BLENREP

Treatment with Blenrep should be initiated and monitored by physicians experienced in the treatment of multiple myeloma. 4). Physicians should encourage patients to inform them of any ocular symptoms. 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). 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. 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. 5 mg/kg given once in Cycle 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.

9 mg/kg every 3 weeks Reduced dose level 2 NA NA = Not applicable. 1, Table 10). 4 mg/kg every 8 weeks NA = Not applicable. 1, Table 12). 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. 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 […]

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. 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. 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. 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 Incidence System organ class (SOC) Adverse Reactionsa Frequency All Grades (%) Grade 3+4 (%) Visual acuity reducedb 91 60Eye Disorders Corneal examination Very common 87 62 findingsb 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 […]

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. 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.

2). Patients should avoid using contact lenses until the end of treatment. Bandage contact lenses may be used under the direction of an ophthalmologist. 2). 8). These should be managed promptly and as clinically indicated by an eye care professional.

2). 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. 2). , 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. 8). 2). Pneumonitis Cases of pneumonitis, including fatal events, have been observed with Blenrep, although a causal association has not been established.

, cough, dyspnoea) must be performed to exclude possible pneumonitis. 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.

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