Blenrep Drug Information

BLENREP is indicated in combination with bortezomib and dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least two prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent.

Important Safety Information

Ophthalmic exams, including slit lamp exam and assessment of best‑corrected visual acuity (BCVA), should be conducted by an eye care professional, such as an ophthalmologist or optometrist. Conduct ophthalmic exams at baseline, before each dose of BLENREP, promptly for new or worsening symptoms, and as clinically indicated. Counsel patients to promptly inform their healthcare provider of any ocular symptoms.

Advise patients to use preservative‑free artificial tears at least 4 times a day starting with the first infusion and continuing until end of treatment, and to avoid wearing contact lenses for the duration of therapy. Bandage contact lenses may be used under the direction of an eye care professional.

Recommended Dosage

The recommended dosage for BLENREP is 2.5 mg/kg of actual body weight once every 3 weeks in combination with bortezomib and dexamethasone (BVd) for the first 8 cycles, followed by BLENREP 2.5 mg/kg of actual body weight once every 3 weeks as a single agent until disease progression or unacceptable toxicity. For dosing instructions of agents administered in combination with BLENREP, see Clinical Studies and respective Prescribing Information, as appropriate. BLENREP is administered as an intravenous infusion over approximately 30 minutes.

Dosage Modifications for Adverse Reactions In the BVd arm of the clinical study, 98% of patients required a dosage modification for any component of treatment for an adverse reaction, including 87% who required a dosage modification of BLENREP. Eighty-three percent of patients required a dosage modification of BLENREP for ocular toxicity based on ophthalmic exam findings or other ocular adverse reactions as defined by the Common Terminology Criteria for Adverse Events (CTCAE). There were high rates of dosage modifications in early treatment cycles.

The recommended dosage modifications for ocular toxicity based on ophthalmic exam findings are provided in Tables 1 and 2. Ophthalmic exam findings include both corneal exam findings and change in BCVA as assessed by an eye care professional. The overall grade of ophthalmic exam findings is based on the worst finding in the worst affected eye, based on either corneal exam finding or a change in BCVA.

Corneal exam findings may or may not be accompanied by changes in BCVA or ocular symptoms. • Do not re‑escalate the dose of BLENREP after a dosage reduction is made for ocular toxicity based on ophthalmic exam findings. • In the clinical study, 67% of patients required a dosage interruption of BLENREP for ocular toxicity that lasted longer than 3 weeks (time between doses, median: 5.7 weeks ). The recommended dosage modifications for other adverse reactions, including dosage modifications for ocular adverse reactions based on the CTCAE, are provided in Table 3. Table 1.

Recommended Dosage Reductions of s for Ocular Toxicity Based on Ophthalmic Exam Findings a is a hazardous drug. Follow applicable special handling and disposal procedures. 1 Calculate the dose (mg), total volume (mL) of solution required, and the number of vials of BLENREP needed based on the patient’s actual body weight. More than one vial may be needed for a full dose.

Reconstitution • Remove the vial(s) of BLENREP from the refrigerator and allow to stand for approximately 10 minutes to reach room temperature (68°F to 77°F ). • Reconstitute each 70 mg vial of BLENREP with 1.4 mL of Sterile Water for Injection, USP, to obtain a final concentration of 50 mg/mL. Gently swirl the vial to aid dissolution. Do not shake. • If the reconstituted solution is not used immediately, store in the original container refrigerated at 36ºF to 46ºF (2ºC to 8ºC) or at room temperature (68°F to 77°F ) for up to 4 hours.

Discard if not diluted within 4 hours. Do not freeze. • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The reconstituted solution should be a clear to opalescent, colorless to yellow to brown liquid.

Discard if extraneous particulate matter is observed. Dilution • Withdraw the calculated volume of BLENREP from the appropriate number of vials and dilute in a 250 mL infusion bag of 0.9% Sodium Chloride Injection, USP, to a final concentration of 0.2 mg/mL to 2 mg/mL. The infusion bag must be made of polyvinylchloride (PVC) or polyolefin (PO). • Mix the diluted solution by gentle inversion.

Do not shake. • Discard any unused reconstituted solution of BLENREP left in the vial(s). • If the diluted infusion solution is not used immediately, store refrigerated at 36ºF to 46ºF (2ºC to 8ºC) for up to 24 hours. Do not freeze. Once removed from refrigeration, administer the diluted infusion solution of BLENREP within 6 hours (including infusion time). • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

The diluted infusion solution should be clear and colorless. Administration • If refrigerated, allow the diluted infusion solution to equilibrate to room temperature (68ºF to 77ºF ) prior to administration. Diluted infusion solution may be kept at room temperature for no more than 6 hours (including infusion time). • Administer by intravenous infusion over approximately 30 minutes using an infusion set made of PVC or PO. • Filtration of the diluted solution is not required; however, if the diluted solution is filtered, use a polyethersulfone (PES)-based filter (0.2 micron).

Do not mix or administer BLENREP with other products. The product does not contain a preservative.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. Relapsed or Refractory Multiple Myeloma in Combination with Bortezomib and Dexamethasone The safety of BLENREP with bortezomib and dexamethasone (n = 242) compared with daratumumab with bortezomib and dexamethasone (n = 246) was evaluated in DREAMM‑7 in patients with relapsed or refractory multiple myeloma who received at least one prior line of therapy. Patients received BLENREP 2.5 mg/kg of actual body weight once every 3 weeks in combination with bortezomib and dexamethasone (BVd) for the first 8 cycles, followed by BLENREP as a single agent or daratumumab in combination with bortezomib and dexamethasone (DVd) for the first 8 cycles, followed by daratumumab as a single agent.

Among patients who received BLENREP, 69% were exposed for 6 months or longer and 55% were exposed for greater than one year. The safety of BLENREP in combination with bortezomib and dexamethasone in patients who received only one prior line of therapy (n = 125) has not been established. Serious adverse reactions occurred in 50% of patients who received BVd.

Fatal adverse reactions occurred in 10% of patients who received BVd. Permanent discontinuation of BLENREP due to an adverse reaction occurred in 17% of patients. Adverse reactions which resulted in permanent discontinuation of BLENREP in ≥3% of patients included ocular toxicity (9%) and pneumonia (4%).

Dosage interruptions of BLENREP due to an adverse reaction occurred in 78% of patients. Dosage reductions of BLENREP due to an adverse reaction occurred in 36% of patients. The most common adverse reactions (≥20%) were reduction in BCVA, corneal exam findings, blurred vision, dry eye, photophobia, foreign body sensation in eyes, eye irritation, upper respiratory tract infection, hepatotoxicity, eye pain, diarrhea, fatigue, pneumonia, cataract, and COVID-19.

The most common Grade 3 or 4 laboratory abnormalities (≥10%) were decreased platelets, decreased lymphocytes, decreased neutrophils, increased gamma glutamyltransferase, decreased white blood cells, and decreased hemoglobin. Table 4 summarizes the adverse reactions in DREAMM‑7. Table 4.

Adverse Reactions (≥10%) in Patients with Relapsed or Refractory Multiple Myeloma Who Received BLENREP in DREAMM-7 2 Clinically relevant adverse reactions in <10% of patients who received BVd included: increased lacrimation, vomiting, diplopia, albuminuria, sepsis, eye pruritus, infusion-related reactions, corneal ulcer (including cases with infection), and pneumonitis. Table 5 summarizes the laboratory abnormalities in DREAMM-7. Table 5.

Select Laboratory Abnormalities (>10%) That Worsened from Baseline in Patients with Relapsed or Refractory Multiple Myeloma Who Received BLENREP in DREAMM-7 3 Patient-reported ocular symptoms were assessed using the Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE) and Ocular Surface Disease Index (OSDI). PRO-CTCAE assessments were collected at baseline and then every 3 weeks until treatment discontinuation. Completion rates in both arms were ≥90% at baseline and ≥81% at subsequent timepoints where >50% of patients remained on treatment.

Table 6 summarizes the patient-reported symptom of blurred vision as assessed by PRO-CTCAE. Table 6. Patient-Reported Symptom of Blurred Vision Assessed by PRO-CTCAE in Patients with Relapsed or Refractory Multiple Myeloma in DREAMM-7 Driving at night was assessed using the OSDI.

At baseline, the proportion of patients who reported limitations with driving at night “all of the time” or “most of the time” during the last week was 9% in the BVd arm and 4% in the DVd arm. The proportion of patients who reported limitations with driving at night “all of the time” or “most of the time” during the last week was highest in the BVd arm at 47% at Week 13 and in the DVd arm at 12% at Week 76.

Pregnancy Risk Summary Based on its mechanism of action, BLENREP can cause fetal harm when administered to a pregnant woman, because it contains a genotoxic compound (the microtubule inhibitor, MMAF) and it targets actively dividing cells. Human immunoglobulin G (IgG) is known to cross the placenta; therefore, belantamab mafodotin-blmf has the potential to be transmitted from the mother to the developing fetus. There are no available data on the use of BLENREP in pregnant women to evaluate for drug-associated risk.

No animal reproduction studies were conducted with BLENREP. Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively.

Data Animal Data: Animal reproductive or developmental toxicity studies were not conducted with belantamab mafodotin‑blmf. The cytotoxic component of BLENREP, mcMMAF, disrupts microtubule function, is genotoxic, and can be toxic to rapidly dividing cells, suggesting it has the potential to cause embryo‑fetal toxicity.

Pediatric Use The safety and effectiveness of BLENREP in pediatric patients have not been established.