BELANTAMAB MAFODOTIN: 2,293 Adverse Event Reports & Safety Profile

Belantamab mafodotin‑blmf is a B‑cell maturation antigen (BCMA)‑directed antibody and microtubule inhibitor conjugate. Belantamab mafodotin‑blmf is an antibody conjugate composed of 3 components: 1) afucosylated, humanized immunoglobulin G1 monoclonal antibody covalently linked to 2) the microtubule inhibitor mcMMAF via 3) a protease‑resistant maleimidocaproyl linker. The antibody is produced in a mammalian cell line (Chinese Hamster Ovary) using recombinant DNA technology and the microtubule inhibitor and linker are produced by chemical synthesis.

Approximately

4 molecules of mafodotin are attached to each antibody molecule. The molecular weight of belantamab mafodotin‑blmf is approximately 152 kDa. Belantamab mafodotin‑blmf has the following structure: BLENREP (belantamab mafodotin‑blmf) for injection is a sterile, preservative‑free, white to yellow, lyophilized powder in a single‑dose vial for reconstitution and further dilution prior to intravenous use. BLENREP is supplied as 70 mg per vial and requires reconstitution with 1.4 mL of Sterile Water for Injection, USP, to obtain a concentration of 50 mg/mL. Each mL of reconstituted solution contains belantamab mafodotin‑blmf (50 mg) and the inactive ingredients, citric acid monohydrate (0.46 mg), edetate disodium (0.017 mg), polysorbate 80 (0.2 mg), sodium citrate (5.88 mg), and trehalose (68.4 mg). The pH of the reconstituted solution is 6.2. Belantamab mafodotin-blmf chemical structure

AND USAGE 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. BLENREP, a B‑cell maturation antigen (BCMA)‑directed antibody and microtubule inhibitor conjugate, 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. ( 1 )

AND ADMINISTRATION

• The recommended dosage of BLENREP, in combination with bortezomib and dexamethasone, is 2.5 mg/kg as an intravenous infusion over 30 minutes once every 3 weeks for 8 cycles, followed by BLENREP 2.5 mg/kg every 3 weeks as a single agent. ( 2.2 )
• See Full Prescribing Information for instructions on preparation and administration. ( 2.4 )

2.1 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 <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.1 )]</span>. 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 <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.1 )]</span>.

2.2 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 ( 14 ) and respective Prescribing Information, as appropriate. BLENREP is administered as an intravenous infusion over approximately 30 minutes.

2.3 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 <span class="opacity-50 text-xs">[see Clinical Studies ( 14 )]</span> . 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) <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span> . There were high rates of dosage modifications in early treatment cycles.

By Cycle

3, 53% of patients had a dosage interruption or reduction, 7% had discontinued treatment, and only 40% received the planned dose of BLENREP. 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 [range: 3 to 31 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 BLENREP for Adverse Reactions a Reduced Dosage Level 2 is specific to dosage reductions due to ocular toxicity based on ophthalmic exam findings.

Blenrep

Reduced Dosage Level 1 1.9 mg/kg every 3 weeks Reduced Dosage Level 2 a 1.9 mg/kg every 8 weeks Table 2.

Recommended Dosage

Modifications for Ocular Toxicity Based on Ophthalmic Exam Findings a BCVA = best‑corrected visual acuity. a Mild superficial keratopathy (documented worsening from baseline). Refer to Table 3 for recommended dosage modifications for other ocular adverse reactions. b Microcyst‑like deposits are considered at least a Grade 2 finding. Withhold BLENREP if any microcyst‑like deposits are observed.

Severity Ophthalmic Exam

Findings [see Warnings and Precautions ( 5.1 )]

Recommended Dosage Modification Grade

1 Corneal Exam Findings: Mild superficial punctate keratopathy a and/or Change in BCVA: Decline from baseline of 1 line on Snellen Equivalent BCVA Continue treatment at current dosage.

Grade

2 Corneal Exam Findings: Moderate superficial punctate keratopathy, patchy microcyst‑like deposits b , peripheral sub‑epithelial haze, or a new peripheral stromal opacity and/or Change in BCVA: Decline from baseline of 2 lines on Snellen Equivalent BCVA and not worse than 20/200 Withhold BLENREP until improvement in both corneal exam findings and change in BCVA to Grade 1 or less. Resume treatment at Reduced Dosage Level 1 as per Table 1 . If recurrent Grade 2 or 3 ocular toxicity is experienced, resume treatment at Reduced Dosage Level 2.

Grade

3 Corneal Exam Findings: Severe superficial punctate keratopathy, diffuse microcyst‑like deposits b involving the central cornea, central sub‑epithelial haze, or a new central stromal opacity and/or Change in BCVA: Decline from baseline of 3 or more lines on Snellen Equivalent BCVA and not worse than 20/200 Grade 4 Corneal Exam Findings: Corneal epithelial defect or corneal ulcer, with or without infection and/or Change in BCVA: Decline to Snellen Equivalent BCVA of worse than 20/200 Consider permanent discontinuation of BLENREP. If continuing treatment, withhold BLENREP until improvement in both corneal exam findings and change in BCVA to Grade 1 or less. For patients previously on 2.5 mg/kg every 3 weeks, resume treatment at Reduced Dosage Level 1 as per Table 1 . For patients previously on 1.9 mg/kg every 3 weeks, resume treatment at Reduced Dosage Level 2. If recurrent Grade 4 ocular toxicity is experienced, permanently discontinue BLENREP.

Table

3.

Recommended Dosage

Modifications for Other Adverse Reactions a a Adverse reactions were graded according to the Common Terminology Criteria for Adverse Events v5.0. b Consider reverting to previous dose, if appropriate once platelet count recovers to 50,000/mcL or higher.

Adverse Reaction Severity Recommended Dosage

Modification Thrombocytopenia [see Warnings and Precautions ( 5.3 )] Platelet count between 25,000/mcL and 50,000/mcL without bleeding For patients on 2.5 mg/kg, reduce to Reduced Dosage Level 1 as per Table 1 . b For patients on 1.9 mg/kg, continue at same dosage. Platelet count between 25,000/mcL and 50,000/mcL with bleeding Withhold BLENREP until bleeding resolves. For patients previously on 2.5 mg/kg, resume at Reduced Dosage Level 1 as per Table 1 . For patients on 1.9 mg/kg, resume at same dosage. Platelet count less than 25,000/mcL Withhold BLENREP until platelet count recovers to 25,000/mcL or higher. For patients previously on 2.5 mg/kg, resume at Reduced Dosage Level 1 as per Table 1 . For patients on 1.9 mg/kg, resume at same dosage. Infusion-related Reactions Grade 2 Interrupt infusion and provide supportive care. Once symptoms resolve to Grade 1 or less, resume infusion at 50% of the initial rate prior to the event. Consider premedication for subsequent infusions.

Grade

3 Interrupt infusion and provide supportive care. Once symptoms resolve to Grade 1 or less, resume at 50% of the initial rate prior to the event. Administer premedication for subsequent infusions.

Grade

4 Permanently discontinue BLENREP. If anaphylactic or life‑threatening infusion reaction, permanently discontinue the infusion and institute appropriate emergency care.

Other Adverse

Reactions [see Adverse Reactions ( 6.1 ]

Grade

3 Withhold BLENREP until adverse reaction improves to Grade 1 or less. For patients previously on 2.5 mg/kg, resume at Reduced Dosage Level 1 as per Table 1 . For patients on 1.9 mg/kg, resume at same dosage.

Grade

4 Consider permanent discontinuation of BLENREP. If continuing treatment, withhold BLENREP until adverse reaction improves to Grade 1 or less. For patients previously on 2.5 mg/kg, resume at Reduced Dosage Level 1 as per Table 1 . For patients on 1.9 mg/kg, resume at same dosage.

2.4 Preparation and Administration BLENREP 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 [20°C to 25°C]).
• 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 [20°C to 25°C]) 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. Discard if particulate matter is observed. Administration
• If refrigerated, allow the diluted infusion solution to equilibrate to room temperature (68ºF to 77ºF [20ºC to 25ºC]) 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.

None. None. ( 4 )

REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling:

• Ocular Toxicity [see Warnings and Precautions ( 5.1 )]
• Thrombocytopenia [see Warnings and Precautions ( 5.3 )] The most common adverse reactions (≥20%) with BLENREP in combination with bortezomib and dexamethasone are reduction in best-corrected visual acuity (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 (≥10%) laboratory abnormalities are decreased platelets, decreased lymphocytes, decreased neutrophils, increased gamma-glutamyl transferase, decreased white blood cells, and decreased hemoglobin. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact GlaxoSmithKline at 1-888-825-5249 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1 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 <span class="opacity-50 text-xs">[see Clinical Studies ( 14 )]</span> . 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. Serious adverse reactions in ≥2% of patients included pneumonia (18%), pyrexia (5%), thrombocytopenia (5%), COVID-19 (5%), upper respiratory tract infection (4%), sepsis (4%), second primary malignancy (3%), and anemia (2%). Fatal adverse reactions occurred in 10% of patients who received BVd. Fatal adverse reactions which occurred in &gt;1 patient included pneumonia (4%), sepsis (2%), COVID-19 (1%), respiratory failure (&lt;1%), and intracranial hemorrhage (&lt;1%). 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. Adverse reactions which required dosage interruption of BLENREP in ≥3% of patients included ocular toxicity based on ophthalmic exam findings (74%), blurred vision (32%), upper respiratory tract infection (20%), dry eye (14%), photophobia (14%), pneumonia (14%), eye irritation (13%), COVID-19 (12%), foreign body sensation in eyes (12%), eye pain (10%), thrombocytopenia (9%), visual impairment (7%), cataract (5%), diarrhea (4%), and neutropenia (4%). Dosage reductions of BLENREP due to an adverse reaction occurred in 36% of patients. Adverse reactions which required dosage reductions for BLENREP in ≥3% of patients included ocular toxicity based on ophthalmic exam findings (30%), thrombocytopenia (14%), and blurred vision (10%). 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 BCVA = best‑corrected visual acuity; BVd = BLENREP + bortezomib and dexamethasone; DVd = daratumumab + bortezomib and dexamethasone. a Adverse reactions, except ophthalmic exam findings, were graded according to Common Terminology Criteria for Adverse Events v5.0. b Based on ophthalmic exam findings. c Grouped term includes other related terms. d Includes the following fatal adverse reactions: BVd: pneumonia (n = 10), COVID-19 (n = 3), upper respiratory tract infection (n = 1); DVd: pneumonia (n = 7), COVID-19 (n = 5), pyrexia (n = 1).

Adverse

Reaction a BLENREP + Bortezomib and Dexamethasone N = 242 Daratumumab + Bortezomib and Dexamethasone N = 246 All Grades (%)

Grades

3‑4 (%)

All

Grades (%)

Grades

3‑4 (%) Eye disorders Reduction in BCVA b 89 57 44 9 Corneal exam findings b 86 72 19 3 Blurred vision 66 22 11

0.8 Dry eye c 51 7 7 0 Photophobia 47 2 2 0 Foreign body sensation in eyes c 44 3 4 0 Eye irritation 43 5 5 0 Eye pain c 33 0.8 4

0.4 Cataract c 24 8 14 3 Visual impairment 11 5 2

0.4 Gastrointestinal disorders Diarrhea 32 4 31 4 Nausea 16 0.8 12 0 Infections Upper respiratory tract infection c,d 38 2 36 2 Pneumonia c,d 26 16 17 5 COVID-19 d 24 5 20 2 Hepatobiliary disorders Hepatotoxicity c 33 14 16 2 General disorders and administration site conditions Fatigue c 26 6 27 4 Pyrexia c,d 19 0.4 11 2 Clinically relevant adverse reactions in &lt;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 Laboratory Abnormality BLENREP + Bortezomib and Dexamethasone a Daratumumab + Bortezomib and Dexamethasone a All Grades (%)

Grades

3‑4 (%)

All

Grades (%)

Grades

3‑4 (%) BVd = BLENREP + bortezomib and dexamethasone; DVd = daratumumab + bortezomib and dexamethasone. a The denominator used to calculate the rate varied from 238 to 241 (BVd) and 243 to 246 (DVd) based on the number of patients with a baseline value and at least one post-treatment value.

Hematology

Platelets decreased 100 74 88 48 Lymphocytes decreased 90 53 92 56 Leukocytes decreased 59 11 67 17 Neutrophils decreased 52 17 53 13 Hemoglobin decreased 51 10 60 12 Chemistry Aspartate aminotransferase increased 88 5 40 0 Gamma glutamyltransferase increased 73 15 44 3 Alanine aminotransferase increased 71 5 54 1 Creatinine increased 51 2 53 <1 Creatine phosphokinase increased 48 3 31 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. OSDI assessments were collected every 3 weeks until the 6 th dose and then every 6 weeks thereafter until treatment discontinuation for BVd and every 3 weeks until Cycle 6 and then every 12 weeks thereafter until treatment discontinuation for DVd. Completion rates in both arms were ≥90% at baseline and ≥52% 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 Symptom (Attribute) a Any Symptom Before Treatment b Score 3 or 4 Before Treatment c Any Symptom on Treatment d,e Score 3 or 4 on Treatment d,f BVd (%) n = 232 DVd (%) n = 227 BVd (%) n = 232 DVd (%) n = 227 BVd (%) n = 238 DVd (%) n = 239 BVd (%) n = 238 DVd (%) n = 239 BVd = BLENREP + bortezomib and dexamethasone; DVd = daratumumab + bortezomib and dexamethasone; PRO-CTCAE = patient-reported outcomes common terminology criteria for adverse events. a Symptom attribute scoring defined as severity with a score of 0 = ‘none’; 1 = ‘mild’; 2 = ‘moderate’; 3 = ‘severe’; 4 = ‘very severe’. b Percentage of patients whose symptom score before treatment was 1 to 4. c Percentage of patients whose symptom score before treatment was 3 or 4. d Number of patients who provided at least one on-treatment score. e Percentage of patients whose maximum post-baseline score was 1 to 4 on treatment. f Percentage of patients whose maximum post-baseline score was 3 or 4 on treatment. Blurred vision (severity) 28 24 <1 2 93 74 55 15 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.

AND PRECAUTIONS

• Thrombocytopenia: Monitor complete blood counts at baseline and periodically during treatment. Withhold or reduce the dosage based on severity. ( 2.3 , 5.3 )
• Embryo‑fetal Toxicity: Can cause fetal harm. Advise patients of the potential risk to fetus and to use effective contraception. ( 5.4 , 8.1 , 8.3 )

5.1 Ocular Toxicity BLENREP causes ocular toxicity, defined as changes in the corneal epithelium and changes in BCVA based on ophthalmic exam (including slit lamp exam), or other ocular adverse reactions as defined by the CTCAE <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span> . In DREAMM-7, ocular toxicity occurred in 92% of patients, including Grade 3 or 4 in 77% of patients. The most common ocular toxicities (&gt;25%) were reduction in BCVA (89%) and corneal exam findings (86%) based on ophthalmic exam findings, blurred vision (66%), dry eye (51%), photophobia (47%), foreign body sensation in eyes (44%), eye irritation (43%), and eye pain (33%) <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span> . Ocular toxicity based on ophthalmic exam findings was reported as Grade 2 in 9% of patients, Grade 3 in 56% of patients, and Grade 4 in 21% of patients. The median time to onset of the first Grade 2 to 4 ophthalmic exam findings was 43 days (range: 15 to 611 days). The median duration of all Grade 2 to 4 ophthalmic exam findings was 85 days (range: 5 to 813 days). Patients experienced a median of 3 episodes (range: 1 to 11 episodes) of ocular toxicity based on ophthalmic exam findings. Of the patients with Grade 2 to 4 ophthalmic exam findings, 42% had improvement of the last event to Grade 1 or better; 22% had resolution of the last event based on return to baseline or normal ophthalmic exam findings. The most commonly reported corneal exam findings included superficial punctate keratopathy, microcyst-like deposits, epithelial changes, and haze. Cases of corneal ulcer, including cases with infection, have been reported and should be managed promptly by an eye care professional <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span> . A reduction in BCVA to 20/50 or worse in at least one eye occurred in 69% of patients, including 29% who experienced a change in BCVA to 20/100 or worse, and 12% who experienced a change in BCVA to 20/200 or worse. Of the patients with reduced BCVA to 20/50 or worse in at least one eye, 61% had resolution of the last event to baseline or better. Of the patients with reduced BCVA to 20/100 or worse, 57% had resolution of the last event. Of the patients with reduced BCVA to 20/200 or worse, 48% had resolution of the last event. Ophthalmic exams (including slit lamp exam and BCVA assessment) should be conducted by an eye care professional, such as an ophthalmologist or optometrist, at baseline, before each dose of BLENREP, promptly for new or worsening symptoms, and as clinically indicated. Perform baseline exam within 4 weeks prior to the first dose. Perform each follow-up exam within 10 days prior to the next planned dose. All effort should be made to schedule the exam as close to BLENREP dosing as possible. Withhold BLENREP until improvement in both corneal exam findings and change in BCVA to Grade 1 or less and resume at same or reduced dose or permanently discontinue based on severity <span class="opacity-50 text-xs">[see Dosage and Administration ( 2.1 , 2.3 )]</span>. Counsel patients to promptly inform their healthcare provider of any ocular symptoms. Counsel patients to use preservative‑free artificial tears at least 4 times a day starting with the first infusion and continuing until the 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 <span class="opacity-50 text-xs">[see Dosage and Administration ( 2.1 )]</span>. Changes in visual acuity may be associated with difficulty for driving and reading. Counsel patients to use caution when driving or operating machinery. BLENREP is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.2 )]</span> .

5.2 BLENREP Risk Evaluation and Mitigation Strategy (REMS) BLENREP is available only through a restricted program called the BLENREP REMS because of the risk of ocular toxicity <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.1 )]</span>. Notable requirements of the BLENREP REMS include the following:

• Prescribers must be certified in the BLENREP REMS by enrolling and completing training.
• Prescribers must counsel patients receiving BLENREP on the risk of ocular toxicity, the need for monitoring via ophthalmic exams before each dose, and provide patients with the BLENREP REMS Patient Guide.
• Patients must be enrolled in the BLENREP REMS and adhere to monitoring.
• Healthcare settings that dispense BLENREP must be certified in the BLENREP REMS by enrolling and must obtain authorization prior to dispensing.
• Wholesalers and distributors must distribute BLENREP only to certified healthcare settings. Further information is available at www.BLENREPREMS.com and 1‑855‑690-9572.

5.3 Thrombocytopenia Thrombocytopenia of any grade occurred in 100% of patients in DREAMM‑7 <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span> .

Grade

2 thrombocytopenia occurred in 10% of patients, Grade 3 in 29% of patients, and Grade 4 in 45% of patients. Clinically significant bleeding (Grade ≥2) occurred in 7% of patients with concomitant low platelet levels (Grade 3 or 4). Monitor complete blood cell counts at baseline and periodically during treatment as clinically indicated. Withhold or reduce the dose of BLENREP based on severity [see Dosage and Administration ( 2.3 )].

5.4 Embryo-fetal Toxicity 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, monomethyl auristatin F [MMAF]) and it targets actively dividing cells. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with BLENREP and for 4 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with BLENREP and for 6 months after the last dose <span class="opacity-50 text-xs">[see Use in Specific Populations ( 8.1 , 8.3 )]</span> .