1 INDICATIONS 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.

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6 ADVERSE 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 [see Clinical Studies ( 14 )] .

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 >1 patient included pneumonia (4%), sepsis (2%), COVID-19 (1%), respiratory failure (<1%), and intracranial hemorrhage (<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 <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.