Belantamab mafodotin – Uses, Dosage, Side Effects, Interactions

Mechanism of action

Belantamab mafodotin is a humanized IgG1κ monoclonal antibody against the B-cell maturation antigen (BCMA) conjugated with a cytotoxic agent, maleimidocaproyl monomethyl auristatin F (mcMMAF).^[rx] The antibody-drug conjugate binds to BCMA on myeloma? cell surfaces causing cell cycle arrest and inducing antibody-dependent cellular cytotoxicity.^[rx]

Belantamab mafodotin, or GSK2857916, is a fucosylated monoclonal antibody that targets B cell maturation antigen (BCMA) conjugated to the microtubule disrupter monomethyl auristatin-F (MMAF).^[rx] Afucosylation of the Fc region of monoclonal antibodies enhances binding to the Fc region, which enhances antibody-dependant cell-mediated cytotoxicity.^[rx]

BCMA is uniquely expressed in CD138-positive myeloma cells.^[rx] Targeting BCMA allows belantamab mafodotin to be highly selective in its delivery of MMAF to multiple myeloma cells^[rx] Belantamab mafodotin binds to BCMA, is internalized into cells, and releases MMAF.^[rx]

The MMAF payload binds to tubulin, stopping the cell cycle at the DNA damage checkpoint between the G2 and M phases, resulting in apoptosis.^[rx]

Belantamab mafodotin treats multiple myeloma through antibody dependant cell-mediated cytotoxicity as well as G2/M cell cycle arrest.^[rx] It has a narrow therapeutic? index due to the incidence of adverse effects, and a long duration of action as it is given every 3 weeks.^[rx] Patients should be counseled regarding the risk of keratopathy.^[rx]

Indication?

• Belantamab mafodotin is indicated in the treatment of adults with relapsed or refractory multiple myeloma who have received at least 4 prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent.^[rx]
• Relapsed Or Refractory Multiple Myeloma
• Belantamab mafodotin is indicated for the treatment of adults with relapsed or refractory multiple myeloma who have received at least four prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent
• For treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 4 prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent.

Use in Cancer

Belantamab mafodotin-blmf is approved to treat:

• Multiple myeloma that has relapsed (come back) or is refractory (does not respond to treatment). It is used in adults who have received at least four previous treatments that included an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulating agent.

Belantamab mafodotin-blmf is only available as part of a special program called Blenrep REMS (Risk Evaluation and Mitigation StrategiesExit Disclaimer).

This use is approved under FDA’s Accelerated Approval Program. As a condition of approval, a confirmatory trial(s) must show that belantamab mafodotin-blmf provides a clinical? benefit in these patients.

Contraindication?

The following conditions are contraindicated? with this drug. Check with your physician if you have any of the following:

• decreased blood platelets
• a decrease in sharpness of vision called reduced visual acuity?
• pregnancy
• a patient who is producing milk and breastfeeding

Dosage?

Strengths: blmf 100 mg

Multiple Myeloma

• 2.5 mg/kg (of actual body weight) IV over 30 minutes once every 3 weeks until disease progression? or unacceptable toxicity

Renal? Dose Adjustments

• Mild? (CrCl 60 to less than 90 mL/min) or moderate? (CrCl 30 to less than 60 mL/min) renal impairment: No adjustment recommended.
  Severe? (CrCl 15 to less than 30 mL/min) or end-stage? (CrCl less than 15 mL/min) renal impairment: Data not available

Liver? Dose Adjustments

• Mild hepatic impairment (total bilirubin? less than or equal to the upper limit of normal [ULN] and aspartate aminotransferase (AST) greater than ULN or total bilirubin 1 to less than or equal to 1.5 x ULN and any AST): No adjustment recommended.
  Moderate or severe hepatic impairment (total bilirubin greater than 1.5 x ULN and any AST): Data not available

Dose Adjustments

DOSE MODIFICATIONS FOR ADVERSE REACTIONS:

• The recommended dose reduction for adverse reactions is: 1.9 mg/kg IV once every 3 weeks; discontinue therapy in patients who are unable to tolerate a dose of 1.9 mg/kg.

CORNEAL ADVERSE REACTIONS:

• The recommended dosage modifications for corneal adverse reactions are based on both corneal examination findings and changes in best-corrected visual acuity (BCVA).
• Determine the dose modification based on the worst finding in the worst affected eye. Worst finding should be based on either a corneal examination finding or a change in visual acuity per the Keratopathy and Visual Acuity (KVA) scale.

DOSE MODIFICATIONS FOR CORNEAL ADVERSE REACTIONS PER THE KVA SCALE CORNEAL ADVERSE REACTION:

• GRADE 1 (mild superficial keratopathy with or without symptoms?; change in BCVA: decline from baseline? of 1 line on Snellen Visual Acuity: Continue therapy at the current dose.
• GRADE 2: (moderate superficial keratopathy with or without patchy microcyst-like deposits, sub-epithelial haze [peripheral], or a new peripheral stromal opacity; change in BCVA: decline from baseline of 2 or 3 lines on Snellen Visual Acuity and not worse than 20/200): Withhold therapy until improvement in both corneal examination findings and change in BCVA to Grade 1 or less; resume at the same dose.
• GRADE 3 (severe superficial keratopathy with or without diffuse microcyst-like deposits, sub-epithelial haze (central), or a new central stromal opacity; change in BCVA: decline from baseline of 2 or 3 lines on Snellen Visual Acuity and not worse than 20/200): Withhold therapy until improvement in both corneal examination findings and change in BCVA to Grade 1 or less; resume at a reduced dose.
• GRADE 4 (corneal epithelial defect [e.g., corneal ulcers]; change in BCVA: Snellen Visual Acuity worse than 20/200): Consider permanent discontinuation of therapy; if continuing therapy, withhold this drug until improvement in both corneal examination findings and change in BCVA to Grade 1 or better; resume at a reduced dose.

DOSE MODIFICATIONS FOR OTHER ADVERSE REACTIONS:
THROMBOCYTOPENIA?:

• Platelet? counts 25,000 to less than 50,000/mcL: Consider withholding this drug and/or reducing the dose.
• Platelet count less than 25,000/mcL: Withhold this drug until platelet count improves to Grade 3 or less; consider resuming at a reduced dose.

INFUSION-RELATED REACTIONS:

• GRADE 2 or 3: Interrupt infusion and provide supportive care; when symptoms resolve, resume infusion rate at 50% of the previous rate.
• GRADE 4: Permanently discontinue therapy and provide emergency? care.

OTHER ADVERSE REACTIONS:

• GRADE 3: Withhold therapy until improvement to Grade 1 or less; consider resuming at a reduced dose.
• GRADE 4: Consider permanent discontinuation of therapy; if continuing therapy, withhold this drug until improvement to Grade 1 or less and resume at a reduced dose.

Side Effects

The Most Common

• nausea?
• constipation?
• diarrhea?
• loss of appetite?
• joint or back pain?
• tiredness
• unusual bleeding or bruising
• shortness of breath, chest pain, cough

More common

• Black, tarry stools
• bleeding gums
• blood in urine or stools
• blurred vision or any other change in vision
• body aches or pain
• change in color vision
• chest pain or tightness
• chills
• confusion
• constipation
• cough
• decreased frequency or amount of urine
• depression
• difficulty seeing at night
• difficulty with swallowing
• dizziness
• dry eye
• dry mouth
• ear congestion
• eye redness, irritation, or pain
• fainting
• fast heartbeat

Rare

• fever
• headache
• incoherent speech
• increased sensitivity of the eyes to sunlight
• increased thirst
• increased urination
• lightheadedness or faintness
• loss of appetite
• loss of voice
• low blood pressure or pulse
• lower back or side pain
• metallic taste
• muscle weakness
• nausea
• pinpoint red spots on the skin
• pounding in the ears
• rapid, shallow breathing
• runny or stuffy nose
• skin rash, itching, or hives
• sneezing
• sore throat
• stomach pain
• swelling in the face, hands, or lower legs
• trouble breathing
• unconsciousness
• unusual bleeding or bruising
• unusual tiredness or weakness
• vomiting
• weight gain or loss

Drug Interaction

Pregnancy and Lactation

 US FDA pregnancy category: Not assigned.

Pregnancy

The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help healthcare providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out. Based on its mechanism of action, this drug can cause fetal harm when administered to a pregnant woman, because it contains a genotoxic compound (the microtubule inhibitor, MMAF) and targets actively dividing cells. Human immunoglobulin G (IgG) is known to cross the placenta; therefore, this drug has the potential to be transmitted from the mother to the developing fetus.

Lactation

There are no data on the presence of this drug in human milk or the effects on the breastfed child or milk production. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during therapy and for 3 months after.

References