Usual Adult Dose for Multiple Myeloma

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

Use: 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

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 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.

• 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.

• 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 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 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 reduced dose.

• Platelet count 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 reduced dose.

• 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.

• GRADE 3: Withhold therapy until improvement to Grade 1 or less; consider resuming at 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 reduced dose.

Precautions

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for Blenrep. It includes a communication plan, elements to assure safe use, and implementation system. For additional information: http://www.accessdata.fda.gov/scripts/cder/rems/index.cfm

US BOXED WARNINGS:
OCULAR TOXICITY: This drug causes changes in the corneal epithelium resulting in changes in vision, including severe vision loss and corneal ulcer, and symptoms, such as blurred vision and dry eyes.
Recommendations:

• Conduct ophthalmic exams at baseline, prior to each dose, and promptly for worsening symptoms.
• Withhold this drug until improvement and resume, or permanently discontinue, based on severity.
• This drug is available only through a restricted program, called the BLENREP REMS.

• None

Dialysis

Data not available

Other Comments

Administration advice:

• Perform an ophthalmic exam prior to initiation of this drug and during therapy.

• Store vials refrigerated at 36F to 46F (2C to 8C).
• If the diluted infusion solution is not used immediately, store refrigerated at 36F to 46F (2C to 8C) for up to 24 hours. Do not freeze. When removed from refrigeration, administer the diluted infusion solution within 6 hours (including infusion time).

• Reconstitute this drug with sterile water for injection.
• The manufacturer product information should be consulted.

• This drug is hazardous; follow applicable special handling and disposal procedures.

• Use preservative-free lubricant eye drops and avoid contact lenses unless directed by an ophthalmologist.