yes, COLUMVI (glofitamab) is compatible with intravenous (IV) administration. The preparation involves diluting the required volume of COLUMVI into an infusion bag containing 0.9% Sodium Chloride Injection or 0.45% Sodium Chloride Injection to a final concentration of 0.1 mg/mL to 0.6 mg/mL.
Overdosage
There is limited information regarding Glofitamab-gxbm overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Glofitamab-gxbm Pharmacology in the drug label.
Mechanism of Action
COLUMVI (glofitamab) is a bispecific CD20-directed CD3 T-cell engager designed to target and eliminate B-cell malignancies. Its mechanism of action involves binding to CD20, a protein expressed on the surface of B-cells, and CD3, a component of the T-cell receptor complex on T-cells. By engaging both targets simultaneously, COLUMVI brings T-cells into close proximity with B-cells, thereby facilitating T-cell activation and subsequent B-cell lysis. This targeted approach leverages the body’s immune system to specifically attack and destroy cancerous B-cells while minimizing damage to other cells.
Structure
There is limited information regarding Glofitamab-gxbm Structure in the drug label.
Pharmacodynamics
The pharmacodynamics of COLUMVI are centered around its ability to induce T-cell mediated cytotoxicity against CD20-expressing B-cells. Upon administration, glofitamab binds to CD20 on malignant B-cells and CD3 on T-cells, resulting in T-cell activation, proliferation, and targeted killing of B-cells. This engagement leads to the release of cytokines, which further enhance the immune response against the tumor. The reduction in B-cell numbers, including malignant cells, is associated with clinical improvements in patients with B-cell lymphomas. The pharmacodynamic effects are closely monitored to manage potential adverse reactions such as Cytokine Release Syndrome (CRS), which is indicative of the drug’s potent immunological activity.
Pharmacokinetics
The pharmacokinetics of COLUMVI involve its absorption, distribution, metabolism, and excretion. Following intravenous administration, glofitamab exhibits a multi-phase pharmacokinetic profile. The drug shows a rapid initial distribution phase followed by a slower elimination phase. The apparent volume of distribution is relatively small, indicating limited distribution beyond the vascular and interstitial compartments. Glofitamab is not metabolized by cytochrome P450 enzymes but is instead degraded into small peptides and amino acids through proteolytic pathways typical for monoclonal antibodies. The clearance of glofitamab is mediated through cellular catabolism, with a half-life that supports its dosing schedule of every three weeks after the initial step-up doses.
Nonclinical Toxicology
There is limited information regarding Glofitamab-gxbm Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Glofitamab-gxbm Clinical Studies in the drug label.
How Supplied
There is limited information regarding Glofitamab-gxbm How Supplied in the drug label.
Storage
There is limited information regarding Glofitamab-gxbm Storage in the drug label.
Images
Drug Images
{{#ask: Page Name::Glofitamab-gxbm |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}
Package and Label Display Panel
{{#ask: Label Page::Glofitamab-gxbm |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}
Patient Counseling Information
There is limited information regarding Glofitamab-gxbm Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Glofitamab-gxbm interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding Glofitamab-gxbm Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Glofitamab-gxbm Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.