BLENREP

Antineoplastic Monoclonal Antibodies Targeting B-Cell Maturation Antigen (BCMA)
Antineoplastic Monoclonal Antibody-Drug Conjugates (ADCs)

Hazardous Drugs Classification
NIOSH (Draft) 2020 List: Table 1
Approved by FDA after NIOSH 2016 list published. The manufacturer recommends this drug be handled as a hazardous drug.
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Reconstitution:
Calculate the required dose (mg) and remove the correct number of vials from the refrigerator; let vial(s) stand for approximately 10 minutes to allow them to reach room temperature (20 to 25 degrees C or 68 to 77 degrees F).
Reconstitute each 100-mg vial with 2 mL of Sterile Water for injection for a final vial concentration of 50 mg/mL.
Gently swirl the vial to aid in dissolution; do not shake.
The vial solution should be clear to opalescent, colorless to yellow to brown liquid, and free of extraneous particulate matter.
Storage following reconstitution: Store in the original container for up to 4 hours in the refrigerator (2 to 8 degrees C or 36 to 46 degrees F) or at room temperature prior to dilution; do not freeze. Discard if not diluted within 4 hours.
Dilution:
Withdraw the calculated dose/volume from the reconstituted vial(s) and dilute in 250 mL of 0.9% Sodium Chloride injection to achieve a final concentration of 0.2 mg/mL to 2 mg/mL.
Infusion bags must be made of polyvinylchloride (PVC) or polyolefin (PO).
Discard any unused reconstituted solution left in the vial.
Mix by gently inverting the infusion bag; do not shake.
The diluted solution should be clear and colorless and free of particulate matter.
Storage following dilution: Store the diluted admixture for up to 24 hours in the refrigerator; do not freeze. Once removed from the refrigerator, administer within 6 hours (includes administration time).
Intravenous (IV) infusion:
Allow the diluted admixture to acclimate to room temperature (if applicable) prior to administration.
Administer belantamab mafodotin as an IV infusion over approximately 30 minutes using a PVC or PO infusion-set.
The diluted admixture does not require a filter for administration; if the solution is filtered, use a polyethersulfone (PES)-based 0.2-micron filter.
Do not mix or administer with other products.

visual impairment / Early / 0-77.0
keratopathy / Delayed / 0-45.5
thrombocytopenia / Delayed / 0-27.0
lymphopenia / Delayed / 0-22.0
anemia / Delayed / 0-18.0
keratitis / Delayed / 0-10.0
neutropenia / Delayed / 0-9.0
infection / Delayed / 0-7.0
bleeding / Early / 0-6.0
hypercalcemia / Delayed / 4.2-4.2
nephrotoxicity / Delayed / 0-4.2
blurred vision / Early / 0-4.0
hypoalbuminemia / Delayed / 4.0-4.0
fever / Early / 3.0-3.0
hyperglycemia / Delayed / 3.0-3.0
fatigue / Early / 2.0-2.0
back pain / Delayed / 2.0-2.0
hypophosphatemia / Delayed / 2.0-2.0
hyponatremia / Delayed / 2.0-2.0
elevated hepatic enzymes / Delayed / 0-2.0
infusion-related reactions / Rapid / 0-1.8
xerophthalmia / Early / 0-1.0
cardiac arrest / Early / 0-1.0
diarrhea / Early / 1.0-1.0
intracranial bleeding / Delayed / Incidence not known

constipation / Delayed / 13.0-13.0
photophobia / Early / 0-10.0
antibody formation / Delayed / 0-1.0
sinus tachycardia / Rapid / Incidence not known
hypertension / Early / Incidence not known
pneumonitis / Delayed / Incidence not known

nausea / Early / 24.0-24.0
anorexia / Delayed / 12.0-12.0
arthralgia / Delayed / 12.0-12.0
ocular irritation / Rapid / 0-10.0
vomiting / Early / 0-10.0
diplopia / Early / Incidence not known
ocular pruritus / Rapid / Incidence not known
sinusitis / Delayed / Incidence not known
pharyngitis / Delayed / Incidence not known
asthenia / Delayed / Incidence not known
chills / Rapid / Incidence not known
lethargy / Early / Incidence not known

Ocular toxicity/visual impairment has been reported with belantamab mafodotin therapy. It may cause serious changes in the corneal epithelium including corneal ulcer. All patients should use preservative-free lubricant eye drops at least 4 times daily during therapy starting with the first dose. Avoid use of contact lenses unless directed by an ophthalmologist. Perform an ophthalmic exam (i.e., visual acuity and slit lamp) at baseline (3 weeks prior to the first dose), prior to each dose (1 week after the previous dose and within 2 weeks prior to the next dose), and promptly for worsening symptoms. Therapy interruption, a dose reduction, or discontinuation may be necessary in patients who develop corneal toxicity or changes in visual acuity. Advise patients to use caution with driving or operating machinery due to the risk of reduced visual acuity with belantamab mafodotin therapy. Geriatric patients aged 65 and older who received with belantamab mafodotin had a higher incidence of keratopathy compared with younger patients (73% vs. 67%).

BLENREP

Rx

B-cell maturation antigen-directed antibody and microtubule inhibitor conjugate
Used in adult patients with relapsed or refractory multiple myeloma
Black box warning for severe vision changes; frequent ophthalmic exams are necessary

Dosage not established.

No dosage adjustment is necessary in patients with mild hepatic impairment (total bilirubin level of the upper limit of normal (ULN) or less and an AST level greater than the ULN OR total bilirubin level of 1 to 1.5 times the ULN and any AST level). Specific guidelines for dosage adjustments in moderate to severe hepatic impairment (total bilirubin level greater than 1.5 times the ULN and any AST level) are not available; it appears that no dosage adjustments are needed.

No dosage adjustment is necessary in patients with mild or moderate renal impairment (estimated glomerular filtration rate (eGFR) of 30 to 89 mL/min/1.73 m2). Specific guidelines for dosage adjustments in severe renal impairment (eGFR of 15 to 29 mL/min/1.73 m2) or end-stage renal disease (eGFR of less than 15 mL/min/1.73 m2) with or without dialysis are not available; it appears that no dosage adjustments are needed.

Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.

BLENREP Intravenous Inj Pwd: 100mg

2.5 mg/kg (actual body weight) IV every 3 weeks.

2.5 mg/kg (actual body weight) IV every 3 weeks.

Safety and efficacy not established.

Safety and efficacy not established.

Safety and efficacy not established.

Belantamab mafodotin is a B-cell maturation antigen (BCMA)-directed antibody and microtubule inhibitor conjugate. It has 3 components consiting of an afucosylated, humanized immunoglobulin G1 (IgG1) monoclonal antibody covalently linked to a microtubule inhibitor (monomethyl auristatin F (MMAF)) via a protease-resistant maleimidocaproyl linker. BCMA is a protein that is expressed on normal B lymphocytes and multiple myeloma cells. Belantamab mafodotin is internalized after binding to BCMA and then MMAF is released via proteolytic cleavage which causes disruption in the microtubule network and eventually cell cycle arrest and apoptosis. In vitro, MMAF-induced apoptosis and tumor lysis via antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis have been demonstrated in multiple myeloma cells.

Belantamab mafodotin is administered intravenously. It has a mean steady-state volume of distribution of 11 L (coefficient of variation (CV), 15%), a steady-state plasma clearance of 0.7 L/day (CV, 50%), and a steady-state terminal phase half-life of 14 days. The monoclonal antibody part of belantamab mafodotin is metabolized into small peptides and individual amino acids by catabolic pathways. In vitro, the small molecule microtubule inhibitor (monomethyl auristatin F (MMAF)) part of belantamab mafodotin is primarily hydrolyzed and dehydrated to a cyclized isomeric form (Cyc-mcMMAF).
Affected drug transporters: OATP1B1, OATP1B3, MRP1, MRP2, MRP3, BSEP
In vitro, Cyc-mcMMAF is a substrate of organic anion transporting polypeptide (OATP)1B1 and OATP1B3; multidrug resistance-associated protein (MRP)1, MRP2, MRP3; bile salt export pump (BSEP); it is also a possible substrate of P-glycoprotein.

Belantamab mafodotin-blmf exhibits dose-proportional pharmacokinetics; clearance gradually decreases over time. The time to reach steady-state is approximately 70 days. Following an IV dose of belantamab mafodotin 2.5 mg/kg, the mean Cmax value was 42 mcg/mL (coefficient of variation (CV), 26%), the mean Cmin value was 2.4 mcg/mL (CV, 52%), the median Tmax value was 0.78 hour (range, 0.4 to 2.5 hours), and the mean AUC value was 4,666 mcg/mL x hour (CV, 46%). Accumulation was about 70% with an every-3-week belantamab mafodotin dosing regimen.

Belantamab mafodotin may cause fetal harm if administered during pregnancy based on its mechanism of action. It is genotoxic and there is a risk of embryotoxicity and teratogenicity with this drug. Females of reproductive potential should be advised to avoid pregnancy while receiving belantamab mafodotin. Pregnant women should be apprised of the potential hazard to the fetus. Human immunoglobulin G is known to cross into the placenta; therefore, belantamab mafodotin may be transmitted from the mother to the developing fetus.

It is not known if belantamab mafodotin is secreted in human milk or if it has effects on milk production or the breastfed child. Due to the potential for serious adverse reactions in the breastfed child, advise women to avoid breast-feeding during and for 3 months after the last belantamab mafodotin dose.