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Belantamab Mafodotin-blmf

Class: Antineoplastic Agents
- ADC
- Antibody-drug conjugate
Chemical Name: Immunoglobulin G1, anti-(Tumor necrosis factor receptor superfamily protein TNFRSF17) (humanized monoclonal GSK2857914 γ1-chain), disulfide with humanized monoclonal GSK2857914 κ-chain, dimer
Molecular Formula: C6484H10008N1728O2030S44 . (C49H66N6O11)4
CAS Number: 2050232-20-5
Brands: Blenrep

Medically reviewed by Drugs.com on Jun 7, 2021. Written by ASHP.

Warning

Ocular Toxicity

  • Changes in corneal epithelium resulting in changes in vision, including severe vision loss and corneal ulcer, and symptoms, such as blurred vision and dry eye, commonly reported.

  • Perform ophthalmic examinations at baseline, prior to each dose, and promptly for worsening symptoms.

  • If ocular toxicity occurs, temporary interruption, dosage reduction, or permanent discontinuance of therapy may be necessary. (See Dosage Modification for Toxicity under Dosage and Administration and also see Ocular Effects under Cautions.)

Risk Evaluation and Mitigation Strategy (REMS):

FDA approved a risk evaluation and mitigation strategy (REMS) for belantamab mafodotin-blmf to ensure that the benefits outweigh the risks. The REMS may apply to one or more preparations of belantamab mafodotin-blmf and consists of the following: a communication plan, elements to assure safe use, and an implementation system. See https://www.accessdata.fda.gov/scripts/cder/rems/.

Introduction

Antineoplastic agent; anti-B-cell maturation antigen (BCMA) antibody conjugated with the microtubule inhibitor monomethyl auristatin F (MMAF).

Uses for Belantamab Mafodotin-blmf

Multiple Myeloma

Treatment of relapsed or refractory multiple myeloma in adults previously treated with ≥4 prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent (designated an orphan drug by FDA for use in the treatment of multiple myeloma).

Accelerated approval based on response rate; continued approval may be contingent upon verification and description of clinical benefit in a confirmatory study.

Belantamab Mafodotin-blmf Dosage and Administration

General

  • Perform ophthalmic examinations prior to initiation of belantamab mafodotin and during therapy. Advise patients to use preservative-free ocular lubricant drops during therapy. Avoid contact lens use during therapy unless directed by an ophthalmologist. (See Ocular Effects under Cautions.)

  • Administer premedication prior to subsequent infusions if grade 2 or 3 infusion-related reactions occur.

    Consult specialized references for procedures for proper handling (e.g., use of gloves and protective clothing) and disposal of antineoplastic agents.

Restricted Distribution Program

  • Distribution of belantamab mafodotin-blmf is restricted because of the risks of ocular toxicity.

  • Must be obtained through a restricted distribution program (Blenrep REMS).

  • For details on program requirements, contact manufacturer at 855-209-9188 or visit Blenrep REMS website ([Web]).

Administration

IV Administration

Administer by IV infusion through polyvinyl chloride (PVC) or polyolefin infusion sets. If an inline filter is used, the manufacturer states that a 0.2-µm polyethersulfone (PES) inline filter should be used.

Belantamab mafodotin-blmf powder for injection must be reconstituted and diluted prior to administration.

Do not mix with or administer through the same IV line with other drugs.

Reconstitution

Following removal from refrigeration, allow vials to sit for approximately 10 minutes to reach room temperature (20–25°C). Reconstitute vial containing 100 mg of belantamab mafodotin-blmf with 2 mL of sterile water for injection to provide a solution containing 50 mg/mL. Gently swirl vial to ensure dissolution; do not shake reconstituted solution.

Reconstituted solution should be clear to opalescent, colorless to yellow to brown, and free of visible particulates.

Dilution

Dilute appropriate volume of reconstituted solution in a PVC or polyolefin infusion bag containing 250 mL of 0.9% sodium chloride injection to yield a final concentration of 0.2–2 mg/mL. Mix the diluted solution by gentle inversion; do not shake. Discard any partially used vials.

Diluted solution should be clear and colorless, and free of visible particulates.

Rate of Administration

Administer by IV infusion over 30 minutes.

If infusion-related reactions occur, reduction in infusion rate may be necessary. (See Dosage Modification for Toxicity under Dosage and Administration.)

Dosage

Calculate dose based on actual body weight. Multiple vials may be necessary for a full dose; do not round calculated dose down to the nearest whole vial.

Adults

Multiple Myeloma
IV

2.5 mg/kg every 3 weeks. Continue until disease progression or unacceptable toxicity occurs.

Dosage Modification for Toxicity

Temporary interruption, dosage reduction, and/or discontinuance may be necessary for adverse reactions. If a dosage reduction is required, reduce dosage to 1.9 mg/kg once every 3 weeks; discontinue therapy if reduced dosage is not tolerated.

Ocular Effects

If corneal adverse effects (e.g., keratopathy, decreased visual acuity) occur, temporarily interrupt therapy, reduce dosage, and/or permanently discontinue belantamab mafodotin therapy as described in Table 1. Determine dosage modification based on the worst finding on either a corneal examination or change in visual acuity (according to the Keratopathy and Visual Acuity [KVA] scale) in the worst affected eye.

a With or without patchy microcyst-like deposits, peripheral subepithelial haze, or new peripheral stromal opacity

b With or without diffuse microcyst-like deposits, central subepithelial haze, or a new central stromal opacity

Table 1: Recommended Dosage Modification for Corneal Adverse Effects1

Severity

Findings

Dosage Modification

Grade 1

Mild superficial keratopathy (with or without symptoms) or decrease in visual acuity (reduction by 1 line from baseline on Snellen Visual Acuity)

Continue therapy at same dosage

Grade 2

Moderate superficial keratopathya or decrease in visual acuity (reduction by 2 or 3 lines from baseline on Snellen Visual Acuity, but no worse than 20/200)

Withhold therapy; when corneal examination findings and change in best-corrected visual acuity improve to grade 1 or less, resume at same dosage

Grade 3

Severe superficial keratopathyb or decrease in visual acuity (reduction by >3 lines from baseline on Snellen Visual Acuity, but no worse than 20/200)

Withhold therapy; when corneal examination findings and change in best-corrected visual acuity improve to grade 1 or less, resume at reduced dosage

Grade 4

Corneal epithelial defect (e.g., corneal ulcers) or Snellen Visual Acuity worse than 20/200

Consider permanently discontinuing therapy

If continuing therapy, withhold drug until corneal examination findings and change in best-corrected visual acuity improve to grade 1 or less, then resume at reduced dosage

Hematologic Toxicity

If platelet count 25,000 to <50,000/mm3 occurs, consider withholding therapy and/or dosage reduction.

If platelet count <25,000/mm3 occurs, withhold therapy until thrombocytopenia improves to grade 3 or less, then consider resuming at reduced dosage. (See Hematologic Effects under Cautions.)

Infusion-related Reactions

If grade 2 or 3 infusion-related reactions occur, interrupt infusion and provide appropriate supportive therapy; once reaction has resolved, resume infusion and reduce infusion rate by at least 50%.

If grade 4 or life-threatening infusion-related reactions occur, permanently discontinue drug and provide appropriate emergency care. (See Infusion-related Effects under Cautions.)

Other Adverse Effects

If other grade 3 adverse effects occur, withhold therapy; when toxicity improves to grade 1 or less, resume at reduced dosage.

If grade 4 adverse reactions occur, permanently discontinue drug. If continuation of belantamab mafodotin therapy is desired, withhold therapy until toxicity improves to grade 1 or less, then resume therapy at reduced dosage.

Special Populations

Hepatic Impairment

Mild hepatic impairment (total bilirubin concentrations not exceeding the ULN with AST concentrations exceeding the ULN, or total bilirubin concentrations exceeding the ULN but ≤1.5 times the ULN with any AST concentration): No dosage adjustment required.

Moderate or severe hepatic impairment (total bilirubin >1.5 times the ULN and any AST): No specific dosage recommendations. (See Hepatic Impairment under Cautions.)

Renal Impairment

Mild or moderate renal impairment (eGFR 30–89 mL/minute per 1.73 m2): No dosage adjustment required.

Severe renal impairment (eGFR 15–29 mL/minute per 1.73 m2) or end-stage renal disease (with or without dialysis): No specific dosage recommendations. (See Renal Impairment under Cautions.)

Geriatric Patients

No specific dosage recommendations. (See Geriatric Use under Cautions.)

Cautions for Belantamab Mafodotin-blmf

Contraindications

  • None.

Warnings/Precautions

Warnings

Ocular Effects

Ocular adverse effects (i.e., keratopathy, changes in visual acuity, blurred vision, dry eye) occur frequently. Most keratopathy events develop within the first 2 treatment cycles and resolve over the course of days to months. Decreased visual acuity of 20/200 or worse resolved in all patients in a median of 22 days.

Advise patients to use preservative-free ocular lubricant drops ≥4 times daily starting with the first infusion and continuing until discontinuance of therapy. Avoid contact lens use unless directed by an ophthalmologist. (See Advice to Patients.)

Perform ophthalmic examinations (visual acuity and slit lamp) at baseline, prior to each dose, and promptly for worsening symptoms. Perform baseline examinations within 3 weeks prior to the first dose. Perform subsequent examinations ≥1 week after the previous dose and within 2 weeks prior to the next dose. Temporary interruption, dosage reduction, and/or discontinuance may be necessary. (See Dosage Modification for Toxicity under Dosage and Administration.)

Because of the risk of ocular toxicity, must be obtained through a restricted distribution program (Blenrep REMS). (See Restricted Distribution Program under Dosage and Administration.)

Other Warnings and Precautions

Hematologic Effects

Thrombocytopenia and hemorrhagic events reported. The median time to initial onset of thrombocytopenia was 26.5 days.

Monitor CBC at baseline and as clinically indicated. Temporary interruption and/or dosage reduction may be necessary. (See Dosage Modification for Toxicity under Dosage and Administration.)

Infusion-Related Effects

Infusion-related reactions reported.

Monitor for infusion-related reactions. For grade 2 or 3 infusion-related reactions, interrupt the infusion and provide supportive care. Resume infusion at a slower infusion rate once symptoms resolve, and administer premedication prior to all subsequent infusions. If life-threatening infusion-related reactions occur, permanently discontinue therapy and provide emergency care. (See Dosage Modification for Toxicity under Dosage and Administration.)

Fetal/Neonatal Morbidity and Mortality

Based on mechanism of action, belantamab mafodotin may cause fetal harm.

Avoid pregnancy during therapy. Perform pregnancy testing prior to initiation of therapy in females of reproductive potential. Advise females of reproductive potential to use effective contraception while receiving the drug and for 4 months after the last dose. Men with such female partners should use effective contraception while receiving the drug and for 6 months after the last dose. If used during pregnancy or if patient becomes pregnant, apprise patient of potential fetal hazard.

Immunogenicity

Potential for immunogenicity. Data insufficient to determine whether antibody formation affects pharmacokinetics, efficacy, or safety.

Impairment of Fertility

Results of animal studies suggest belantamab mafodotin may impair female and male fertility.

Specific Populations

Pregnancy

May cause fetal harm. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether belantamab mafodotin is distributed into milk, affects breast-fed infants, or affects milk production. Discontinue nursing during therapy and for 3 months after the last dose.

Pediatric Use

Safety and efficacy not established in pediatric patients.

Geriatric Use

Experience is insufficient to determine whether geriatric patients respond differently than younger patients.

Hepatic Impairment

Mild hepatic impairment (total bilirubin not exceeding the ULN with AST exceeding the ULN, or total bilirubin exceeding the ULN but ≤1.5 times ULN with any AST): Pharmacokinetics not substantially altered. No dosage adjustment needed.

Moderate or severe hepatic impairment (total bilirubin concentration >1.5 times the ULN with any AST concentration): Pharmacokinetics not studied.

Renal Impairment

Mild or moderate renal impairment (eGFR 30–89 mL/minute per 1.73 m2): Pharmacokinetics not substantially altered. No dosage adjustment needed.

Severe renal impairment (eGFR 15–29 mL/minute per 1.73 m2) or end-stage renal disease (with or without dialysis): Pharmacokinetics not studied.

Common Adverse Effects

Keratopathy, decreased visual acuity, nausea, blurred vision, pyrexia, infusion-related reactions, fatigue, decreased platelets, decreased lymphocytes, decreased hemoglobin, decreased neutrophils, increased creatinine, increased γ-glutamyl transferase (GGT, γ-glutamyltranspeptidase, GGTP).

Interactions for Belantamab Mafodotin-blmf

No formal drug interaction studies performed; however, risk of clinically relevant drug interactions appears minimal.

MMAF is a substrate of organic anion transporting polypeptide (OATP) 1B1, OATP1B3, multidrug resistance-associated protein (MRP) 1, MRP2, MRP3, bile salt export pump (BSEP), and possibly P-glycoprotein (P-gp).

Cys-mcMMAF (the microtubule inhibitor and linker following release from the monoclonal antibody) is not a sensitive substrate of CYP isoenzymes and does not inhibit or induce CYP isoenzymes. Belantamab mafodotin is not likely to modulate cytokines involved in suppression of CYP isoenzymes or transporters.

Belantamab Mafodotin-blmf Pharmacokinetics

Absorption

Bioavailability

Exhibits dose-proportional pharmacokinetics.

Peak plasma concentrations of the antibody-drug conjugate are attained at or shortly after the end of IV infusion; peak plasma concentrations of cys-mcMMAF are attained approximately 23 hours after IV infusion.

Steady-state concentrations reached in approximately 70 days; accumulation of antibody-drug conjugate is approximately 70% following repeated administration.

Special Populations

Mild hepatic impairment (total bilirubin not exceeding the ULN with AST exceeding the ULN, or total bilirubin >1 to 1.5 times the ULN with any AST): Pharmacokinetics not substantially altered.

Moderate or severe hepatic impairment (total bilirubin concentration >1.5 times the ULN with any AST concentration): Pharmacokinetics not studied.

Mild or moderate renal impairment (eGFR 30–89 mL/minute per 1.73 m2): Pharmacokinetics not substantially altered.

Severe renal impairment (eGFR 15–29 mL/minute per 1.73 m2) or end-stage renal disease (with or without dialysis): Pharmacokinetics not studied.

Age (34–89 years), sex, race (White or Black), and body weight (42–130 kg) do not substantially affect pharmacokinetics of belantamab mafodotin.

Distribution

Extent

Not known whether belantamab mafodotin is distributed into milk.

Plasma Protein Binding

cys-mcMMAF: Low binding (concentration dependent).

Elimination

Metabolism

Antibody-drug conjugate: Degrades into small peptides and amino acids via catabolic pathways.

cys-mcMMAF: Mainly hydrolyzed and dehydrated to a cyclized isomeric form of cys-mcMMAF.

Elimination Route

cys-mcMMAF: Eliminated in feces (83%) and urine (13%).

Half-life

Antibody-drug conjugate: 12 days after first dose and 14 days at steady state.

Stability

Storage

Parenteral

Powder for Injection

2–8°C in original carton. Do not freeze or shake.

Reconstituted drug: May store at 2–8 or 20–25°C for up to 4 hours. Do not freeze or shake.

Diluted infusion solution: May store at 2–8°C for up to 24 hours. Do not freeze or shake. Once removed from refrigeration, use within 6 hours (including infusion time).

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility

Compatible

Sodium chloride 0.9%

Actions

  • An anti-BCMA antibody conjugated with the microtubule inhibitor MMAF via a protease-resistant maleimidocaproyl linker.

  • Approximately 4 molecules of MMAF are attached to each antibody molecule.

  • The antibody-drug conjugate binds to BCMA, the resultant complex is internalized by the cell, and MMAF is released via proteolytic cleavage resulting in disruption of the intracellular microtubule network and cell cycle arrest and apoptosis.

Advice to Patients

  • Advise the patient to read the FDA-approved patient labeling (Medication Guide).

  • Advise patients that ocular toxicity may occur during treatment with belantamab mafodotin-blmf. Importance of complying with ongoing monitoring for eye exams.

  • Advise patients to administer preservative-free ocular lubricant drops as recommended during treatment and to avoid wearing contact lenses during treatment unless directed by a healthcare professional.

  • Advise patients to use caution when driving or operating machinery, since belantamab mafodotin-blmf may adversely affect their vision.

  • Importance of educating patients regarding the Blenrep REMS restricted distribution program for obtaining belantamab mafodotin-blmf. (See Restricted Distribution Program under Dosage and Administration.)

  • Advise patients to inform their healthcare provider if they develop signs or symptoms of bleeding.

  • Advise patients to immediately report any signs and symptoms of infusion-related reactions to their healthcare provider.

  • Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy.

  • Advise women of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose.

  • Advise males with female partners of reproductive potential to use effective contraception during treatment with belantamab mafodotin-blmf and for 6 months after the last dose.

  • Advise women not to breast-feed during treatment with belantamab mafodotin-blmf and for 3 months after the last dose.

  • Advise males and females of reproductive potential that belantamab mafodotin-blmf may impair fertility.

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Distribution of belantamab mafodotin-blmf is restricted. (See Restricted Distribution Program under Dosage and Administration.)

Belantamab Mafodotin-blmf

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV infusion only

100 mg

Blenrep

GlaxoSmithKline

AHFS DI Essentials™. © Copyright 2021, Selected Revisions June 7, 2021. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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