Elotuzumab – Uses, Dosage, Side Effects, Interaction

Mechanism of action

Elotuzumab is a humanized IgG1 monoclonal antibody that specifically targets the SLAMF7 (Signaling Lymphocytic Activation Molecule Family member 7) protein. SLAMF7 is expressed on myeloma cells independent of cytogenetic abnormalities. SLAMF7 is also expressed on Natural Killer cells, plasma cells, and at lower levels on specific immune cell subsets of differentiated cells within the hematopoietic lineage. Elotuzumab directly activates Natural Killer cells through both the SLAMF7 pathway and Fc receptors. Elotuzumab also targets SLAMF7 on myeloma cells and facilitates the interaction with Natural Killer cells to mediate the killing of myeloma cells through antibody-dependent cellular cytotoxicity (ADCC). In preclinical models, the combination of elotuzumab and lenalidomide resulted in enhanced activation of Natural Killer cells that was greater than the effects of either agent alone and increased anti-tumor? activity in vitro and in vivo.

Elotuzumab is a humanized IgG1 monoclonal antibody that specifically targets the SLAMF7 (Signaling Lymphocytic Activation Molecule Family member 7) protein. SLAMF7 is expressed on myeloma cells independent of cytogenetic abnormalities. SLAMF7 is also expressed on
Natural Killer cells, plasma cells, and at lower levels on specific immune cell subsets of differentiated cells within the hematopoietic lineage. Elotuzumab directly activates Natural Killer cells through both the SLAMF7 pathway and Fc receptors. Elotuzumab also targets SLAMF7 on myeloma cells and facilitates the interaction with Natural Killer cells to mediate the killing of myeloma cells through antibody-dependent
cellular cytotoxicity (ADCC). In preclinical models, the combination of elotuzumab and lenalidomide resulted in enhanced activation of Natural Killer cells that was greater than the effects of either agent alone and increased anti-tumor activity in vitro and in vivo.

Indications

• Indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received one to three prior therapies.
• Refractory Multiple Myeloma

Contraindications

• shingles
• a bad infection?
• abnormal liver? function tests
• pregnancy
• a patient who is producing milk and breastfeeding

Dosage?

Strengths: 300 mg; 400 mg

Multiple Myeloma

IN COMBINATION WITH LENALIDOMIDE AND DEXAMETHASONE:

• Cycles 1 and 2: 10 mg/kg IV once a week on Days 1, 8, 15, and 22 of a 28-day cycle
• Cycle 3 and beyond: 10 mg/kg IV once every 2 weeks on Days 1 and 15 of a 28-day cycle until disease progression? or unacceptable toxicity

PREMEDICATION:
(Note: Dexamethasone dosing differs depending on the chemotherapy? regimen):

• Patients should be premedicated 45 to 90 minutes before administration of elotuzumab with dexamethasone 8 mg IV, an H1 blocker (e.g., diphenhydramine 25 to 50 mg IV or orally or equivalent); an H2 blocker (e.g., ranitidine 50 mg IV or equivalent), and acetaminophen 650 to 1000 mg orally.
• On days that elotuzumab is administered, give dexamethasone 28 mg orally 3 to 24 hours before elotuzumab (in addition to the dexamethasone 8 mg IV 45 to 90 minutes prior to elotuzumab).
• On days that elotuzumab is not administered but dexamethasone is scheduled (Days 8 and 22 of Cycle 3 and beyond) give dexamethasone 40 mg orally.

IN COMBINATION WITH POMALIDOMIDE AND DEXAMETHASONE:

• Cycles 1 and 2: 10 mg/kg IV once a week on Days 1, 8, 15, and 22 of a 28-day cycle
• Cycle 3 and beyond: 20 mg/kg IV once every 4 weeks on Day 1 of a 28-day cycle until disease progression? or unacceptable toxicity

PREMEDICATION:
(Note: Dexamethasone dosing differs depending on the chemotherapy regimen):

• Patients should be premedicated 45 to 90 minutes before administration of elotuzumab with dexamethasone 8 mg IV, an H1 blocker (e.g., diphenhydramine 25 to 50 mg IV or orally or equivalent); an H2 blocker (e.g., ranitidine 50 mg IV or equivalent), and acetaminophen 650 to 1000 mg orally.

ADMINISTER DEXAMETHASONE AS FOLLOWS:
75 YEARS AND YOUNGER:

• On days that elotuzumab is administered, give dexamethasone 28 mg orally between 3 and 24 hours before elotuzumab (in addition to the dexamethasone 8 mg IV between 45 and 90 minutes before elotuzumab).
• 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), give 40 mg orally.

OLDER THAN 75 YEARS:

• On days that elotuzumab is administered, give dexamethasone 8 mg orally 3 to 24 hours before elotuzumab (in addition to the dexamethasone 8 mg IV 45 to 90 minutes prior to elotuzumab).
• On days that elotuzumab is not administered but dexamethasone is scheduled (Days 8 and 22 of Cycle 3 and beyond) give dexamethasone 20 mg orally.

Manufacturer recommended infusion rate for 10 mg/kg dose:
CYCLE 1, DOSE 1:

• Time interval 0 to 30 min: Rate 0.5 mL/min
• Time interval 30 to 60 min: Rate 1 mL/min
• Time interval 60 min or more: Rate 2 mL/min

CYCLE 1, DOSE 2:

• Time interval 0 to 30 min: Rate 3 mL/min
• Time interval 30 min or more: Rate 4 mL/min

CYCLE 1, DOSE 3 AND 4 AND ALL SUBSEQUENT CYCLES:

• Time interval 30 to 60 min: Rate 5 mL/min

Manufacturer recommended infusion rate for 20 mg/kg dose (patients who 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):
DOSE 1:

• Time interval 0 to 30 min: Rate 3 mL/min
• Time interval 30 min or more: Rate 4 mL/min

DOSE 2 AND ALL SUBSEQUENT DOSES:

• Time interval 30 min or more: Rate 5 mL/min
• Refer to the dexamethasone, lenalidomide, and pomalidomide prescribing information for additional information.
• In combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received 1 to 3 prior therapies
• In combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least 5 prior therapies including lenalidomide and a proteasome inhibitor

Dose Adjustments

• If the dose of one drug in the regimen is delayed, interrupted, or discontinued, the treatment with the other drugs may continue as scheduled; however, if dexamethasone is delayed or discontinued, the decision on whether to administer elotuzumab should be based on clinical? judgment (i.e., risk of hypersensitivity).
• If a Grade 2 or higher infusion reaction occurs, interrupt the infusion and institute appropriate medical measures. Upon resolution to Grade 1 or lower, restart elotuzumab at 0.5 mL per minute and gradually increase at a rate of 0.5 mL per minute every 30 minutes as tolerated to the rate at which the infusion reaction occurred. Resume the escalation regimen if there is no recurrence? of the infusion reaction.
• For patients who experience an infusion reaction, monitor vital signs? every 30 minutes during and for 2 hours after the end of the infusion in patients who experience an infusion reaction. If the reaction recurs, stop the infusion and do not restart on that day. Severe? infusion reactions may require permanent discontinuation of therapy and emergency? treatment.
• Dose delays and modifications for dexamethasone, pomalidomide, and lenalidomide should be performed as recommended in their Prescribing Information.

Side Effects

The Most Common

• diarrhea?
• constipation?
• headache?
• vomiting?
• mood changes
• weight loss?
• night sweats?
• numbness? or decreased sense of touch
• bone pain?
• muscle spasms
• Blindness
• burning, numbness, tingling?, or painful sensations
• decreased appetite
• decreased vision
• decreased weight
• diarrhea
• difficulty having a bowel movement
• muscle aches
• night sweats
• pain? in the arms or legs
• unsteadiness or awkwardness
• weakness? in the arms, hands, legs, or feet
• swelling? of your arms or legs
• chills?, sore throat, fever, or cough; shortness of breath; pain or burning upon urination; painful rash; or other signs of infection
• numbness, weakness, tingling, or burning pain in your arms or legs
• chest pain
• nausea, extreme tiredness and lack of energy, loss of appetite, yellowing of the skin or eyes, dark urine, pale stools, confusion, pain in the upper right part of the stomach
• vision changes

More common

• Blurred vision
• body aches or pain
• chest pain
• chills
• clay-colored stools
• confusion
• cough
• dark urine
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• ear congestion
• fever
• headache
• hives, itching, skin rash
• hoarseness
• irritation
• joint pain, stiffness, or swelling
• loss of appetite
• loss of voice
• lower back or side pain
• nasal congestion
• nausea
• nervousness
• painful or difficult urination
• persistent sore that does not heal
• pink skin growth
• pounding in the ears
• reddish patch or irritated area
• redness of the skin
• runny nose
• shiny skin bump
• slow or fast heartbeat
• sneezing
• sore throat
• stomach pain or tenderness
• stuffy nose
• sweating
• swelling of the eyelids, face, lips, hands, or feet
• tightness in the chest
• troubled breathing or swallowing
• unusual tiredness or weakness
• vomiting
• white, yellow or waxy scar-like area on the skin
• yellow eyes or skin

Rare

• Agitation
• anxiety
• decreased awareness or responsiveness
• decreased urine output
• depression
• dizziness or lightheadedness
• fainting
• fast heartbeat
• hostility
• irritability
• loss of consciousness
• muscle twitching
• pale skin
• rapid weight gain
• seizures
• severe sleepiness
• troubled breathing with exertion
• unusual bleeding or bruising
• unusual drowsiness, dullness, or feeling of sluggishness

Drug interaction

Pregnancy and Lactation

AU TGA pregnancy category: C
US FDA pregnancy category: Not assigned

Pregnancy

There are no studies with EMPLICITI with pregnant women to inform of any drug-associated risks. Animal reproduction studies have not been conducted with elotuzumab. EMPLICITI is administered in combination with lenalidomide and dexamethasone. Lenalidomide can cause embryo-fetal harm and is contraindicated for use in pregnancy. Refer to the lenalidomide and dexamethasone prescribing information for additional information. Lenalidomide is only available through a REMS program. The background risk in the U.S. general population of major birth defects is 2% to 4% and miscarriage is 15% to 20% of clinically recognized pregnancies.

Lactation

There is no information on the presence of EMPLICITI in human milk, the effect on the breastfed infant, or the effect on milk production. Because of the potential for serious adverse reactions in breastfed infants from elotuzumab administered with lenalidomide/dexamethasone, breastfeeding is not recommended. Refer to the lenalidomide and dexamethasone prescribing information for additional information.

References