Empliciti

Elotuzumab therapy should be initiated and supervised by physicians experienced in the treatment of multiple myeloma. 4): ▪ Dexamethasone 8 mg intravenous ▪ H1 blocker: diphenhydramine (25-50 mg orally or intravenous) or equivalent H1 blocker.

▪ H2 blocker: ranitidine (50 mg intravenous or 150 mg orally) or equivalent H2 blocker. ▪ Paracetamol (650-1000 mg orally). Management of IRRs If a ≥ Grade 2 IRR occurs during Empliciti administration, the infusion must be interrupted.

5 mL/min every 30 minutes as tolerated to the rate at which the IRR occurred. If there is no recurrence of the IRR, the escalation can be resumed (see Tables 3 and 4). In patients who experience an IRR, vital signs should be monitored every 30 minutes for 2 hours after the end of the Empliciti infusion.

4). Very severe IRRs (≥ Grade 3) may require permanent discontinuation of Empliciti therapy and emergency treatment. Posology for administration with lenalidomide and dexamethasone The length of each treatment cycle is 28 days, see Table 1 for the dosing schedule.

Treatment should continue until disease progression or unacceptable toxicity. The recommended dose of Empliciti is 10 mg/kg body weight (bw) administered intravenously every week, on days 1, 8, 15, and 22 for the first two treatment cycles and every 2 weeks thereafter on days 1 and 15.

The recommended dose of lenalidomide is 25 mg orally once daily on days 1-21 of repeated 28-day cycles, and at least 2 hours after Empliciti infusion when administered on the same day. The administration of dexamethasone is as follows: ▪ On days that Empliciti is administered, dexamethasone should be given as 28 mg orally once daily between 3 and 24 hours before Empliciti plus 8 mg intravenously between 45 and 90 minutes before Empliciti on days 1, 8, 15, and 22 of repeated 28-day cycles.

▪ On days that Empliciti is not administered but a dose of dexamethasone is scheduled (Days 8 and 22 of cycle 3 and all subsequent cycles), dexamethasone should be given 40 mg orally.

Table 1:

Recommended dosing schedule of Empliciti in combination with lenalidomide and dexamethasone Cycle 28-Day Cycles 1 & 2 28-Day Cycles 3+ Day of Cycle 1 8 15 22 1 8 15 22 Premedication ✓ ✓ ✓ ✓ ✓ ✓ Empliciti (mg/kg bw) intravenously 10 10 10 10 10 10 Lenalidomide (25 mg) orally Days 1-21 Days 1-21 Dexamethasone (mg) orally 28 28 28 28 28 40 28 40 Day of Cycle 1 8 15 22 1 8 15 22 For additional information concerning lenalidomide and dexamethasone, see the corresponding Summary of Product Characteristics.

Summary of safety profile The safety data of elotuzumab have been assessed from a total of 682 patients with multiple myeloma treated with elotuzumab in combination with lenalidomide and dexamethasone (451 patients), bortezomib and dexamethasone (103 patients) or pomalidomide and dexamethasone (128 patients) pooled across 8 clinical trials.

The majority of adverse reactions were mild to moderate (Grade 1 or 2). The most serious adverse reaction that may occur during elotuzumab treatment is pneumonia. The most common adverse reactions (occurring in > 10% of patients) with elotuzumab treatment were IRRs, diarrhoea, herpes zoster, nasopharyngitis, cough, pneumonia, upper respiratory tract infection, lymphopenia and weight decreased.

8 Tabulated list of adverse reactions Adverse reactions reported in 682 patients with multiple myeloma who were treated with elotuzumab in 8 clinical trials are presented in Table

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. 8). 2 Premedication). The rate of IRRs was much higher in patients who were not premedicated.

If any of the symptoms of IRR reach Grade ≥ 2, Empliciti infusion must be interrupted and appropriate medical and supportive measures instituted. Vital signs should be monitored every 30 minutes for 2 hours after the end of the Empliciti infusion.

5 mL/min. 2 Method of administration). Very severe IRRs may require permanent discontinuation of Empliciti therapy and emergency treatment. 2 Method of administration). Conditions for use of medicinal products used with Empliciti Empliciti is used in combination with other medicinal products; therefore, the conditions for use applicable to those medicinal products also apply to the combination therapy.

The Summary of Product Characteristics for all medicinal products used in combination with Empliciti must be consulted before starting therapy. 8). Patients should be monitored and infections should be managed with standard treatment.

8). SPMs are known to be associated with lenalidomide exposure, which was extended in patients treated with Empliciti combined with lenalidomide and dexamethasone vs. lenalidomide and dexamethasone. The rate of haematologic malignancies was the same between the two treatment arms.

Patients should be monitored for the development of SPMs. 3% respectively, of the WHO recommended maximum daily intake of 2 g sodium for an adult.

1. The Summary of Product Characteristics for lenalidomide, pomalidomide and dexamethasone used in combination with Empliciti must be consulted before starting therapy.