Dosing & Uses
Dosage Forms & Strengths
injection, lyophilized powder for reconstitution
- 100mg/single-dose vial
Multiple Myeloma
On November 22, 2022, the drug company is following the request of the FDA and has initiated the withdrawal process of the US marketing authorization for belantamab mafodotin
Request was based on the previously announced outcome of the DREAMM-3 phase III trial, which did not meet the requirements of the FDA accelerated approval regulations
Approved for monotherapy treatment for adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least 4 prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent
Patients already enrolled in the Blenrep Risk Evaluation and Mitigation Strategy (REMS) program will have the option to enroll in a compassionate use program to continue to access treatment
Further information on how to enroll patients into compassionate use program will be provided directly to REMS enrolled prescribers
Patients currently being treated should consult their healthcare provider
Dosage Modifications
Recommended dose reduction for adverse reactions
- First dose reduction: 1.9 mg/kg IV q3Weeks
- Unable to tolerate first dose reduction: Discontinue
Corneal adverse reactions
-
Grade 1
- Corneal examination finding: Mild superficial keratopathy
- Change in best-corrected visual acuity (BCVA): Decline from baseline of 1 line on Snellen visual acuity
- Continue treatment at current dose
-
Grade 2
- Corneal examination finding: Moderate superficial keratopathy
- Change in BCVA: Decline from baseline of 2 or 3 lines on Snellen visual acuity and not worse than 20/200
- Withhold until improvement in both corneal examination findings and change in BCVA to Grade ≤1 and resume at same dose
-
Grade 3
- Corneal examination finding: Severe superficial keratopathy
- Change in BCVA: Decline from baseline by >3 lines on Snellen visual acuity and not worse than 20/200
- Withhold until improvement in both corneal examination findings and change in BCVA to Grade ≤1 and resume at reduced dose
-
Grade 4
- Corneal examination finding: Corneal epithelial defect
- Change in BCVA: Snellen visual acuity worse than 20/200
- Consider permanent discontinuation; if continuing treatment, withhold until improvement in both corneal examination findings and change in BCVA to Grade ≤1 and resume at reduced dose
Thrombocytopenia
-
Platelet count 25,000 to <50,000/mcL
- Consider withholding and/or reducing dose
-
Platelet count <25,000
- Withhold until platelet count improves to Grade ≤3; consider resuming at a reduced dose
Infusion-related reactions
-
Grade 2 or 3
- Interrupt infusion and provide supportive care
- Once symptoms resolve, resume at lower infusion rate; reduce infusion rate by at least 50%
-
Grade 4
- Permanently discontinue and provide emergency care
Other adverse reactions
-
Grade 3
- Withhold until improvement to Grade ≤1
- Consider resuming at a reduced dose
-
Grade 4
- Consider permanent discontinuation
- If continuing treatment, withhold until improvement to Grade ≤1 and resume at reduced dose
Renal impairment
- Mild-to-moderate (eGFR 30-89 mL/min/1.73m2): No dosage adjustment necessary
- Severe or end-stage renal disease not on dialysis (eGFR <29 mL/min/1.73m2): Recommended dosage has not been established
Hepatic impairment
- Mild (total bilirubin ≤1.5x ULN and any AST): No dosage adjustment necessary
- Moderate-to-severe (total bilirubin >1.5x ULN and any AST): Recommended dosage has not been established
Dosing Considerations
Perform an ophthalmic examination before initiation and during treatment
Advise patients to use preservative-free lubricant eye drops and avoid contact lenses unless directed by an ophthalmologist
Safety and efficacy not established
Adverse Effects
>10%
All grades
- Keratopathy (71%)
- Platelets decreased (62%)
- AST increased (57%)
- Decreased visual acuity (53%)
- Lymphocytes decreased (49%)
- Albumin decreased (43%)
- Glucose increased (38%)
- Hemoglobin decreased (32%)
- Creatinine increased (28%)
- Neutrophils decreased (28%)
- Alkaline phosphatase increased (26%)
- Gamma-glutamyl transferase increased (25%)
- Nausea (24%)
- Blurred vision (22%)
- Pyrexia (22%)
- Creatinine phosphokinase increased (22%)
- Sodium decreased (21%)
- Infusion-related reactions (21%)
- Fatigue (20%)
- Potassium decreased (20%)
- Dry eyes (14%)
- Constipation (13%)
- Diarrhea (13%)
- Arthralgia (12%)
- Decreased appetite (12%)
- Back pain (11%)
- Upper respiratory tract infection (11%)
Grade 3-4
- Keratopathy (44%)
- Decreased visual acuity (28%)
- Lymphocytes decreased (22%)
- Platelets decreased (21%)
- Hemoglobin decreased (18%)
1-10%
All grades
- Photophobia (<10%)
- Eye irritation (<10%)
- Infective keratitis (<10%)
- Ulcerative keratitis (<10%)
- Vomiting (<10%)
- Pneumonia (<10%)
- Albuminuria (<10%)
Grade 3-4
- Neutrophils decreased (9%)
- Creatinine increased (5%)
- Gamma-glutamyl transferase increased (5%)
- Blurred vision (4%)
- Albumin decreased (4%)
- Infusion-related reactions (3%)
- Pyrexia (3%)
- Glucose increased (3%)
- AST increased (2%)
- Sodium decreased (2%)
- Potassium decreased (2%)
- Fatigue (2%)
- Back pain (2%)
- Alkaline phosphatase increased (1%)
- Creatinine phosphokinase increased (1%)
- Dry eyes (1%)
- Diarrhea (1%)
Postmarketing Reports
Pneumonitis (including fatal cases)
Warnings
Black Box Warnings
Ocular toxicity
- May cause corneal epithelium changes resulting in vision changes, including severe vision loss, corneal ulcer, and visual symptoms (eg, blurred vision, dry eyes)
- Conduct ophthalmic examinations at baseline, before each dose, and promptly for worsening symptoms
- Withhold until improvement and resume, or permanently discontinue, based on severity
- Owing to ocular toxicity, available only through a restricted program under a REMS program called the BLENREP REMS
Blenrep REMS
-
Notable requirements include the following:
- Prescribers must be certified with the program by enrolling and completing training
- Prescribers must counsel patients about risk of ocular toxicity and need for ophthalmic examinations before each dose
- Patients must be enrolled and comply with monitoring
- Healthcare facilities must be certified with the program and verify patients are authorized to receive belantamab mafodotin
- Wholesalers and distributors must only distribute to certified healthcare facilities
- Further information is available, at www.BLENREPREMS.com and 1-855-209-9188
Contraindications
None
Cautions
Severe ocular adverse reactions occurred in clinical trials; changes in visual acuity may be associated with difficulty driving and reading; advise patients to use caution when driving or operating machinery; only available through restricted REMS program
Thrombocytopenia reported; perform CBC counts at baseline and during treatment as clinically indicated
Infusion-related reactions reported; monitor for infusion-related reactions; if reactions occurs, administer premedication for all subsequent infusion
May cause fetal harm when administered to pregnant females
Pregnancy & Lactation
Pregnancy
Based on its mechanism of action, fetal harm may occur when administered to pregnant females; contains genotoxic compound (the microtubule inhibitor, monomethyl auristatin phenylalanine [MMAF]) that targets actively dividing cells
Human IgG is known to cross the placenta; therefore, belantamab mafodotin has the potential to be transmitted from mother to developing fetus
No data available on use in pregnant females to evaluate for drug-associated risks
No animal reproduction studies were conducted
Advise pregnant females of potential risks
Recommend pregnancy testing for females of reproductive potential before initiating treatment
Contraception
- Females of reproductive potential: Use effective contraception during treatment and for 4 months after last dose
- Males with female partners of reproductive potential: Use effective contraception during treatment and for 6 months after last dose
Infertility
- Based on findings in animal studies, may impair fertility in females and males
- Effects were not reversible in male rats, but were reversible in female rats
Lactation
There is no data on presence in human milk or effects on breastfed children or milk production
Advise women not to breastfeed during treatment and for 3 months after last dose
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
An ADC consisting of an afucosylated, humanized monoclonal antibody, directed against the B-cell maturation antigen (BCMA), conjugated to the auristatin analogue and microtubule inhibitor MMAF, with potential antineoplastic activity
The anti-BCMA antibody moiety selectively binds to the BCMA on tumor cell surfaces; upon internalization, the MMAF moiety binds to tubulin and inhibits its polymerization, which results in G2/M phase arrest and induces tumor cell apoptosis
Absorption
Peak plasma concentration: 42 mcg/mL
Peak plasma time: 0.78 hr
Plasma trough concentration: 2.4 mcg/mL
AUC: 4,666 mcg⋅hr/mL
Distribution
Vd: 11 L
Metabolism
Monoclonal antibody portion is expected to be metabolized into small peptides and individual amino acids by catabolic pathway
cysmcMMAF is mainly hydrolyzed and dehydrated to a cyclized isomeric form of cys-mcMMAF
Elimination
Half-life: 12 days (first dose); 14 days (steady-state)
Administration
IV Incompatibilities
Do not mix or administer as an infusion with other products
IV Compatibilities
0.9% NaCl
IV Preparation
Hazardous drug; follow applicable special handling and disposal procedures
Calculate dose (mg), total volume (mL) of solution required, and number of vials needed based on patient’s actual body weight
More than 1 vial may be needed for a full dose; do not round down for partial vials
Reconstitution
- Remove vial(s) from refrigerator and allow to stand for ~10 minutes to reach room temperature (68-77ºF [20-25ºC])
- Reconstitute each 100-mg vial with 2 mL of sterile water for injection to obtain a final concentration of 50 mg/mL
- Gently swirl vial to aid dissolution; do not shake
- Visually inspect for particulate matter and discoloration before administration, whenever solution and container permit; reconstituted solution should be clear to opalescent, colorless to yellow to brown liquid
- Discard if extraneous particulate matter is observed
Dilution
- Withdraw calculated drug volume and dilute in a 250-mL infusion bag of 0.9% NaCl, to a final concentration of 0.2-2 mg/mL
- Infusion bags must be made of polyvinylchloride (PVC) or polyolefin (PO)
- Mix diluted solution by gentle inversion; do not shake
- Discard any unused reconstituted solution left in vial(s)
- Visual inspect for particulate matter and discoloration before administration, whenever solution and container permit; diluted infusion solution should be clear and colorless; discard if particulate matter is observed
IV Administration
If refrigerated, allow diluted infusion solution to equilibrate to room temperature (68-77ºF [20-25ºC]) before administration
Diluted infusion solution may be kept at room temperature for no more than 6 hr (including infusion time)
Administer by IV infusion over ~30 minutes using an infusion set made of PVC or PO
Filtration of the diluted solution is not required; however, if filtered, use a polyethersulfone-based filter (0.2 micron)
Do not mix or administer as an infusion with other products
Product does not contain a preservative
Storage
Hazardous drug; follow applicable special handling and disposal procedures
Unused vials
- Refrigerate at 36-46ºF (2-8ºC)
Reconstituted vials
- Refrigerate at 36-46ºF (2-8ºC) or at room temperature (68-77°F [20-25°C]) for up to 4 hr in original container; do not freeze
- Discard if not diluted within 4 hr
Diluted solutions
- Refrigerate at 36-46ºF (2-8ºC) for up to 24 hr; do not freeze
- Once removed from refrigeration, administer diluted infusion solution within 6 hr (including infusion time)
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Formulary
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