Blenrep

1 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 

 

 

 

 



 

2 

This medicinal product is subject to additional monitoring. This will allow quick identification of 

new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 

See section 4.8 for how to report adverse reactions. 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

BLENREP 100 mg powder for concentrate for solution for infusion 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

One vial of powder contains 100 mg of belantamab mafodotin.  

 

After reconstitution, the solution contains 50 mg belantamab mafodotin per mL. 

 

Belantamab mafodotin is an antibody-drug conjugate that contains belantamab, an afucosylated 

humanised monoclonal IgG1k antibody specific for B cell maturation antigen (BCMA), produced 

using recombinant DNA technology in a mammalian cell line (Chinese Hamster Ovary) that is 

conjugated with maleimidocaproyl monomethyl auristatin F (mcMMAF). 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Powder for concentrate for solution for infusion (powder for concentrate). 

 

Lyophilised white to yellow powder. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

BLENREP is indicated as monotherapy for the treatment of multiple myeloma in adult patients, who 

have received at least four prior therapies and whose disease is refractory to at least one proteasome 

inhibitor, one immunomodulatory agent, and an anti-CD38 monoclonal antibody, and who have 

demonstrated disease progression on the last therapy. 

 

4.2 Posology and method of administration 

 

Treatment with BLENREP should be initiated and supervised 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 at baseline, before the subsequent 3 treatment cycles, and as 

clinically indicated whilst on treatment (see section 4.4).  

 

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 

corneal symptoms (see section 4.4).  

 

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

eye care professional.  



 

3 

 

Posology 

 

The recommended dose is 2.5 mg/kg of BLENREP administered as an intravenous infusion once 

every 3 weeks.  

 

It is recommended that treatment should be continued until disease progression or unacceptable 

toxicity (see section 4.4). 

 

Dose modifications 

 

Recommended dose modifications for corneal adverse reactions are provided in Table 1. Table 2 

provides dose modifications recommended for other adverse reactions. 

 

Management of corneal adverse reactions 

 

Corneal adverse reactions may include findings upon eye examination and/or changes in visual acuity 

(see sections 4.4 and 4.8). The treating physician should review the patient’s ophthalmic examination 

report before dosing and should determine the dose of BLENREP based on the highest category from 

the report in the most severely affected eye as both eyes may not be affected to the same degree (Table 

1). 

 

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

 

• The corneal examination finding(s) and the decline in best corrected visual acuity (BCVA). 

• If there is a decline in BCVA, the relationship of corneal examination findings to BLENREP 

should be determined. 

• The highest category grading for these examination findings and BCVA should be reported to the 

treating physician. 

 

Table 1. Dose modifications for corneal adverse reactions 

Categorya 

 

Eye examination findings 

 

Recommended dose 

modifications 

Mild Corneal examination finding(s) 

Mild superficial keratopathyb 

Change in BCVAc 

Decline from baseline of 1 line on Snellen 

Visual Acuity 

Continue treatment at current dose. 

Moderate 

 

Corneal examination finding(s) 

Moderate superficial keratopathyc 

Change in BCVA 

Decline from baseline of 2 or 3 lines (and 

Snellen Visual Acuity not worse than 

20/200) 

Withhold treatment until 

improvement in examination 

findings and BCVA to mild 

severity or better.  

Consider resuming treatment at a 

reduced dose of 1.9 mg/kg. 

Severe 

 

Corneal examination finding(s) 

Severe superficial keratopathyd 

Corneal epithelial defecte 

Change in BCVA 

Decline from baseline of more than 3 lines 

Withhold until improvement in 

examination findings and BCVA to 

mild severity or better.  

For worsening symptoms that are 

unresponsive to appropriate 

management, consider 

discontinuation. 



 

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a The severity category is defined by the most severely affected eye as both eyes may not be affected 

to the same degree. 

 b Mild superficial keratopathy (documented worsening from baseline), with or without symptoms. 
c Moderate superficial keratopathy – with or without patchy microcyst-like deposits, sub-epithelial 

haze (peripheral), or a new peripheral stromal opacity. 
d Severe superficial keratopathy with or without diffuse microcyst-like deposits involving the central 

cornea, sub-epithelial haze (central), or a new central stromal opacity. 
e A corneal defect may lead to corneal ulcers. These should be managed promptly and as clinically 

indicated by an eye care professional. 

 

Table 2. Dose modifications for other adverse reactions 

Adverse reaction  Severity  Recommended dose modifications  
Thrombocytopenia 

(see section 4.4) 

Grade 2-3:  

Platelet count 25,000 

to less than 

75,000/microlitres 

Consider withholding BLENREP and/or 

reducing the dose of BLENREP to 1.9 mg/kg. 

Grade 4: 

Platelet count less 

than 

25,000/microlitres 

Withhold BLENREP until platelet count 

improves to Grade 3 or better. Consider 

resuming at a reduced dose of 1.9 mg/kg. 

Infusion-related reactions 

(see section 4.4) 

Grade 2 

(moderate) 

Interrupt infusion and provide supportive 

treatment. Once symptoms resolve, resume at 

lower infusion rate by at least 50%. 

Grade 3 or 4 

(severe) 

Interrupt infusion and provide supportive 

treatment. Once symptoms resolve, resume at 

lower infusion rate reduced by at least 50%. If 

anaphylactic or life-threatening infusion 

reaction, permanently discontinue the infusion 

and institute appropriate emergency care. 

Adverse reactions were graded according to the National Cancer Institute Common Terminology 

Criteria for Adverse Events (CTCAE). 

 

Special populations  

 

Elderly 

No dose adjustment is required for elderly patients (see section 5.2). 

 

Renal impairment 

No dose adjustment is required in patients with mild or moderate renal impairment (eGFR 30 

mL/min). There are insufficient data in patients with severe renal impairment to support a dose 

recommendation (see section 5.2). 

 

Hepatic impairment 

No dose adjustment is required in patients with mild hepatic impairment (bilirubin greater than ULN 

to less than or equal to 1.5 × ULN or aspartate transaminase [AST] greater than ULN). There are 

insufficient data in patients with moderate hepatic impairment and no data in patients with severe 

hepatic impairment to support a dose recommendation (see section 5.2). 

 

Body weight 

BLENREP has not been studied in patients with body weight < 40 kg or > 130 kg (see section 5.2). 

 

Paediatric population 

The safety and efficacy of BLENREP in children and adolescents below 18 years of age have not been 

established. No data are available. 

 



 

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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. BLENREP should be infused over a minimum of 30 minutes (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 

 

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. 

 

Corneal adverse reactions 

 

Corneal adverse reactions have been reported with the use of BLENREP. The most commonly 

reported adverse reactions were keratopathy or microcyst-like epithelial changes in corneal epithelium 

(as seen on eye examination) with or without changes in visual acuity, blurred vision, and dry eye 

symptoms. Patients with a history of dry eyes were more prone to develop changes in the corneal 

epithelium. 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 at baseline, before the subsequent 3 treatment cycles 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. 

 

Patients experiencing keratopathy 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 

Table 1). 

 

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 Table 1). 

 

Thrombocytopenia 

 

Thrombocytopenic events (thrombocytopenia and platelet count decreased) were frequently reported 

in study 205678.  Thrombocytopenia may lead to serious bleeding events, including gastrointestinal 

and intracranial bleeding. 

 

Complete blood counts should 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 should be managed with a dose delay or dose 

reduction (see Table 2). Supportive therapy (e.g. platelet transfusions) should be provided according to 

standard medical practice. 

 

Infusion-Related Reactions 

 

Infusion-related reactions (IRR) have been reported with BLENREP. Most IRRs were Grade 1-2 and 

resolved within the same day (see section 4.8). If a grade 2 or higher infusion- related reaction occurs 

during administration, reduce the infusion rate or stop the infusion depending on the severity of the 



 

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symptoms. Institute appropriate medical treatment and restart infusion at a slower rate, if the patient’s 

condition is stable. If Grade 2 or higher IRR occurs, administer premedication for subsequent 

infusions (see Table 2). 

 

Excipients 

 

This medicinal product contains less than 1 mmol sodium (23 mg) per 100 mg dose, that is to say 

essentially “sodium-free”. 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

No formal drug interaction studies have been performed with belantamab mafodotin. 

Based on available in vitro and clinical data, there is a low risk of pharmacokinetic or 

pharmacodynamic drug interactions for 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 should be verified prior to initiating therapy with 

BLENREP. 

 

Women of child-bearing potential should use effective contraception during treatment with BLENREP 

and for 4 months after the last dose. 

 

Men 

Men with female partners of child-bearing potential should use effective contraception during 

treatment with BLENREP and for 6 months after the last dose. 

 

Pregnancy 

 

There are no data from the use of BLENREP 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 immunoglobulin G (IgG) is known to cross the placenta; therefore, belantamab 

mafodotin has the potential to be transmitted from the mother to the developing foetus (see section 

5.3). 

 

BLENREP should not be used during pregnancy unless the benefit to the mother outweighs the 

potential risks to the foetus. If a pregnant woman needs to be treated she should be clearly advised on 

the potential risk to the foetus. 

 

Breast-feeding 

 

It is not known 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 cause serious adverse reactions in 

breast-fed children. Women should be advised to discontinue breast-feeding prior to initiating 

treatment with BLENREP and for 3 months after the last dose. 

 

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). 

 



 

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Therefore, women of childbearing potential who may desire children in the future should be 

counselled prior to therapy regarding the option of having eggs frozen before treatment. Men being 

treated with this medicine are advised to have sperm samples frozen and stored before treatment.  

 

4.7 Effects on ability to drive and use machines 

 

BLENREP has a moderate influence on the ability to drive or use machines (see sections 4.4 and 4.8). 

Patients should be advised to use caution when driving or operating machines as BLENREP may 

affect their vision.  

 
4.8 Undesirable effects  

 

Summary of the safety profile 

 

Adverse reactions described in this section were reported from 95 patients who received BLENREP 

2.5 mg/kg in study 205678. The most frequent adverse reactions (≥30%) were keratopathy (71%) and 

thrombocytopenia (38%). The most commonly reported serious adverse reactions were pneumonia 

(7%), pyrexia (7%) and IRRs (3%). Permanent discontinuation due to an adverse reaction occurred in 

9% of patients who received BLENREP with 3% related to ocular adverse reactions. 

 

Tabulated list of adverse reactions 

 

Table 3 summarises adverse drug reactions that occurred in patients receiving the recommended dose 

of BLENREP 2.5 mg/kg once every 3 weeks.  

 

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) and very rare (< 1/10,000). Within each frequency 

grouping, where relevant, adverse reactions are presented in order of decreasing seriousness. 

 

Table 3. Adverse reactions reported in multiple myeloma patients treated with BLENREP 

System Organ Class Adverse reactionsa  Frequency Incidence (%) 

Any 

Grade  

Grade 

3-4  

Infections and 

infestations 

Pneumoniab Very common 11 7 

Upper respiratory tract infection Common 9 0 

Blood and lymphatic 

system disorders  

Thrombocytopeniac Very common  38 22 

Anaemia 27 21 

Lymphopeniad 20 17 

Leukopeniae 17 6 

Neutropeniaf 15 11 

Eye disorders Keratopathyg Very common 71 31 

Blurred vision eventsh 25 4 

Dry eye eventsi 15 1 

Photophobia Common 4 0 

Eye irritation  3 0 

 Ulcerative keratitis  Uncommon 1 1 

 Infective keratitis   1 1 

Gastrointestinal 

disorders 
Nausea Very common 25 0 

Diarrhoea  13 1 



 

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 Vomiting Common 7 2 

General disorders and 

administration site 

conditions 

Pyrexia Very common 23 4 

Fatigue  16 2 

Investigations Increased aspartate aminotransferase  Very common 21 2 

Increased gamma glutamyltransferase 11 3 

 Increased creatine phosphokinase Common 5 2 

Injury, poisoning and 

procedural complications  

Infusion-related reactionsj Very common 21 3 

a Adverse reactions coded using MedDRA and graded for severity based CTCAE v4.03. 
b Includes pneumonia and herpes simplex pneumonia 
c Includes thrombocytopenia and decreased platelet count. 
d Includes lymphopenia and decreased lymphocyte count. 
e Includes leukopenia and decreased leukocyte count. 
f  Includes neutropenia and decreased neutrophil count. 
g Based on eye examination, characterised as corneal epithelium changes with or without symptoms. 

h Includes diplopia, vision blurred, visual acuity reduced, and visual impairment.  
i Includes dry eye, ocular discomfort, and eye pruritus.  
j Includes events determined by investigators to be related to infusion. Infusion reactions may include, 

but are not limited to, pyrexia, chills, diarrhea, nausea, asthenia, hypertension, lethargy, tachycardia. 

 

Description of selected adverse reactions 

 

Corneal adverse reactions 

 

Corneal adverse reactions were assessed in Study 205678 from the safety population (n = 218) which 

included patients treated with 2.5 mg/kg (n=95). Eye disorder events occurred in 74% patients and the 

most common adverse reactions were keratopathy or microcyst-like epithelial changes in corneal 

epithelium [identified on eye exam, with or without symptoms] (71%), blurred vision (25%), and dry 

eye symptoms (15%). Decreased vision (Snellen Visual Acuity worse than 20/50) in the better eye was 

reported in 18% and severe vision loss (20/200 or worse) in the better seeing eye was reported in 1% 

of patients treated with belantamab mafodotin. 

The median time to onset of Grade 2 or above corneal findings (best corrected visual acuity or 

keratopathy on eye examination) was 36 days (range: 19 to 143 days). The median time to resolution 

of these corneal findings was 91 days (range: 21 to 201 days).  

Corneal findings (keratopathy) led to dose delays in 47% of patients, and dose reductions in 27% of 

patients. Three percent of patients discontinued treatment due to ocular events. 

 

Infusion-related reactions 

 

In clinical studies, the incidence of infusion-related reactions (IRR) with belantamab mafodotin 

2.5 mg/kg was 21%, and most (90%) occurred during the first infusion. Most IRRs were reported as 

Grade 1 (6%) and Grade 2 (12%) while 3% experienced Grade 3 IRRs. Serious IRRs were reported by 

4% of patients and included symptoms of pyrexia and lethargy. Median time to onset and the median 

duration of the first occurrence of an IRR was 1 day. One patient (1%) discontinued treatment due to 

IRRs, experiencing Grade 3 IRRs at first and second infusion. No Grade 4 or 5 IRRs were reported.  

 

Thrombocytopenia 

 

Thrombocytopenic events, (thrombocytopenia and platelet count decreased) occurred in 38% of 

patients treated with belantamab mafodotin 2.5 mg/kg. Grade 2 thrombocytopenic events occurred in 

3% of patients, Grade 3 in 9%, and Grade 4 in 13%. Grade 3 bleeding events occurred in 2% of 

patients and no Grade 4 or 5 events were reported.  

 



 

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Infections 

 

Upper respiratory tract infections were commonly reported across the belantamab mafodotin clinical 

programme and were mostly mild to moderate (Grade 1 to 3), occurring in 9% of patients treated with 

belantamab mafodotin 2.5 mg/kg. There were no SAEs of upper respiratory tract infections reported.  

Pneumonia was the most frequent infection reported in 11% of patients treated with belantamab 

mafodotin 2.5 mg/kg. Pneumonia was also the most frequent SAE, reported in 7% of patients. 

Infections with a fatal outcome were primarily due to pneumonia (1%). 

 

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 national reporting system 

listed in Appendix V. 

 

4.9 Overdose 

 

There has been no experience of overdosage in clinical studies.  

 

There is no known specific antidote for belantamab mafodotin overdose. In the event of an overdose, 

the patient should be monitored for any signs or symptoms of adverse effects and appropriate 

supportive treatment should be instituted immediately. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1  Pharmacodynamic properties 

 

Pharmacotherapeutic group: antineoplastic agents, monoclonal antibodies, ATC code: L01XC39 

 

Mechanism of action 

 

Belantamab mafodotin is a humanised IgG1κ monoclonal antibody conjugated with a cytotoxic agent, 

maleimidocaproyl monomethyl auristatin F (mcMMAF). Belantamab mafodotin binds to cell surface 

BCMA and is rapidly internalised. Once inside the tumour cell, the cytotoxic agent is released 

disrupting the microtubule network, leading to cell cycle arrest and apoptosis. The antibody enhances 

recruitment and activation of immune effector cells, killing tumour cells by antibody-dependent 

cellular cytotoxicity and phagocytosis. Apoptosis induced by belantamab mafodotin is accompanied 

by markers of immunogenic cell death, which may contribute to an adaptive immune response to 

tumour cells. 

 

Pharmacodynamic effects 

 

Cardiac Electrophysiology 

Based on exposure-QTc analysis, belantamab mafodotin had no meaningful QTc prolongation (>10 

ms) at the recommended dose of 2.5 mg/kg once every 3 weeks. 

 

Immunogenicity 

 

In clinical studies in patients with multiple myeloma, <1% of patients (2/274) tested positive for anti-

belantamab mafodotin antibodies after receiving belantamab mafodotin. One of the two patients tested 

positive for neutralising anti-belantamab mafodotin antibodies. 

 

Clinical efficacy 

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 

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Study 205678 was an open-label, two arm, Phase II, multicentre study which evaluated belantamab 

mafodotin as monotherapy in patients with multiple myeloma who had relapsed following treatment 

with at least 3 prior therapies, and who were refractory to an immunomodulatory agent, a proteasome 

inhibitor and an anti-CD38 antibody alone or in combination. Patients were included if they had 

undergone autologous stem cell transplant or were considered transplant ineligible and had measurable 

disease by International Myeloma Working Group (IMWG) criteria. 

 

Patients were randomised to receive 2.5 mg/kg (N=97) or 3.4 mg/kg (N=99) belantamab mafodotin by 

intravenous infusion every 3 weeks until disease progression or unacceptable toxicity (see Table 4). 

The data presented below is from the 2.5 mg/kg cohort who received the recommended therapeutic 

dose based on overall benefit risk assessment (see section 4. 2).  

 

Table 4: Baseline demographics and disease characteristics 

Baseline Characteristics 2.5 mg/kg 

(N=97) 

Age  Median (range) 

Interquartile range 

65.0 (39-85) 

60-70 

Gender  Male 

Female 

51 (53%) 

46 (47%) 

ECOG at baseline 0/1 

2 

33%, 50%, 

17% 

ISS stage at screening II 

III  

33 (34%) 

42 (43%) 

Cytogenetics risk High risk* 26 (27%) 

Number of prior lines  Median 

Range 

7 

(3-21) 

Duration of exposure Median 

Range 

9 weeks  

(2-75) 

Treatment cycles Median 

Range 

3  

(1-17) 

*High risk cytogenetic factors [positive for t (4;14), t (14;16), and 117p13del] 

 

The primary endpoint was overall response rate as evaluated by an Independent Review Committee 

(IRC) based on the IMWG Uniform Response Criteria for Multiple Myeloma. Table 5 provides the 

results of study 205678.  

 

Table 5. Efficacy of BLENREP in patients with multiple myeloma in study 205678 

Clinical response 
2.5 mg/kg  

(N = 97) 

Overall response rate (ORR), % (97.5% CI) 32% (22, 44) 

Stringent complete response (sCR), n (%) 2 (2%) 

Complete response (CR), n (%) 5 (5%) 

Very good partial response (VGPR), n (%) 11 (11%) 

Partial response (PR), n (%) 13 (13%) 

Clinical benefit rate*, n (%) (95% CI) 36 (26.6, 46.5) 

Median duration of response in months (95% CI) 11 (4.2 to Not reached) 

Probability of Maintaining Response at 12 Months (95% CI) 0.50 (0.29, 0.68) 

Median time to response in months (95% CI) 1.5 (1.0, 2.1) 

Median time to best response in months (95% CI) 2.2 (1.5, 3.6) 

Median overall survival (OS) in months (95% CI)  13.7 (9.9 to Not reached) 

Survival probability at 12 Months (95% CI) 0.57 (0.46, 0.66) 

*CBR: sCR+CR+VGPR+PR+Minimal response 

 

Paediatric population 



 

11 

 

The European Medicines Agency has waived the obligation to submit the results of studies with 

BLENREP in all subsets of the paediatric population in multiple myeloma (see section 4.2 for 

information on paediatric use). 

 

This medicinal product has been authorised under a so-called ‘conditional approval’ scheme. This 

means that further evidence on this medicinal product is awaited. 

 

The European Medicines Agency will review new information on this medicinal product at least every  

year and this SmPC will be updated as necessary. 

 

5.2 Pharmacokinetic properties  

 

Absorption 

 

Maximum concentration for belantamab mafodotin occurred at or shortly after the end of infusion 

while cys-mcMMAF concentrations peaked ~24 hours after dosing. Geometric mean belantamab 

mafodotin Cmax and AUC(0-tau) concentrations were 43 mcg/mL and 4,666 mcg.h/mL, respectively. 

Geometric mean cys-mcMMAF Cmax and AUC(0-168h) concentrations were 0.90 ng/mL and 84 ng.h/mL, 

respectively. 

 

Distribution 

 

The mean steady-state volume of distribution of belantamab mafodotin was 10.8 L. 

 

Biotransformation 

 

The monoclonal antibody portion of belantamab mafodotin is expected to undergo proteolysis to small 

peptides and individual amino acids by ubiquitous proteolytic enzymes. Cys-mcMMAF had limited 

metabolic clearance in human hepatic S9 fraction incubation studies. 

 

Drug interactions 

 

In vitro studies demonstrated that cys-mcMMAF is a substrate of organic anion transporting 

polypeptide (OATP)1B1 and OATP1B3, multidrug resistance-associated protein (MRP)1, MRP2, 

MRP3, bile salt export pump (BSEP), and a possible substrate of P-glycoprotein (P-gp). 

 

Elimination 

 

Belantamab mafodotin was cleared slowly with total plasma clearance of 0.92 L/day and a terminal 

phase half-life of 12 days. Over time, clearance was reduced to 0.72 L/day with an elimination half-

life of 14 days. Predose cys-mcMMAF concentrations at each dose were typically below the limit of 

quantification (0.05 ng/mL). 

 

In an animal study, approximately 83% of the radioactive dose was excreted in the faeces; urinary 

excretion (approximately 13%) was a minor route; intact cys-mcMMAF was detected in human urine, 

with no evidence of other MMAF-related metabolites. 

 

Linearity/non-linearity 

 

Belantamab mafodotin exhibits dose-proportional pharmacokinetics over the recommended dose range 

with a reduction in clearance over time. 

 

Special populations 

 

Elderly patients (≥65 years old) 



 

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No formal studies have been conducted in elderly patients. Age was not a significant covariate in 

population pharmacokinetic analyses. 

 

Renal impairment 

No formal studies have been conducted in patients with renal impairment.  Renal function was not a 

significant covariate in population pharmacokinetic analyses that included patients with normal renal 

function and mild or moderate renal impairment. 

 

Hepatic impairment 

No formal studies have been conducted in patients with hepatic impairment.  Hepatic function was not 

a significant covariate in population pharmacokinetic analyses that included patients with normal 

hepatic function or mild hepatic impairment. 

 

Body weight 

Body weight was a significant covariate in population pharmacokinetic analyses. Belantamab 

mafodotin Ctau was predicted to be +10% at a body weight of 100 kg (+20% for 130 kg) and -10% at a 

body weight of 55 kg (-20% for 40 kg) compared to the typical patient (75 kg). 

 

5.3 Preclinical safety data 

 

Animal toxicology and/or pharmacology 

 

In non-clinical studies, the principal adverse findings (directly related to belantamab mafodotin) in the 

rat and monkey, at exposures ≥1.2 times of the recommended clinical dose of 2.5 mg/kg, were 

elevated liver enzymes sometimes associated with hepatocellular necrosis at ≥ 10 and ≥3 mg/kg, 

respectively, and increases in alveolar macrophages associated with eosinophilic material in the lungs 

at ≥3 mg/kg (rat only).Most findings in animals were related to the cytotoxic drug conjugate, the 

histopathological changes observed in the testes and lungs, were not reversible in rats. 

 

Single cell necrosis in the corneal epithelium and/or increased mitoses of corneal epithelial cells was 

observed in rat and rabbit. Belantamab mafodotin was taken up into cells throughout the body by a 

mechanism unrelated to BCMA receptor expression on the cell membrane.  

 

Carcinogenesis/mutagenesis 

 

Belantamab mafodotin was genotoxic in an in vitro screening assay in human lymphocytes, consistent 

with the pharmacological effect of cys-mcMMAF-mediated disruption of microtubules causing 

aneuploidy. 

No carcinogenicity or definitive genotoxicity studies have been conducted with belantamab mafodotin. 

 

Reproductive Toxicology 

 

No animal studies have been performed to evaluate the potential effects of belantamab mafodotin on 

reproduction or development. The mechanism of action is to kill rapidly dividing cells which would 

affect a developing embryo which has rapidly dividing cells. There is also a potential risk of heritable 

changes via aneuploidy in female germ cells. 

 

Effects on male and female reproductive organs have been observed in animals at doses of 

≥ 10 mg/kg, which is approximately 4 times the exposure of the clinical dose. Luteinized nonovulatory 

follicles were seen in the ovaries of rats after 3 weekly doses. Findings in male reproductive organs, 

that were adverse and progressed following repeat dosing in rat, included marked 

degeneration/atrophy of seminiferous tubules that generally did not reverse following dosing 

cessation.  

 

 

6. PHARMACEUTICAL PARTICULARS 

 



 

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6.1 List of excipients 

 

Sodium citrate  

Citric acid 

Trehalose dihydrate  

Disodium edetate  

Polysorbate 80  

 

6.2 Incompatibilities 

 

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 

products. 

 

6.3 Shelf life 

 

Unopened vial 

 

24 months. 

 

Reconstituted solution 

 

The reconstituted solution can be stored for up to 4 hours at room temperature (20ºC to 25ºC) or stored 

in a refrigerator (2°C to 8°C) for up to 4 hours. Do not freeze. 

 

Diluted solution 

 

From a microbiological point of view, the product should be used immediately. If not used 

immediately, the diluted solution can be stored in a refrigerator (2ºC to 8ºC) prior to administration for 

up to 24 hours. Do not freeze. If refrigerated, allow the diluted solution to equilibrate to room 

temperature prior to administration. 

 

The diluted infusion solution may be kept at room temperature (20ºC to 25ºC) for a maximum of 6 

hours (including infusion time). 

 

6.4 Special precautions for storage 

 

Store in a refrigerator (2ºC to 8ºC). 

 

For storage conditions after reconstitution of the medicinal product, see section 6.3. 

 

6.5 Nature and contents of container  

 

Type 1 glass vial sealed with bromobutyl rubber stopper and aluminium overseal with a plastic 

removable cap containing 100 mg powder. 

 

Pack size: 1 vial 

 

6.6 Special precautions for disposal and other handling 

 

Preparation of solution for infusion 

 

BLENREP is a cytotoxic anticancer medicinal product. Proper handling procedures should be 

followed. Use aseptic technique for the reconstitution and dilution of the dosing solution.  

 

The recommended dose of BLENREP is 2.5 mg/kg administered as an intravenous infusion once 

every 3 weeks. 

 



 

14 

Calculate the dose (mg), total volume (mL) of solution required and the number of vials needed based 

on the patient’s actual body weight (kg). 

Reconstitution  

1. Remove the vial(s) of BLENREP from the refrigerator and allow to stand for approximately 10 

minutes to reach room temperature.  

2. Reconstitute each vial with 2 mL of water for injections to obtain a concentration of 50 mg/mL. 

Gently swirl the vial to aid dissolution. Do not shake. 

3. Visually inspect the reconstituted solution for particulate matter and discoloration. The 

reconstituted solution should be a clear to opalescent, colourless to yellow to brown liquid. 

Discard the reconstituted vial if extraneous particulate matter other than translucent to white 

proteinaceous particles is observed. 

 

Dilution Instructions for Intravenous Use 

1. Withdraw the necessary volume for the calculated dose from each vial. 

2. Add the necessary amount of BLENREP to the infusion bag containing 250 mL of sodium chloride 

9 mg/mL (0.9%) solution for injection. Mix the diluted solution by gentle inversion. The final 

concentration of the diluted solution should be between 0.2 mg/mL to 2 mg/mL. DO NOT 

SHAKE. 

3. Discard any unused reconstituted solution of BLENREP left in the vial. 
 

If the diluted solution is not used immediately, it may be stored in a refrigerator (2ºC to 8ºC) for up to 

24 hours prior to administration. If refrigerated, allow the diluted solution to equilibrate to room 

temperature prior to administration. The diluted solution may be kept at room temperature (20ºC to 

25ºC) for a maximum of 6 hours (including infusion time). 

Administration Instructions 

1. Administer the diluted solution by intravenous infusion over a minimum of 30 minutes using an 

infusion set made of polyvinyl chloride or polyolefin. 

2. Filtration of the diluted solution is not required. However, if the diluted solution is filtered, 

polyethersulfone (PES) based filter is recommended. 

 

Disposal 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

GlaxoSmithKline (Ireland) Limited 

12 Riverwalk, Citywest Business Campus 

Dublin 24 

Ireland 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/20/1474/001 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 25 August 2020 



 

15 

 

10. DATE OF REVISION OF THE TEXT 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu. 

 

  

http://www.ema.europa.eu/


 

16 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE 

SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR 

BATCH RELEASE 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 

PRODUCT 

 

E. SPECIFIC OBLIGATION TO COMPLETE POST-

AUTHORISATION MEASURES FOR THE CONDITIONAL 

MARKETING AUTHORISATION 

 



 

17 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 

MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturer of the biological active substance 

 

Sigma-Aldrich Manufacturing LLC 

3300 South Second Street, 

St. Louis, MO 63118 

USA 

 

Name and address of the manufacturer responsible for batch release 

 

GlaxoSmithKline Manufacturing SpA 

Strada Provinciale Asolana, 90, 

San Polo di Torrile, Parma 43056, 

Italy 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE  

 

Medicinal product subject to restricted medical prescription. (See Annex I: Summary of Product 

Characteristics, section 4.2) 

 

 

C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

• Periodic safety update reports (PSURs) 

 

The requirements for submission of PSURs for this medicinal product are set out in the list of 

Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC 

and any subsequent updates published on the European medicines web-portal. 

The marketing authorisation holder (MAH) shall submit the first PSUR periodic safety update 

report for this product within 6 months following authorisation. 

 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT   

 

• Risk management plan (RMP) 

 

The marketing authorisation holder (MAH) shall perform the required pharmacovigilance 

activities and interventions detailed in the agreed RMP presented in Module 1.8.2 of the 

marketing authorisation and any agreed subsequent updates of the RMP. 

 

An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 

• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 

an important (pharmacovigilance or risk minimisation) milestone being reached. 

 

• Additional risk minimisation measures 

 

The educational programme is aimed at helping haematologists/oncologists, eye care professionals and 

patients understand the corneal risks associated with belantamab mafodotin, so that corneal 

examination findings, and/or visual changes can be promptly identified and managed according to the 

product labelling. 



 

18 

 

Prior to the launch of BLENREP (belantamab mafodotin) in each Member State the MAH must agree 

about the content and format of the educational materials, including communication media, 

distribution modalities, and any other aspects of the programme with the National Competent 

Authority.  

 

The MAH shall ensure that in each Member State where BLENREP (belantamab mafodotin) is 

marketed, all healthcare professionals and patients/carers who are expected to prescribe, dispense and 

receive BLENREP (belantamab mafodotin) have access to/are provided with the following 

educational materials to be disseminated through professional bodies consisting of the following: 

• Educational materials for Healthcare professionals (HCPs) (includes 

haematologists/oncologists/eye care professionals):  

o Corneal adverse reaction guides 

o Eye care screening sheet 

 

• Educational materials for the patient 

o Corneal adverse reaction guides 

o Patient and pharmacy eye drop wallet cards. 

 

• Summary of the Product Characteristics (SmPC) and Package Leaflet (PL)  

 

Key elements to be included 

 

The healthcare professional’s corneal adverse reaction guides 

 

The HCPs corneal adverse reaction guides will contain the following key information: 

 
Relevant information of the safety concern keratopathy or microcyst-like epithelial changes in the 

corneal epithelium: 

 

• Advise patients that corneal adverse reactions may occur during treatment.  

• Patients with a history of dry eyes are more prone to develop changes in the corneal 

epithelium. 

 

Details on how to minimise the safety concern addressed by the additional risk minimisation measures 

through appropriate monitoring: 

• Ophthalmic examinations, including assessment of visual acuity and slit lamp examination, 

should be performed at baseline, before the subsequent 3 treatment cycles, and as clinically 

indicated whilst on treatment. 

• Patients experiencing keratopathy with or without changes in visual acuity may require a dose 

modification (delay and/or reduction) or treatment discontinuation based on severity of 

findings. 

• Emphasise the need to consult the SmPC.  

 

Key messages to convey during patient counselling:  

 

• Patients should be advised to administer preservative-free artificial tears at least 4 times a day 

during treatment.   

• Patients should avoid using contact lenses until the end of treatment.  

• Patients should consult their haematologist/oncologist if corneal adverse reactions occur.  

• Patients who report corneal symptoms should be referred to an eye care professional.  

• Patients should be advised to use caution when driving or operating machinery.  

 

Healthcare professionals’ training material 

 



 

19 

Anatomy and physiology of the eye:  

• Images of the eye are provided and reviewed. 

• Keratopathy is characterised based on exam findings and patient reported outcomes. 

 

Description of eye exams: 

• Use of slit lamp exams provide detailed information on the anatomical structures in the eye. 

They can help detect a range of conditions, including keratopathy or microcyst-like epithelial 

changes in the corneal epithelium (as seen on eye examination).  

• Description of visual acuity provides a measure of the visual system’s ability to discern fine 

distinctions in the visual environment.  

• Best corrected visual acuity (BCVA) refers to the visual acuity achieved with correction (such 

as glasses), as measured on the standard Snellen Visual Acuity Chart, monocularly and 

binocularly.  

• Summary of visual acuity scores (20/20 vs <20/20) and how a score less than 20/20 can be 

corrected and managed by the patients.  

 

Eye care screening sheet: 

• Includes important information related to corneal adverse reactions associated with 

belantamab mafodotin, adverse event management, and instructions to facilitate 

communication between prescribers and eye care professionals for patients.  

 

Patient corneal adverse reaction guides 

 

The patient corneal adverse reaction guides will contain the following key information:  

• Corneal adverse reactions may occur during treatment. Patients with a history of dry eyes are 

more prone to develop changes in the corneal epithelium.  

• Ophthalmic examinations, including assessment of visual acuity and slit lamp examination, 

should be performed at baseline, before the subsequent 3 treatment cycles, and as clinically 

indicated whilst on treatment.  

• Patients experiencing keratopathy with or without changes in visual acuity may require a dose 

modification (delay and/or reduction) or treatment discontinuation based on severity of 

findings.   

• Tell your haematologist/oncologist about any history of vision or eye problems.  

• Consult the PL.  

 

A description of the sign and symptoms of the risk of keratopathy:  

 

• If you experience changes with your vision whilst on belantamab mafodotin, contact your 

haematologist/oncologist. Symptoms include the following:  

o redness, dryness, itching, burning sensation, or sandy or gritty sensation in their eyes;  

o sensitivity to light;  

o blurred vision;  

o pain in their eyes;  

o excessive watering of their eyes.  

 

• If you experience changes in your vision or eyes after initiating treatment (changes have 

improved, persisted, or worsened since your last appointment), contact your 

haematologist/oncologist.  

 

• Your HCP will ask you to use eye drops called preservative-free artificial tears during 

treatment. Administer them as instructed.  

 

 

Patient eye drop wallet card:  



 

20 

• Patient wallet card indicates the patient is on treatment with belantamab mafodotin and 

contains contact information for the haematologist/oncologist and the eye care professional.  

• Present to HCPs during follow up visits. 

 

Pharmacy eye drop wallet card:  

• Patients to present the pharmacy wallet card to the pharmacist to find eye drops called 

preservative-free artificial tears for use, as directed. 

 

 

E. SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURES 

 FOR THE CONDITIONAL MARKETING AUTHORISATION 

 

This being a conditional marketing authorisation and pursuant to Article 14-a(4) of Regulation (EC) 

No 726/2004, the MAH shall complete, within the stated timeframe, the following measures: 

 

Description Due date 

In order to confirm the efficacy and safety of BLENREP in relapsed/refractory 

multiple myeloma adult patients, who have received at least four prior therapies 

and whose disease is refractory to at least one proteasome inhibitor, one 

immunomodulatory agent, and an anti-CD38 monoclonal antibody, and who have 

demonstrated disease progression on the last therapy, the MAH should submit the 

results of the DREAMM-2 (205678) study investigating the efficacy of 

belantamab mafodotin in patients with multiple myeloma who had 3 or more 

prior lines of treatment, are refractory to a proteasome inhibitor and an 

immunomodulatory agent and have failed an anti-CD38 antibody. 

April 2021 

In order to confirm the efficacy and safety of BLENREP in multiple myeloma 

adult patients, who have received at least four prior therapies and whose disease 

is refractory to at least one proteasome inhibitor, one immunomodulatory agent, 

and an anti-CD38 monoclonal antibody, and who have demonstrated disease 

progression on the last therapy, the MAH should submit the results of the 

DREAMM-3 (207495) study comparing the efficacy of belantamab mafodotin 

vs. pomalidomide plus low dose dexamethasone (pom/dex) in patients with 

relapsed/refractory multiple myeloma. 

July 2024 

 

 

  



 

21 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

  



 

22 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 

  



 

23 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

BLENREP 100 mg powder for concentrate for solution for infusion 

belantamab mafodotin 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each vial contains 100 mg of belantamab mafodotin (50 mg/ mL after reconstitution) 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains: sodium citrate, citric acid, trehalose dihydrate, disodium edetate, polysorbate 80. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder for concentrate for solution for infusion. 

 

1 vial. 

 

 

5. METHOD AND ROUTEOF ADMINISTRATION 

 

For intravenous infusion after reconstitution and dilution. 

Read the package leaflet before use.  

For single use only. 

 

Press here to open 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

Cytotoxic: handle with caution 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 



 

24 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

GlaxoSmithKline (Ireland) Limited, 12 Riverwalk, Citywest Business Campus, Dublin 24, Ireland. 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/20/1474/001 

  

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Justification for not including Braille accepted. 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC  

SN  

NN 

  



 

25 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

BLENREP 100 mg powder for concentrate  

belantamab mafodotin 

IV 

cytotoxic 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

100 mg 

 

 

6. OTHER 

 

 

  



 

26 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 



 

27 

Package leaflet: Information for the patient 

 

BLENREP 100 mg powder for concentrate for solution for infusion  

belantamab mafodotin 

 

This medicine is subject to additional monitoring. This will allow quick identification of new 

safety information. You can help by reporting any side effects you may get. See the end of section 4 

for how to report side effects. 

 

Read all of this leaflet carefully before you are given this medicine because it contains important 

information for you. 

- Keep this leaflet. You may need to read it again.  

- If you have any further questions, ask your doctor or nurse. 

- If you get any side effects, talk to your doctor or nurse. This includes any possible side effects 

not listed in this leaflet. See section 4. 

 

What is in this leaflet 

 

1. What BLENREP is and what it is used for  

2. What you need to know before you are given BLENREP 

3. How BLENREP is given  

4. Possible side effects  

5. How to store BLENREP 

6. Contents of the pack and other information 

 

1. What BLENREP is and what it is used for 

 

BLENREP contains the active substance belantamab mafodotin, a monoclonal antibody connected to 

an anticancer substance that can kill multiple myeloma cells. The monoclonal antibody is a protein 

designed to find the multiple myeloma cancer cells in your body and bind to them.  

Once attached to the cancer cells, the anticancer substance is released and kills the cancer cells. 

 

BLENREP is used to treat adults who have cancer of the bone marrow called multiple myeloma. 

 

2. What you need to know before you are given BLENREP  

 

Do not receive BLENREP: 

- if you are allergic to belantamab mafodotin or any of the other ingredients of this medicine 

(listed in section 6).  

➔ Check with your doctor if you think this applies to you. 

Warnings and precautions  

Eye problems 

BLENREP can cause dry eyes, blurred vision or other eye problems. 

You should have an eye examination by an eye specialist before starting treatment and for the next 

three doses of BLENREP. Your doctor may request further eye tests whilst on treatment with 

BLENREP. Even if your vision seems fine, it is important that you get your eyes checked during 

treatment with BLENREP because some changes can happen without symptoms and may only be seen 

on an eye examination. 

➔ Do not use contact lenses while you are receiving treatment. 

Your doctor will ask you to use eye drops called preservative-free artificial tears at least 4 times a day 

during treatment to moisten and lubricate your eyes. You should apply them as instructed. 



 

28 

If you notice changes with your vision, your doctor may hold treatment with BLENREP or adjust the 

dose or ask you to see an eye specialist. Your doctor may decide to stop treatment with BLENREP. 

➔ Contact your doctor if you have blurred vision or other eye problems.  

Abnormal bruising and bleeding  

 

BLENREP can decrease the number of blood cells called platelets which help to clot your blood.  

Symptoms of low platelets counts (thrombocytopenia) include: 

• abnormal bruising under the skin, 

• bleeding longer than usual after a test, 

• bleeding from your nose or your gums or more serious bleeding.  

 

Your doctor will ask you to have a blood test before you start treatment, and regularly during 

treatment with BLENREP, to check that your platelet levels are normal. 

➔ Tell your doctor if you develop abnormal bleeding or bruising, or any symptoms that worry 

you. 

Infusion-related reactions 

 

BLENREP is given by a drip (infusion) into a vein. Some people who receive infusions develop 

infusion-related reactions. 

➔ See ‘Infusion-related reactions’ in Section 4.  

If you have previously had a reaction to an infusion of BLENREP, or any other medicine: 

➔ Tell your doctor or nurse before you receive another infusion. 

 

Children and adolescents 

 

This medicine is not intended for use in children or adolescents below 18 years of age. 

 

Other medicines and BLENREP 

➔ Tell your doctor if you are taking, have recently taken or might take any other medicines. 

 

Pregnancy and fertility 

 

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby: 

➔ Tell your doctor before you are given this medicine. 

 

If you are a woman who could become pregnant: 

• Your doctor will ask you to take a pregnancy test before you start treatment with BLENREP. 

• You must use effective contraception during treatment and for 4 months after your last dose 

of BLENREP.  

Women being treated with this medicine who wish to have children are advised to seek fertility 

counselling and consider options to freeze eggs/embryos before treatment. 

 

If you are a man who could father a child: 

• You must use effective contraception during treatment and for 6 months after your last dose 

of BLENREP. 

Men being treated with this medicine are advised to have sperm samples frozen and stored before 

treatment. 

 

Breast-feeding 

 

You must not breast-feed during treatment and for 3 months after your last dose of BLENREP. 



 

29 

It is not known if the medicine passes into breast milk. Talk to your doctor about this. 

Driving and using machines 

 

BLENREP can cause problems with vision that can affect your ability to drive or use machines. 

➔ Do not drive or use machines unless you are sure your vision is not affected. Talk to your 

doctor if you are not sure. 

BLENREP contains sodium  

This medicine contains less than 1 mmol sodium (23 mg) per 100 mg dose, that is to say essentially 

“sodium-free”. 

3. How BLENREP is given 

 

Your doctor will decide on the correct dose of BLENREP. The dose is calculated based on your body 

weight. 

 

The recommended dose is 2.5 mg of BLENREP per kilogram of your body weight. It is given by your 

doctor or nurse as a drip into a vein (intravenous infusion) every three weeks. 

 

Before your infusion, you should apply lubricating and moistening eye drops (preservative-free 

artificial tears). You should continue to use the eye drops at least 4 times a day whilst  you are 

receiving treatment with BLENREP. 

If you given more BLENREP than you should 

 

This medicine will be given by your doctor or nurse. In the unlikely event that you are given too much 

(an overdose) your doctor will check you for side effects. 

If a dose of BLENREP is missed 

 

It is very important to go to all your appointments, to make sure your treatment works. If you miss an 

appointment, make another one as soon as possible. 

➔ Contact your doctor or hospital as soon as possible to re-schedule your appointment. 

 

4. Possible side effects 

 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

Infusion-related reactions 

Some people may have allergic-like reactions when they receive an infusion. These usually develop 

within minutes or hours but may develop up to 24 hours after treatment. 

Symptoms include: 

• flushing 

• chills 

• fever 

• difficulty breathing 

• rapid heartbeat 

• drop in blood pressure. 

➔ Get medical help immediately if you think you may be having a reaction. 

 

Other side effects 

 



 

30 

Tell your doctor or nurse if you notice any of the following side effects: 

Very common: may affect more than 1 in 10 people 

• eye problems, including disorder of the cornea of the eye (keratopathy), blurred vision, and 

dry eyes. 

➔ Read the information under ‘Eye problems’ in Section 2 of this leaflet. 

• low number of a type of blood cell called platelets which help to clot blood 

(thrombocytopenia), causing abnormal bruising and bleeding 

➔ Read the information under ‘Abnormal bruising and bleeding’ in Section 2 of this leaflet. 

• infection of the lungs (pneumonia) 

• fever 

• low number of red blood cells which carry oxygen in the blood (anaemia), causing weakness 

and fatigue. 

• low number of white blood cells in the blood (lymphopenia, leukopenia, neutropenia). 

• abnormal blood levels of enzymes indicating liver problems (aspartate aminotransferase, 

gamma glutamyltransferase). 

• nausea 

• feeling tired (fatigue) 

• diarrhoea  

Common:  may affect up to 1 in 10 people 

• cold or cold-like symptoms such as cough, runny nose or sore throat. 

• vomiting 

• abnormal levels of creatinine phosphokinase 

• sensitivity to light (photophobia) 

• eye irritation 

Uncommon: may affect up to 1 in 100 people 

• eye sores, possibly with infection (ulcerative and infective keratitis) 

Reporting of side effects 

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not 

listed in this leaflet. You can also report side effects directly via the national reporting system listed in 

Appendix V. By reporting side effects you can help provide more information on the safety of this 

medicine. 

 

 

5. How to store BLENREP 

 

Keep this medicine out of the sight and reach of children. 

Do not use this medicine after the expiry date which is stated on the label and carton after EXP. The 

expiry date refers to the last day of that month. 

Store in a refrigerator (2ºC–8ºC). 

 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 

throw away medicines you no longer use. These measures will help protect the environment. 

 

 

6. Contents of the pack and other information 

 

What BLENREP contains 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 

31 

 

The active substance is belantamab mafodotin. One vial of powder contains 100 mg of belantamab 

mafodotin. After reconstitution the solution contains 50 mg belantamab mafodotin per mL. 

 

The other ingredients are sodium citrate, citric acid, trehalose dihydrate, disodium edetate and 

polysorbate 80 (see section 2 “BLENREP contains sodium”). 

 

What BLENREP looks like and contents of the pack 

 

BLENREP is presented as a white to yellow powder in a glass vial with a rubber stopper and a plastic 

removable cap. Each carton contains one vial. 

 

 

Marketing Authorisation Holder 

GlaxoSmithKline (Ireland) Limited 

12 Riverwalk  

Citywest Business Campus 

Dublin 24 

Ireland 

 

Manufacturer 

GlaxoSmithKline Manufacturing SpA 

Strada Provinciale Asolana, 90 

San Polo di Torrile, Parma 43056 

Italy 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 

GlaxoSmithKline Pharmaceuticals s.a./n.v. 

Tél/Tel: + 32 (0) 10 85 52 00 

 

Lietuva 

GlaxoSmithKline Lietuva UAB 

Tel: + 370 5 264 90 00 

info.lt@gsk.com 

 

България 

ГлаксоСмитКлайн ЕООД  

Teл.: + 359 2 953 10 34 

 

Luxembourg/Luxemburg 

GlaxoSmithKline Pharmaceuticals s.a./n.v. 

Belgique/Belgien 

Tél/Tel: + 32 (0) 10 85 52 00 

 

Česká republika 

GlaxoSmithKline, s.r.o. 

Tel: + 420 222 001 111 

cz.info@gsk.com 

Magyarország 

GlaxoSmithKline Kft. 

Tel.: + 36 1 225 5300 

 

Danmark 

GlaxoSmithKline Pharma A/S 

Tlf: + 45 36 35 91 00 

dk-info@gsk.com 

 

Malta 

GlaxoSmithKline (Malta) Limited 

Tel: + 356 21 238131 

Deutschland 

GlaxoSmithKline GmbH & Co. KG 

Tel.: + 49 (0)89 36044 8701 

produkt.info@gsk.com 

 

Nederland 

GlaxoSmithKline BV 

Tel: + 31 (0) 33 2081100  

Eesti Norge 

https://doris.fimea.fi/dorisdav/nodes/22308188/cz.info%40gsk.com


 

32 

GlaxoSmithKline Eesti OÜ 

Tel: + 372 6676 900 

estonia@gsk.com  

GlaxoSmithKline AS 

Tlf: + 47 22 70 20 00 

 

 

Ελλάδα 

GlaxoSmithKline Μονοπρόσωπη A.E.B.E. 

Τηλ: + 30 210 68 82 100 

 

Österreich 

GlaxoSmithKline Pharma GmbH 

Tel: + 43 (0)1 97075 0 

at.info@gsk.com 

 

España 

GlaxoSmithKline, S.A. 

Tel: + 34 900 202 700  

es-ci@gsk.com 

 

Polska 

GSK Services Sp. z o.o. 

Tel.: + 48 (0)22 576 9000 

France 

Laboratoire GlaxoSmithKline 

Tél: + 33 (0)1 39 17 84 44 

diam@gsk.com 

 

Portugal 

GlaxoSmithKline – Produtos Farmacêuticos, Lda. 

Tel: + 351 21 412 95 00 

FI.PT@gsk.com  

Hrvatska 

GlaxoSmithKline d.o.o. 

Tel: +385 1 6051999 

 

România 

GlaxoSmithKline (GSK) S.R.L.  

Tel: + 4021 3028 208 

Ireland 

GlaxoSmithKline (Ireland) Limited 

Tel: + 353 (0)1 4955000 

 

Slovenija 

GlaxoSmithKline d.o.o. 

Tel: + 386 (0)1 280 25 00 

medical.x.si@gsk.com 

 

Ísland 

Vistor hf. 

Sími: + 354 535 7000 

 

Slovenská republika 

GlaxoSmithKline Slovakia s. r. o. 

Tel: + 421 (0)2 48 26 11 11 

recepcia.sk@gsk.com 

 

Italia 

GlaxoSmithKline S.p.A. 

Tel: + 39 (0)45 9218 111 

Suomi/Finland 

GlaxoSmithKline Oy 

Puh/Tel: + 358 (0)10 30 30 30 

Finland.tuoteinfo@gsk.com 

 

Κύπρος 

GlaxoSmithKline (Cyprus) Ltd 

Τηλ: + 357 22 39 70 00 

gskcyprus@gsk.com  

Sverige 

GlaxoSmithKline AB 

Tel: + 46 (0)8 638 93 00 

info.produkt@gsk.com 

 

Latvija 

GlaxoSmithKline Latvia SIA 

Tel: + 371 67312687 

lv-epasts@gsk.com 

 

United Kingdom 

GlaxoSmithKline UK Ltd 

Tel: + 44 (0)800 221441 

customercontactuk@gsk.com 

 

 

This leaflet was last revised in <{MM/YYYY}><{month YYYY}>. 

 

This medicine has been given ‘conditional approval’. This means that there is more evidence to come 

about this medicine. 

The European Medicines Agency will review new information on this medicine at least every year and 

this leaflet will be updated as necessary. 

 



 

33 

Other sources of information 

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu. 

 

------------------------------------------------------------------------------------------------------------------------ 

http://www.ema.europa.eu/


 

34 

The following information is intended for healthcare professionals only: 

 

Step-by-step instructions for use and handling, reconstitution, and administration 

 

The trade name and batch number of the administered product should be clearly recorded in the patient 

file. 

 

Preparation of solution for infusion 

 

BLENREP is a cytotoxic anticancer medicinal product. Proper handling procedures should be 

followed. Use aseptic technique for the reconstitution and dilution of the dosing solution. 

 

The recommended dose of BLENREP is 2.5 mg/kg administered as an intravenous infusion once 

every 3 weeks.  

 

Calculate the dose (mg), total volume (mL) of solution required and the number of vials needed based 

on the patient’s actual body weight (kg). 

 

Reconstitution 

1. Remove the vial(s) of BLENREP from the refrigerator and allow to stand for approximately 10 

minutes to reach room temperature. 

2. Reconstitute each vial with 2 mL of water for injections to obtain a concentration of 50 mg/mL. 

Gently swirl the vial to aid dissolution. Do not shake. 

3. Visually inspect the reconstituted solution for particulate matter and discoloration. The 

reconstituted solution should be a clear to opalescent, colourless to yellow to brown liquid. 

Discard the reconstituted vial if extraneous particulate matter other than translucent to white 

proteinaceous particles is observed. 

 

Dilution Instructions for Intravenous Use 

 

1. Withdraw the necessary volume for the calculated dose from each vial. 

2. Add the necessary amount of BLENREP to the infusion bag containing 250 mL of sodium chloride 

9 mg/mL (0.9%) solution for injection. Mix the diluted solution by gentle inversion. The final 

concentration of the diluted solution should be between 0.2 mg/mL to 2 mg/mL. DO NOT 

SHAKE. 

3. Discard any unused reconstituted solution of BLENREP left in the vial. 
 

If the diluted solution is not used immediately, it may be stored in a refrigerator (2ºC to 8ºC) for up to 

24 hours prior to administration. If refrigerated, allow the diluted solution to equilibrate to room 

temperature prior to administration. The diluted solution may be kept at room temperature (20ºC to 

25ºC) for a maximum of 6 hours (including infusion time). 

Administration Instructions 

1. Administer the diluted solution by intravenous infusion over a minimum of 30 minutes using an 

infusion set made of polyvinyl chloride or polyolefin. 

2. Filtration of the diluted solution is not required. However, if the diluted solution is filtered, 

polyethersulfone (PES) based filter is recommended. 

 

Disposal 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 



 

35 

 

 

 

 

 

 

 

 

 

 

Annex IV 

Conclusions on the granting of the conditional marketing authorisation and similarity 

presented by the European Medicines Agency 

 

 



 

36 

Conclusions presented by the European Medicines Agency on: 

• Conditional marketing authorisation 

The CHMP having considered the application is of the opinion that the risk-benefit balance is 

favourable to recommend the granting of the conditional marketing authorisation as further 

explained in the European Public Assessment Report. 

• Similarity  

The CHMP is of the opinion that Blenrep is not similar to authorised orphan medicinal products 

within the meaning of Article 3 of Commission Regulation (EC) No. 847/2000 as further explained 

in the European Public Assessment Report.  

 


	ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET
	Annex IV Conclusions on the granting of the conditional marketing authorisation and similarity presented by the European Medicines Agency