Posology : מינונים

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.

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)                   Continue treatment at current dose.
Mild superficial keratopathyb
Change in BCVA
Decline from baseline of 1 line on Snellen
Visual Acuity
Moderate    Corneal examination finding(s)                   Withhold treatment until Moderate superficial keratopathyc             improvement in examination findings and BCVA to mild
Change in BCVA severity or better.
Decline from baseline of 2 or 3 lines (and
Consider resuming treatment at a
Snellen Visual Acuity not worse than reduced dose of 1.9 mg/kg.
20/200)
Severe      Corneal examination finding(s)                   Withhold until improvement in Severe superficial keratopathyd               examination findings and BCVA to Corneal epithelial defecte                    mild severity or better.
For worsening symptoms that are
Change in BCVA unresponsive to appropriate
Decline from baseline of more than 3 lines on Snellen Visual Acuity                      management, consider discontinuation.


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                  Grade 2-3:         Consider withholding BLENREP and/or (see section 4.4)            Platelet count 25,000   reducing the dose of BLENREP to 1.9 mg/kg.
to less than
75,000/microlitres
Grade 4:          Withhold BLENREP until platelet count
Platelet count less    improves to Grade 3 or better. Consider than           resuming at a reduced dose of 1.9 mg/kg.
25,000/microlitres
Infusion-related reactions          Grade 2      Interrupt infusion and provide supportive (see section 4.4)                 (moderate)     treatment. Once symptoms resolve, resume at lower infusion rate by at least 50%.
Grade 3 or 4        Interrupt infusion and provide supportive
(severe)          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 under the age of 18 years 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. BLENREP should be infused over a minimum of 30 minutes (see section 6.6).