4.1. Therapeutic indications

Blenrep in combination with bortezomib and dexamethasone is indicated for the treatment of adult patients with multiple myeloma who have received at least one prior therapy

Blenrep in combination with pomalidomide and dexamethasone is indicated for the treatment of adult patients with multiple myeloma who have received at least one prior therapy including lenalidomide

4.2. Posology and method of administration

Treatment with Blenrep should be initiated and monitored by physicians experienced in the treatment of multiple myeloma.

Recommended supportive care

Patients should have an ophthalmic examination (including visual acuity and slit lamp examination) performed by an eye care professional before each of the first 4 doses of Blenrep, and as clinically indicated thereafter (see section 4.4).

Physicians should encourage patients to inform them of any ocular symptoms. Additionally, physicians should advise patients to administer preservative-free artificial tears at least 4 times a day beginning on the first day of infusion and continuing until completion of treatment as this may reduce ocular symptoms (see section 4.4).

For patients with dry eye symptoms, additional therapies may be considered as recommended by their eye care professional.

Posology

Administration of Blenrep is to be continued according to the recommended schedule until disease progression or unacceptable toxicity. Blenrep is administered in combination with other treatments (see Table 1). For dosing instructions of agents administered in combination with Blenrep, see section 5.1 or refer to the corresponding Summary of Product Characteristics for the combination products, as appropriate.

Blenrep in combination with bortezomib and dexamethasone

When combined with bortezomib and dexamethasone, Blenrep is administered as a 30-minute infusion. Blenrep is administered once every 3 weeks with a starting dose of 2.5 mg/kg. Blenrep is administered from Cycle 1 until completion of treatment, while bortezomib and dexamethasone are administered for the first 8 Cycles. Each 21-day period is considered one treatment cycle.

Blenrep in combination with pomalidomide and dexamethasone

When combined with pomalidomide and dexamethasone, Blenrep is administered as a 30-minute infusion. Blenrep is administered once every 4 weeks with a starting dose of 2.5 mg/kg given once in Cycle 1. From Cycle 2 and onwards, Blenrep is dosed at 1.9 mg/kg. Each 28-day period is considered one treatment cycle.

Dose modifications

The dosage of Blenrep should be individualised for each patient. Dose reduction levels for Blenrep are provided in Tables 1 and 2. Recommended modifications to manage adverse reactions are provided in Tables 3 and 4.

Table 1: Dose reduction schedule for Blenrep in combination with bortezomib and dexamethasone (BVd) (3-week cycle dosing regimen)a

Dose Levels

Schedule

Recommended starting dose schedule

2.5 mg/kg every 3 weeks

Reduced dose level 1

1.9 mg/kg every 3 weeks

Reduced dose level 2

NA

NA = Not applicable.

a Extended dosing intervals were observed during the clinical studies (see section 5.1, Table 10).

Table 2: Dose reduction schedule for Blenrep in combination with pomalidomide and dexamethasone (BPd) (4-week cycle dosing regimen)a

Dose Levels

Schedule

Recommended starting dose schedule

2.5 mg/kg once for Cycle 1 followed by 1.9 mg/kg once every 4 weeks starting with Cycle 2

Reduced dose level 1

1.9 mg/kg every 8 weeks

Reduced dose level 2

1.4 mg/kg every 8 weeks

NA = Not applicable.

a Extended dosing intervals were observed during the clinical studies (see section 5.1, Table 12).

Management of ocular adverse reactions

Dose modifications are based on corneal examination findings and/or changes in best corrected visual acuity (BCVA) (see sections 4.4 and 4.8). The treating physician should review the patient's ophthalmic examination findings before dosing and determine the dose of Blenrep based on the highest category from the corneal examination and/or BCVA finding in the most severely affected eye as both eyes may not be affected to the same degree.

During the ophthalmic examination, the eye care professional should assess the following:

• The corneal examination finding(s) and the decline in BCVA.

• If there is a decline in BCVA, the relationship to Blenrep should be determined.

• The category grading for these examination findings and BCVA changes should be communicated to the treating physician.

The corneal examination findings may or may not be accompanied by changes in BCVA. Note: One eye may be more severely affected than the other. It is important for physicians to consider not only corneal examination findings but also visual acuity changes and reported symptoms as they evaluate dose delays and reductions.

Do not re-escalate Blenrep dose after a dose reduction is made for ocular adverse reactions.

Table 3: Recommended dose modifications for ocular adverse reactions

Severitya

Recommended dose modifications

Grade 1

Corneal examination finding(s)

Mild superficial punctate keratopathy with worsening from baseline, with or without symptoms.

Change in BCVA

Decline from baseline of 1 line on Snellen Equivalent Visual Acuity.

Continue treatment at current dose.

Grade 2

Corneal examination finding(s)

Moderate superficial punctate keratopathy, patchy microcyst-like deposits, peripheral sub-epithelial haze, or a new peripheral stromal opacity.

Change in BCVA

Decline from baseline of 2 lines (and Snellen Equivalent Visual Acuity not worse than 20/200).

Or

Grade 3

Corneal examination finding(s)

Severe superficial punctate keratopathy, diffuse microcyst-like deposits involving the central cornea, central sub-epithelial haze, or a new central stromal opacity.

Change in BCVA

Decline from baseline of 3 or more lines (and Snellen Equivalent Visual Acuity not worse than 20/200).

Withhold treatment until improvement in both corneal examination findings and BCVA to Grade 1 or better. Resume treatment at reduced dose level 1 as per Tables 1 and 2.b

Grade 4

Corneal examination finding(s)

Corneal epithelial defect.c

Or

Change in BCVA

Decline to Snellen Equivalent Visual Acuity of worse than 20/200.

Withhold until improvement in both corneal examination findings and BCVA to Grade 1 or better. Resume treatment at reduced dose level 1 for BVd and level 2 for BPd, if applicable.

For worsening symptoms that are unresponsive to dose reductions or withholding of treatment, consider permanent discontinuation.

BCVA = best corrected visual acuity; BPd = Blenrep with pomalidomide and dexamethasone; BVd = Blenrep with bortezomib and dexamethasone.

a Ocular adverse reaction severity is defined by the most severely affected eye as both eyes may not be affected to the same degree.

b If toxicity is identified prior to dosing Cycle 2 for Blenrep with pomalidomide and dexamethasone, dose at 1.9 mg/kg every 4 weeks.

c A corneal defect may lead to corneal ulcers. These should be managed promptly and as clinically indicated by an eye care professional.

Table 4: Recommended dose modifications for other adverse reactionsa

Adverse Reaction

Severity

Recommended dose modifications

Thrombocytopenia

Grade 3

No bleeding:

• For patients on 2.5 mg/kg, reduce Blenrep to 1.9 mg/kg. For patients on 1.9 mg/kg or lower, continue at same dose.b

With bleeding:

• Withhold Blenrep until improvement to Grade 2 or better. For patients previously on 2.5 mg/kg, resume Blenrep at 1.9 mg/kg. For patients on 1.9 mg/kg or lower, resume at same dose.

Consider additional supportive treatment (e.g., transfusion), as clinically indicated and per local practice.

Grade 4

Withhold the dose. Consider restarting if recovered to Grade 3 or better, and only if there is no active bleeding at time of treatment restart. For patients previously on 2.5 mg/kg, resume Blenrep at 1.9 mg/kg. For patients on 1.9 mg/kg or lower, resume at same dose.

If thrombocytopenia is considered disease-related, is not accompanied by bleeding, and recovers with transfusion to >25 x109/L, continuing treatment at the same dose may be considered.

Infusion-related reactions

Grade 2

Interrupt infusion and provide supportive treatment. Once symptoms resolve to Grade 1 or better, resume at a decreased infusion rate by at least 50% and may consider premedication.

Grade 3

Interrupt infusion and provide supportive treatment. Once symptoms resolve to Grade 1 or better, resume with premedication and at lower infusion rate extended to 2 to 4 hours. Any future infusion requires premedication.

Grade 4

Permanently discontinue Blenrep.

If anaphylactic or life-threatening infusion reaction, permanently discontinue the infusion and institute appropriate emergency care.

Other adverse reactions

Grade 3

Withhold Blenrep until improvement to Grade 1 or better. For patients previously on 2.5 mg/kg, resume Blenrep at 1.9 mg/kg. For patients on 1.9 mg/kg or lower, resume at same dose.

Grade 4

Consider permanent discontinuation of Blenrep.

If continuing treatment, withhold Blenrep until improvement to Grade 1 or better. For patients previously on 2.5 mg/kg, resume Blenrep at 1.9 mg/kg. For patients on 1.9 mg/kg or lower, resume at same dose.

a Other adverse reactions were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE).

b For Blenrep with bortezomib and dexamethasone, may consider reverting to previous dose, if appropriate once thrombocytopenia recovers to Grade 2 or better.

Special populations

Elderly

No dose adjustment is recommended for patients who are aged 65 years or over (see section 5.2).

Renal impairment

No dose adjustment is recommended in patients with mild (60≤eGFR<90 mL/min), moderate (30≤eGFR<60 mL/min), severe renal impairment (eGFR<30 mL/min not requiring dialysis), or end stage renal disease (eGFR<15 mL/min requiring dialysis) (see section 5.2).

Hepatic impairment

No dose adjustment is recommended in patients with mild hepatic impairment (total bilirubin greater than upper limit of normal [ULN] to ≤ 1.5 × ULN and any aspartate transaminase [AST] or total bilirubin ≤ ULN with AST > ULN). There are limited data in patients with moderate hepatic impairment, and therefore dosing of Blenrep in these patients should be carefully considered (see section 5.2). There are no data in patients with severe hepatic impairment.

Body weight

Blenrep is dosed based on actual body weight and has been studied in patients with body weight 37-170 kg (see section 5.2).

Paediatric population

The safety and efficacy of Blenrep in children and adolescents aged under 18 years of age have not been established. No data are available.

Method of administration

Blenrep is for intravenous use.

Blenrep must be reconstituted and diluted by a healthcare professional prior to administration as an intravenous infusion over 30 minutes.

Blenrep must not be administered as an intravenous push or bolus injection.

For instructions on dilution of the medicinal product before administration, see section 6.6.

4.3. Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4. Special warnings and precautions for use

Ocular adverse reactions

Ocular adverse reactions (e.g., blurred vision, dry eye, eye irritation, and photophobia) have been reported with the use of Blenrep (see section 4.8). The most commonly reported corneal examination findings include superficial punctuate keratopathy, microcyst-like epithelial changes, and haze, with or without changes in visual acuity. Clinically relevant changes in visual acuity may be associated with difficulty in driving or operating machinery (see section 4.7).

Ophthalmic examinations, including assessment of visual acuity and slit lamp examination, should be performed before each of the first 4 doses of Blenrep and during treatment as clinically indicated.

Patients should be advised to administer preservative-free artificial tears at least 4 times a day during treatment (see section 4.2). Patients should avoid using contact lenses until the end of treatment. Bandage contact lenses may be used under the direction of an ophthalmologist.

Patients experiencing corneal examination findings (keratopathies such as superficial punctate keratopathy or microcyst-like deposits) with or without changes in visual acuity may require a dose modification (delay and/or reduction) or treatment discontinuation based on severity of findings (see section 4.2).

Cases of corneal ulcer (ulcerative and infective keratitis) have been reported (see section 4.8). These should be managed promptly and as clinically indicated by an eye care professional. Treatment with Blenrep should be interrupted until the corneal ulcer has healed (see section 4.2).

Thrombocytopenia

Thrombocytopenic events (thrombocytopenia and platelet count decreased) have been reported with the use of Blenrep (see section 4.8). Thrombocytopenia may lead to serious bleeding events, including gastrointestinal and intracranial bleeding.

Complete blood counts are to be obtained at baseline and monitored during treatment, as clinically indicated. Patients experiencing Grade 3 or 4 thrombocytopenia or those on concomitant anticoagulant treatments may require more frequent monitoring and may be managed with a dose delay or dose reduction (see section 4.2). Supportive therapy (e.g., platelet transfusions) may be provided according to standard medical practice.

Infusion-Related Reactions

Infusion-related reactions (IRRs) have been reported with the use of Blenrep. Most IRRs were Grade 1 or 2 and resolved within the same day (see section 4.8). Patients experiencing IRR may require a dose modification (delay and/or reduction) or treatment discontinuation based on severity of findings (see section 4.2).

Pneumonitis

Cases of pneumonitis, including fatal events, have been observed with Blenrep, although a causal association has not been established. Evaluation of patients with new or worsening unexplained pulmonary symptoms (e.g., cough, dyspnoea) must be performed to exclude possible pneumonitis. In case of suspected Grade 3 or higher pneumonitis, it is recommended that Blenrep is withheld and appropriate treatment initiated (see section 4.2). Blenrep should only be resumed after an evaluation of the benefit and risk.

Hepatitis B virus reactivation

Hepatitis B virus (HBV) reactivation can occur in patients treated with medicinal products directed against B cells, including Blenrep. Patients with evidence of positive HBV serology must be monitored for clinical and laboratory signs of HBV reactivation. If reactivation of HBV occurs while on Blenrep, patients must be treated according to clinical guidelines.

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Sodium content

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e., essentially “sodium-free”.

4.5. Interaction with other medicinal products and other forms of interaction

No drug interaction studies have been performed. Based on available in vitro and clinical data, there is a low risk of pharmacokinetic or pharmacodynamic drug interactions for belantamab mafodotin. Combination therapies with bortezomib, lenalidomide, pomalidomide, and/or dexamethasone do not affect the pharmacokinetic properties of belantamab mafodotin (see section 5.2).

4.6. Fertility, pregnancy, and lactation

Women of child-bearing potential/Contraception in males and females

Women

The pregnancy status of child-bearing women must be verified prior to initiating therapy with Blenrep. Women of child-bearing potential must use effective contraception during treatment with Blenrep and for at least 4 months after the last dose.

Men

Men with female partners of child-bearing potential must use effective contraception during treatment with Blenrep and for at least 6 months after the last dose.

Pregnancy

There are no data from the use of belantamab mafodotin in pregnant women. Based on the mechanism of action of the cytotoxic component monomethyl auristatin F (MMAF), belantamab mafodotin can cause embryo-foetal harm when administered to a pregnant woman (see section 5.3). Human immunoglobulins (IgG) are known to cross the placental barrier, and therefore, being an IgG, belantamab mafodotin has the potential to be transmitted from the mother to the developing foetus.

Blenrep is not recommended during pregnancy unless the benefit to the mother outweighs the potential risks to the foetus. If a pregnant woman needs to be treated she must be clearly advised on the potential risk to the foetus.

Breast-feeding

It is unknown whether belantamab mafodotin is excreted into human milk. Immunoglobulin G (IgG) is present in human milk in small amounts. Since belantamab mafodotin is a humanised IgG monoclonal antibody, and based on the mechanism of action, it may potentially cause serious adverse reactions in breastfed children.

Breast-feeding should be discontinued prior to initiating treatment with Blenrep and for at least 3 months after the last dose of Blenrep.

Fertility

Based on findings in animals and the mechanism of action, belantamab mafodotin may impair fertility in females and males of reproductive potential (see section 5.3).

Therefore, physicians should counsel women of childbearing potential and men being treated with Blenrep regarding fertility preservation.

4.7. Effects on ability to drive and use machines

Changes in visual acuity may be associated with difficulty for driving and reading. Advise patients to use caution when driving or operating machinery.

Patients must be advised to use caution when driving or operating machines while on Blenrep as it may affect patients' vision and influence their ability to drive or use machines due to impact on visual acuity and other ocular adverse reactions (see sections 4.4 and 4.8).

4.8. Undesirable effects

Summary of the safety profile

In combination with bortezomib and dexamethasone

The safety of Blenrep has been evaluated in 242 patients who received Blenrep in combination with bortezomib and dexamethasone (BVd) in DREAMM-7. The dosing regimen was 2.5 mg/kg once every 3 weeks with individual dose modification for adverse events as needed (see sections 4.2 and 5.1). Adverse reactions leading to permanent discontinuation of any component of therapy occurred in 31% of patients and in 9% of patients were due to ocular events including ocular adverse reactions, visual acuity changes, or corneal examination findings. Adverse reactions leading to dose delays of any component of therapy occurred in 94% of patients and in 78% of patients were due to ocular events. Adverse reactions leading to dose reductions of any component of therapy occurred in 75% of patients and in 44% of patients were due to ocular events.

The most frequent adverse reactions (≥20%) in BVd included reduced visual acuity (89%), thrombocytopenia (87%), corneal examination findings (86%), blurred vision (66%), dry eye (51%), photophobia (47%), foreign body sensation in eyes (44%), eye irritation (43%), eye pain (32%), diarrhoea (32%), and upper respiratory tract infection (20%).

Serious adverse reactions of BVd occurred in 50% of patients. Serious adverse reactions in ≥2% of patients included pneumonia (11%), pyrexia (5%), thrombocytopenia (5%), and anemia (2%). Fatal adverse reactions occurred in 10% of patients and the most common was pneumonia (3%).

In combination with pomalidomide and dexamethasone

The safety of Blenrep has been evaluated in 150 patients who received Blenrep in combination with pomalidomide and dexamethasone (BPd) in DREAMM-8. The dosing regimen was 2.5 mg/kg once followed by 1.9 mg/kg every 4 weeks with individual dose modification for adverse events as needed (see sections 4.2 and 5.1). Adverse reactions leading to permanent discontinuation of any component of therapy occurred in 15% of patients and in 9% of patients were due to ocular events including ocular adverse reactions, visual acuity changes, or corneal examination findings. Adverse reactions leading to dose delays of any component of therapy occurred in 91% of patients and 83% of patients were due to ocular events. Adverse reactions leading to dose reductions of any component of therapy due to adverse reactions occurred in 61% of patients and in 59% of patients were due to ocular events.

The most frequent adverse reactions (≥20%) in BPd included reduced visual acuity (91%), corneal examination findings (87%), blurred vision (79%), neutropenia (63%), foreign body sensation in eyes (61%), dry eye (61%), thrombocytopenia (55%), eye irritation (50%), photophobia (44%), eye pain (33%), fatigue (27%), upper respiratory tract infection (27%), pneumonia (24%), anaemia (23%), and diarrhoea (23%).

Serious adverse reactions of BPd occurred in 63% of patients. Serious adverse reactions in ≥2% of patients included pneumonia (18%) and neutropenia (6%). Fatal adverse reactions occurred in 11% of patients and the most common was pneumonia (1%).

Tabulated list of adverse reactions

Adverse reactions reported in clinical trials of Blenrep in combination with either bortezomib and dexamethasone or pomalidomide and dexamethasone, and post-market settings, are listed in Tables 5 and 6 by system organ class and by frequency. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Frequencies are defined as:

Very common: ≥1/10

Common: ≥1/100 to <1/10

Uncommon: ≥1/1 000 to <1/100

Rare: ≥1/10 000 to <1/1 000

Table 5: Summary of adverse reactions with Blenrep in combination with bortezomib and dexamethasone

System organ class (SOC)

Adverse Reactionsa

Frequency

Incidence

All Grades

(%)

Grade 3+4

(%)

Eye Disorders

Visual acuity reducedb

Very common

89

57

Corneal examination findingsb

86

72

Vision blurred

66

22

Dry eye

51

7

Photophobia

47

2

Foreign body sensation in eyes

44

3

Eye irritation

43

5

Eye pain

32

<1

Visual impairment

11

5

Lacrimation increased

Common

9

<1

Diplopia

5

0

Eye pruritus

2

0

Ocular discomfort

1

0

Corneal ulcerc

Uncommon

<1

<1

Blood and Lymphatic System Disorders

Thrombocytopeniad

Very common

87

73

Anaemia

19

8

Neutropeniad

17

14

Lymphopeniad

12

8

Leukopeniad

10

5

Gastrointestinal Disorders

Diarrhea

Very common

32

4

Nausea

16

<1

Vomiting

Common

6

<1

Hepatobiliary Disorders

Porto-sinusoidal vascular disordere

Uncommon

<1

<1

Infections and Infestations

Upper respiratory tract infection

Very common

20

0

Pneumonia

18

9

Hepatitis B reactivation

Uncommon

<1

<1

General Disorders and Administration Site Conditions

Pyrexia

Very common

19

<1

Fatigue

19

4

Investigations

Increased alanine aminotransferase

Very common

19

6

Increased aspartate aminotransferase

15

1

Increased gamma glutamyltransferase

15

9

Increased creatinine phosphokinase

Common

5

2

Renal and Urinary Disorders

Albuminuriad

Common

5

<1

Injury, poisoning, and procedural complications

Infusion-related reactionsf

Common

2

0

a Adverse reactions, except ophthalmic examination findings, were graded according to CTCAE v5.0.

b Based on ophthalmic examination findings, which includes keratopathy.

c Includes infective keratitis and ulcerative keratitis

d Grouped term includes other related terms.

e Signs or symptoms may include abnormal liver function tests, portal hypertension, varices and ascites.

f Includes events determined to be related to infusion. Infusion reactions may include, but are not limited to pyrexia, chills, diarrhoea, nausea, asthenia, hypertension, lethargy, and tachycardia.

Table 6. Summary of adverse reactions with Blenrep in combination with pomalidomide and dexamethasone

System organ class (SOC)

Adverse Reactionsa

Frequency

Incidence

All Grades

(%)

Grade 3+4

(%)

Eye Disorders

Visual acuity reducedb

Very common

91

60

Corneal examination findingsb

87

62

Vision blurred

79

17

Dry eye

61

8

Foreign body sensation in eyes

61

6

Eye irritation

50

4

Photophobia

44

3

Eye pain

33

2

Visual impairment

15

10

Lacrimation increased

Common

6

<1

Diplopia

5

<1

Eye pruritus

3

<1

Corneal ulcerc

2

<1

Ocular discomfort

1

0

Blood and Lymphatic System Disorders

Neutropeniad

Very Common

63

57

Thrombocytopeniad

55

38

Anemia

23

10

Leukopeniad

Common

9

5

Lymphopeniad

8

5

Infections and Infestations

Upper respiratory tract infection

Very common

27

1

Pneumonia

24

16

Hepatitis B reactivatione

Uncommon

-

-

General Disorders and Administration Site Conditions

Fatigue

Very common

27

6

Pyrexia

19

<1

Gastrointestinal Disorders

Diarrhoea

Very common

23

1

Nausea

12

<1

Vomiting

Common

5

0

Hepatobiliary Disorders

Porto-sinusoidal vascular disorderf

Uncommon

<1

<1

Investigations

Increased alanine aminotransferase

Very common

15

1

Increased aspartate aminotransferase

10

3

Increased gamma glutamyltransferase

Common

7

1

Injury, Poisoning, and Procedural Complications

Infusion-related reactionsg

Common

7

1

Renal and Urinary Disorders

Albuminuria

Common

3

0

BCVA = best-corrected visual acuity.

a Adverse reactions, except ophthalmic examination findings, were graded according to CTCAE v5.0.

b Based on ophthalmic examination findings, which includes keratopathy.

c Includes infective keratitis and ulcerative keratitis

d Grouped term includes other related terms.

e Not observed in DREAMM-8 as of DCO 29 January 2024; frequency assigned as “uncommon” based on overall clinical assessment.

f Signs or symptoms may include abnormal liver function tests, portal hypertension, varices and ascites.

g Includes events determined to be related to infusion. Infusion reactions may include, but are not limited to pyrexia, chills, diarrhoea, nausea, asthenia, hypertension, lethargy, and tachycardia.

Description of selected adverse reactions

Ocular adverse reactions

DREAMM-7: Combination with bortezomib and dexamethasone:

In DREAMM-7 study, (combination with bortezomib and dexamethasone), the most common adverse reactions (>25%) included reduced visual acuity (89%, 57% Grade 3 and 4) and corneal examination findings (86%, 72% Grade 3 and 4) based on the ophthalmic examination findings, blurred vision (66%, 22% Grade 3 and 4), dry eye (51%, 7% Grade 3 and 4), photophobia (47%, 2% Grade 3 and 4), foreign body sensation in eyes (44%, 3% Grade 3 and 4), eye irritation (43%, 5% Grade 3 and 4), and eye pain (32%, <1% Grade 3 and 4).

Corneal examination findings (keratopathies such as superficial punctate keratopathy and microcyst-like deposits) were reported based on the ophthalmic examination findings as Grade 1 in 4% of patients, Grade 2 in 10% of patients, Grade 3 in 54% of patients, and Grade 4 in 19% of patients. Cases of corneal ulcer (ulcerative and infective keratitis) were reported with an incidence of <1% (n = 2).

In DREAMM-7, 86% (209/242) of patients reported at least 1 corneal examination finding or BCVA-related event (Grade ≥2) in the BVd arm. Of patients who experienced an event, 91% (190/209) continued treatment on or after the onset of the first event and received a median of 8 additional doses (range: 1 to 52).

Table 7 includes a summary of ocular adverse reactions, bilateral reduction in BCVA in patients with normal baseline (Snellen equivalent visual acuity 20/25 or better in at least one eye), and corneal examination findings in DREAMM-7.

Table 7: Ocular first events, median duration, and resolution in DREAMM-7

Ocular adverse reactionsa

Bilateral Reduction in BCVAb

Corneal examination findings (≥Grade 2 events)c

20/50 or worse for patients

20/200 or worse for patients

Number of patients with event (%)

191 (79)

82 (34)

5 (2)

198 (82)

Median time to first onset (days)

41

73.5

105

44

Improvement of first eventd, n (%)

NA

80 (98)

5 (100)

NA

Resolution of first evente, n (%)

84 (44)

77 (94)

4 (80)

172 (87)

Median time to resolution of first event (days)

52

64

86.5

95.5

Ongoing first evente, n (%)

107 (56)

5 (6)

1 (20)

26 (13)

Treatment ongoing, n (%)

39 (20)

–

–

3 (2)

Discontinued treatment and follow-up ongoing, n (%)

42 (22)

1 (1)

–

4 (2)

Discontinued treatment and follow-up ended, n (%)

26 (14)

4 (5)

1 (20)

19 (10)

BCVA = Best-correct visual acuity; NA = Not applicable.

a Resolution of ocular adverse reactions was defined as time to being free from any ocular adverse reactions.

b Resolution of visual acuity was defined as time to 20/25 or better in at least one eye.

c Resolution of corneal examination findings was defined as time to Grade 1 or better based on the ophthalmic examination findings.

d Improvement was defined as no longer 20/50, or 20/200, or worse in at least one eye.

e At the time of the data cut-off (2 OCT 2023).

DREAMM-8: Combination with pomalidomide and dexamethasone:

In DREAMM-8 study, (combination with pomalidomide and dexamethasone), the most common adverse reactions (>25%) included reduced visual acuity (91%, 60% Grade 3 and 4) and corneal examination findings based on the ophthalmic examination findings (87%, 62% Grade 3 and 4), blurred vision (79%, 17% Grade 3 and 4), dry eye (61%, 8% Grade 3 and 4), foreign body sensation in eyes (61%, 6% Grade 3 and 4), eye irritation (50%, 4% Grade 3 and 4), photophobia (44%, 3% Grade 3 and 4), and eye pain (33%, 2% Grade 3 and 4).

Corneal examination findings (keratopathies such as superficial punctate keratopathy and microcyst-like deposits) were reported based on the ophthalmic examination findings as Grade 1 in 7% of patients, Grade 2 in 18% of patients, Grade 3 in 56% of patients, and Grade 4 in 6% of patients. Cases of corneal ulcer (ulcerative keratitis) were reported with an incidence of 2% (n = 3).

In DREAMM-8, 87% (131/150) of patients reported at least 1 corneal examination finding or BCVA-related event (Grade ≥2) in the BPd arm. Of patients who experienced an event, 92% (120/131) continued treatment on or after the onset of the first event and received a median of 5 additional doses (range: 1 to 21).

Table 8 includes a summary of ocular adverse reactions, bilateral reduction in BCVA in patients with normal (Snellen equivalent visual acuity 20/25 or better in at least one eye) baseline, and corneal examination findings in DREAMM-8.

Table 8: Ocular first events, median duration, and resolution in DREAMM-8

Ocular adverse reactionsa

Bilateral reduction in BCVAb

Corneal examination findings (≥Grade 2 events)c

20/50 or worse for patients

20/200 or worse for patients

Number of patients with event (%)

133 (89)

51 (34)

2 (1)

120 (80)

Median time to first onset (days)

29

112

NAd

46.5

Improvement of first evente, n (%)

NA

47 (92)

2 (100)

NA

Resolution of first eventf, n (%)

105 (79)

43 (84)

1 (50)

108 (90)

Median time to resolution of first event (days)

120.5

57

NAd

92

Ongoing first eventf, n (%)

28 (21)

8 (16)

1 (50)

12 (10)

Treatment ongoing, n (%)

8 (6)

3 (6)

–

1 (<1)

Discontinued treatment and follow-up ongoing, n (%)

7 (5)

1 (2)

–

4 (3)

Discontinued treatment and follow-up ended, n (%)

13 (10)

4 (8)

1 (50)

7 (6)

BCVA = Best-correct visual acuity; NA = Not applicable.

a Resolution of ocular adverse reactions was defined as time to being free from any ocular adverse reactions.

b Resolution of visual acuity was defined as time to 20/25 or better in at least one eye.

c Resolution of corneal examination findings was defined as time to grade 1 or better based on the ophthalmic examination findings.

d In patients with 20/200 or worse, two patients were reported. The first onset was 29 and 673 days. Both events improved to better than bilateral 20/200 by the data cut-off, of which 1 event resolved after 57 days.

e Improvement was defined as no longer 20/50, or 20/200, or worse in at least one eye.

f At the time of the data cut-off (29 JAN 2024).

Infusion-related reactions

In DREAMM-7 (combination with bortezomib and dexamethasone), the incidence of IRR was 2% (n = 5). All IRRs were reported as maximum Grade 1 (<1%) and Grade 2 (1%).

In DREAMM-8 (combination with pomalidomide and dexamethasone), the incidence of IRR was 7% (n = 11). Most IRRs were reported as maximum Grade 1 (1%) and Grade 2 (5%), while 1% experienced Grade 3 IRRs. One patient discontinued treatment due to IRR.

Thrombocytopenia

In DREAMM-7 (combination with bortezomib and dexamethasone), thrombocytopenic events (thrombocytopenia and platelet count decreased) occurred in 87% of patients (n = 211). Grade 2 thrombocytopenic events occurred in 10% of patients, Grade 3 in 26%, and Grade 4 in 47%. Clinically significant bleeding (≥Grade 2) occurred in 7% of patients with concomitant low platelet levels (Grades 3 to 4).

In DREAMM-8 (combination with pomalidomide and dexamethasone), thrombocytopenic events (thrombocytopenia and platelet count decreased) occurred in 55% of patients (n = 82). Grade 2 thrombocytopenic events occurred in 11% of patients, Grade 3 in 26%, and Grade 4 in 12%. Clinically significant bleeding (≥Grade 2) occurred in 3% of patients with concomitant low platelet levels (Grades 3 to 4).

Infections

In DREAMM-7 (combination with bortezomib and dexamethasone), pneumonia was reported in 18% of patients (n = 44) with 12% reported as ≥Grade 3. Seven patients had a pneumonia event with a fatal outcome.

In DREAMM-8 (combination with pomalidomide and dexamethasone), pneumonia was reported in 24% of patients (n = 36) with 17% reported as ≥Grade 3. Two patients had a pneumonia event with a fatal outcome.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects, you can help provide more information on the safety of this medicine.

4.9. Overdose

There is no known specific antidote for belantamab mafodotin overdose. If overdose is suspected, patients must be monitored for any signs or symptoms of adverse effects and appropriate supportive treatment instituted.