Drug information of Belantamab mafodotin

Belantamab mafodotin is an afucosylated, humanized antibody-drug conjugate directed against B-cell maturation antigen (BCMA); BCMA is expressed on multiple myeloma cells but is mostly absent on naive and memory B cells (Lonial 2020). The antibody is conjugated by a protease-resistant maleimidocaproyl linker to microtubule-disrupting monomethyl auristatin F (MMAF). After binding to BCMA, belantamab mafodotin is internalized and MMAF is released via proteolytic cleavage, resulting in cell cycle arrest and apoptosis. In addition to MMAF-induced apoptosis, belantamab mafodotin causes tumor cell lysis through antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis

Metabolism
The monoclonal antibody is expected to be metabolized into small peptides and individual amino acids by catabolic pathways
Excretion
Clearance: 0.7 L/day (at steady state
Onset of Action
Median time to first response: 1.4 months
Time to Peak
Shortly after the end of the infusion
Duration of Action
Most patients had a duration of response of ≥6 months
Half-Life Elimination
14 days (at steady state); 12 days (after first dose

Multiple myeloma, relapsed or refractory: Treatment of relapsed or refractory multiple myeloma in adults who have received at least 4 prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent

Multiple myeloma, relapsed or refractory: IV: 2.5 mg/kg (based on actual body weight) once every 3 weeks until disease progression or unacceptable toxicity

None

>10%
Endocrine & metabolic: Decreased serum albumin, decreased serum potassium, decreased serum sodium, increased gamma-glutamyl transferase, increased serum glucose
Gastrointestinal: Constipation, decreased appetite, diarrhea, nausea
Hematologic & oncologic: Decreased hemoglobin, decreased neutrophils, lymphocytopenia, thrombocytopenia
Hepatic: Increased serum alkaline phosphatase, increased serum aspartate aminotransferase
Nervous system: Fatigue
Neuromuscular & skeletal: Arthralgia, asthenia, back pain, increased creatine phosphokinase in blood specimen
Ophthalmic: Blurred vision, decreased visual acuity, dry eye syndrome, epithelial keratopathy
Renal: Increased serum creatinine
Respiratory: Upper respiratory tract infection
Miscellaneous: Fever, infusion related reaction
1%
 to 10%
Endocrine & metabolic: Albuminuria, hypercalcemia
Gastrointestinal: Vomiting
Infection: Sepsis
Ophthalmic: Eye irritation, keratitis, photophobia
Renal: Renal insufficiency
Respiratory: Pneumonia
<1%
 Immunologic: Antibody development
Frequency not defined: Ophthalmic: Corneal ulcer, ocular toxicity, severe vision loss

BCG (Intravesical), Chloramphenicol (Ophthalmic), Cladribine, CloZAPine, Deferiprone,
Dipyrone, Mesalamine, Promazine

Belantamab mafodotin-blmf caused 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

Conduct ophthalmic exams at baseline, prior to each dose, and promptly for worsening symptoms. Withhold belantamab mafodotin-blmf until improvement and resume, or permanently discontinue, based on severity

The safety and effectiveness of belantamab mafodotin-blmf in pediatric patients have not been established

Bone marrow suppression: Thrombocytopenia occurred in the majority of patients, including grade 2, 3, and 4 events. The median time to onset of the first thrombocytopenic events was ~27 days. Grade 3 to 4 bleeding events occurred in a small percentage of patients; fatal cerebral hemorrhage occurred rarely. Perform CBC at baseline and during therapy as clinically necessary; thrombocytopenia may require therapy interruption or dosage reduction, based on severity. Lymphocytopenia, anemia, and neutropenia have also been reported

Infusion-related reaction: Infusion-related reactions occurred in ~20% of patients, including grade 3 reactions (rare). Monitor for infusion-related reactions. Interrupt infusion and provide supportive therapy for grade 2 or 3 reactions; once symptoms resolve, resume at a lower infusion rate and administer premedication for all subsequent infusions. Discontinue belantamab mafodotin for life-threatening infusion-related reactions and provide appropriate emergency management

Perform an ophthalmic exam prior to belantamab mafodotin initiation and during therapy. Patients should use preservative-free lubricant eye drops and avoid contact lenses unless otherwise directed

IV: Infuse over ~30 minutes using an infusion set made of PVC or polyolefin. Although not required, a polyethersulfone-based filter (0.2 micron) may be used. Do not administer with any other medications. If refrigerated, allow the diluted solution to equilibrate to room temperature prior to administration; solution must be infused within 6 hours after removal from refrigeration (including infusion time). Monitor for infusion-related reactions

Store intact vials at 2ºC to 8ºC (36ºF to 46ºF). If not used immediately, reconstituted solution may be stored at 2ºC to 8ºC (36ºF to 46ºF) or at 20ºC to 25ºC (68ºF to 77ºF) for up to 4 hours; discard if not diluted within 4 hours. Solutions diluted for infusion (if not used immediately) may be stored at 2ºC to 8ºC (36ºF to 46ºF) for up to 24 hours. Once removed from refrigeration, administer within 6 hours (including infusion time). Do not freeze reconstituted solution or solution diluted for infusion

Based on the mechanism of action, in utero exposure to belantamab mafodotin may cause fetal harm