Multiple myeloma

Elotuzumab therapy should be initiated and supervised by physicians experienced in the treatment of multiple myeloma.

Premedication for prevention of infusion reaction

Patients must be administered with the following premedications 45-90 minutes prior to elotuzumab infusion:

• 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 infusion reaction

If a ≥ Grade 2 infusion reaction occurs during elotuzumab administration, the infusion must be interrupted. Upon resolution to ≤ Grade 1, elotuzumab should be restarted at 0.5 mL/min and may be gradually increased at a rate of 0.5 mL/min every 30 minutes as tolerated to the rate at which the infusion reaction occurred. If there is no recurrence of the infusion reaction, the escalation can be resumed.

In patients who experience an infusion reaction, vital signs should be monitored every 30 minutes for 2 hours after the end of the elotuzumab infusion. If the infusion reaction recurs, the elotuzumab infusion must be stopped and not restarted on that day. Very severe infusion reactions (≥ Grade 3) may require permanent discontinuation of elotuzumab 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 elotuzumab is 10 mg/kg 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 elotuzumab infusion when administered on the same day.

The administration of dexamethasone is as follows:

• On days that elotuzumab is administered, dexamethasone should be given as 28 mg orally once daily between 3 and 24 hours before elotuzumab plus 8 mg intravenously between 45 and 90 minutes before elotuzumab on days 1, 8, 15, and 22 of repeated 28-day cycles.
• On days that elotuzumab 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 elotuzumab in combination with lenalidomide and dexamethasone:

Posology for administration with pomalidomide and dexamethasone

The length of each treatment cycle is 28 days, see Table 2 for the dosing schedule. Treatment should continue until disease progression or unacceptable toxicity.

The recommended dose of elotuzumab is 10 mg/kg administered intravenously every week on days 1, 8, 15, and 22 of each treatment cycle for the first two cycles and then 20 mg/kg administered on day 1 of each treatment cycle thereafter.

The recommended dose of pomalidomide is 4 mg orally once daily on days 1-21 of repeated 28-day cycles, and at least 2 hours after elotuzumab infusion when administered on the same day.

The administration of dexamethasone is as follows:

• On days that elotuzumab is administered, patients ≤75 years old give dexamethasone 28 mg orally between 3 and 24 hours before elotuzumab plus 8 mg intravenously between 45 and 90 minutes before elotuzumab and for patients >75 years old give dexamethasone 8 mg orally between 3 and 24 hours before elotuzumab plus 8 mg intravenously between 45 and 90 minutes before elotuzumab.
• On days that elotuzumab is not administered but a dose of dexamethasone is scheduled (Days 8, 15 and 22 of cycle 3 and all subsequent cycles), give 40 mg orally to patients ≤75 years old and 20 mg orally to patients >75 years old.

Table 2. Recommended dosing schedule of elotuzumab in combination with pomalidomide and dexamethasone:

Dose delay, interruption, or discontinuation

If the dose of one medicine in the regimen is delayed, interrupted, or discontinued, the treatment with the other medicinal products may continue as scheduled. However, if oral or intravenous dexamethasone is delayed or discontinued, the administration of elotuzumab should be based on clinical judgment (e.g. risk of hypersensitivity).

Elotuzumab is for intravenous use only.

Infusion rate for elotuzumab 10 mg/kg

The administration of the reconstituted and diluted solution must be initiated at an infusion rate of 0.5 mL/min. If the infusion is well tolerated the infusion rate may be increased in a stepwise fashion as described in the following table. The maximum infusion rate should not exceed 5 mL/min.

Infusion rate for elotuzumab 10 mg/kg:

* Continue this rate until infusion is completed.

Infusion rate for elotuzumab 20 mg/kg

The administration of reconstituted and diluted solution must be initiated at an infusion rate of 3 mL/min. If the infusion is well tolerated, the infusion rate maybe increased in a stepwise fashion as described in the table below. The maximum infusion rate should not exceed 5 mL/min. Patients who have escalated to 5 mL/min at 10 mg/kg dose must decrease the rate to 3 mL/min at the first infusion at 20 mg/kg.

Infusion rate for elotuzumab 20 mg/kg:

* Continue this rate until infusion is completed.