Elotuzumab is a monoclonal antibody medication used in the treatment of multiple myeloma, a type of cancer that affects plasma cells in the bone marrow. It is often prescribed in combination with other medications, typically lenalidomide and dexamethasone, for patients who have relapsed or are refractory to previous treatments.

Elotuzumab works by targeting a protein called SLAMF7 (Signaling Lymphocytic Activation Molecule Family member 7), also known as CS1 (CD2 subset 1) or CD319, which is present on the surface of myeloma cells. By binding to SLAMF7, elotuzumab helps activate the body's immune system to attack and kill the cancer cells.

Elotuzumab (Empliciti) is a humanized IgG1 immunostimulatory monoclonal antibody directed against the SLAMF7 molecule family (as per the Elotuzumab Package Insert). SLAMF7 molecules (signaling lymphocytic activation molecule family member 7) are present in most myeloma and natural killer cells but not on normal tissue cells.

Elotuzumab (Empliciti) Uses:

• Relapsed/ refractory Multiple Myeloma:
  • Treatment of multiple myeloma (in combination with lenalidomide and dexamethasone) among those patients who have received 1 to 3 prior therapies;
  • Treatment of multiple myeloma (in combination with pomalidomide and dexamethasone) in patients who have received at least 2 prior therapies, catering lenalidomide, and a proteasome inhibitor (Ixazomib, Carfilzomib).

Elotuzumab Dose in Adults:

Note:

• Before you receive elotuzumab, your healthcare provider will give you some other medicines to help prevent side effects.
• These medicines include dexamethasone (a steroid), an H-blocker like diphenhydramine, another H-blocker like ranitidine, and acetaminophen (like Tylenol).
• You'll take these medicines about 45 to 90 minutes before you get the elotuzumab infusion.

Elotuzumab (Empliciti) Dose in the treatment of relapsed or refractory Multiple Myeloma: IV: 

Continue its use until disease progression or unacceptable toxicity

In combination with lenalidomide and dexamethasone:

• Cycles 1 and 2: You'll receive Elotuzumab at a dose of 10 mg/kg once weekly on days 1, 8, 15, and 22 of a 28-day treatment cycle, along with lenalidomide and dexamethasone.
• Cycle 3 and beyond: The dose of Elotuzumab changes to 10 mg/kg once every 2 weeks on days 1 and 15 of a 28-day treatment cycle, still in combination with lenalidomide and dexamethasone.

In combination with pomalidomide and dexamethasone:

• Cycles 1 and 2: You'll receive Elotuzumab at a dose of 10 mg/kg once weekly on days 1, 8, 15, and 22 of a 28-day treatment cycle, along with pomalidomide and dexamethasone.
• Cycle 3 and beyond: The dose of Elotuzumab changes to 20 mg/kg once every 4 weeks on day 1 of a 28-day treatment cycle, still in combination with pomalidomide and dexamethasone.

In addition to Elotuzumab, you'll also be given premedications to help manage potential side effects:

• Dexamethasone: The dose of dexamethasone differs based on the chemotherapy regimen you're on. It's administered orally and intravenously.
  • On days when Elotuzumab is given, you'll typically take dexamethasone 28 mg orally 3 to 24 hours before Elotuzumab infusion, and dexamethasone 8 mg intravenously 45 to 90 minutes before the infusion.
  • On days when Elotuzumab is not administered but dexamethasone is scheduled (e.g., days 8 and 22 of cycle 3 and beyond), you'll usually take the standard dexamethasone dose, which is 40 mg orally.
  • There's also an option of a one-time dexamethasone dose of 20 to 40 mg intravenously on days when Elotuzumab is given if compliance with oral and IV dexamethasone is a concern.
• Antipyretic: You'll be given acetaminophen (650 to 1,000 mg) orally to help manage fever or discomfort.
• H-blocker: To prevent allergic reactions, you'll receive an H-blocker like diphenhydramine (25 to 50 mg or equivalent) either intravenously or orally.
• H-blocker (alternative): Instead of diphenhydramine, ranitidine (50 mg IV or 150 mg orally or equivalent) can be used. In some cases, famotidine 20 mg IV has also been reported as an alternative.

Use in Children:

Not indicated. 

Elotuzumab (Empliciti) Pregnancy Risk Category: X

• Elotuzumab has not undergone animal reproduction studies.
• It is used in combination with lenalidomide or pomalidomide, both of which have the potential to cause harm to a developing fetus.
• Because of this risk, these medications are only available through a Risk Evaluation and Mitigation Strategy (REMS) program.
• If you are a male or female of reproductive potential and are considering using these combinations of medications, you must be willing and able to follow certain requirements related to pregnancy testing and contraception.
• These requirements are put in place to minimize the risk of pregnancy while taking lenalidomide or pomalidomide, as they can harm a developing baby.
• For more detailed information about these requirements and the specific precautions to take when using lenalidomide or pomalidomide, you should refer to the individual monographs or prescribing information for each of these medications.

Use of Elotuzumab while breastfeeding

• The presence of elotuzumab in breast milk is not known, and because of the potential for serious adverse reactions in a breastfed infant, the manufacturer does not recommend breastfeeding while using this medication.
• It is important to prioritize the safety of both the mother and the baby, so if you are considering using elotuzumab or are currently receiving this treatment.

Elotuzumab (Empliciti) Dose in Kidney disease:

• For individuals with a creatinine clearance (CrCl) of less than or equal to 89 mL/minute, the manufacturer's labeling for elotuzumab typically does not specify dosage adjustments. However, based on pharmacokinetics (how the drug is processed in the body), it is generally considered that dosage adjustment is not likely to be necessary in this case.

Elotuzumab (Empliciti) Dose in Liver disease:

Hepatic Impairment Prior to Treatment:

• Mild Hepatic Impairment:
  • If a patient has mild hepatic impairment (defined as total bilirubin within the normal range or slightly elevated and elevated AST), the manufacturer's labeling typically does not provide specific dosage adjustments. However, it is generally believed, based on pharmacokinetics (how the drug is processed in the body), that dosage adjustment is unlikely to be necessary in this case.
• Moderate to Severe Hepatic Impairment:
  • For patients with moderate (total bilirubin >1.5 to 3 times the upper limit of normal) to severe (total bilirubin >3 times the upper limit of normal) hepatic impairment, the manufacturer's labeling does not provide dosage adjustments. It's important to note that elotuzumab's use in patients with these levels of hepatic impairment has not been studied extensively.

Hepatotoxicity During Treatment:

• If a patient experiences Grade 3 or higher elevations in liver transaminase levels (AST or ALT) during elotuzumab treatment, the manufacturer recommends withholding further treatment. Depending on the clinical situation and after liver enzyme levels have returned to baseline, healthcare providers may consider resuming treatment cautiously.

Side effects:

All incidences reported with combination therapy.

Common Side Effects of Elotuzumab (Empliciti):

• Cardiovascular:
  • Decreased Heart Rate
  • Increased Heart Rate
  • Altered Blood Pressure
  • Peripheral Edema
• Central Nervous System:
  • Fatigue
  • Peripheral Neuropathy
  • Headache
• Endocrine & Metabolic:
  • Hyperglycemia
  • Hypocalcemia
  • Hypoalbuminemia
  • Decreased Serum Bicarbonate
  • Hyponatremia
  • Hyperkalemia
  • Hypokalemia
  • Weight Loss
• Gastrointestinal:
  • Diarrhea
  • Constipation
  • Decreased Appetite
  • Vomiting
• Hematologic & Oncologic:
  • Lymphocytopenia
  • Leukopenia
  • Thrombocytopenia
• Hepatic:
  • Increased Serum Alkaline Phosphatase
• Immunologic:
  • Antibody Development
• Infection:
  • Infection
  • Opportunistic Infection
  • Herpes Zoster Infection
  • Fungal Infection
• Neuromuscular & Skeletal:
  • Limb Pain
  • Ostealgia
  • Muscle Spasm
• Ophthalmic:
  • Cataract
• Respiratory:
  • Cough
  • Nasopharyngitis
  • Upper Respiratory Tract Infection
  • Pneumonia
  • Respiratory Tract Infection
  • Dyspnea
  • Oropharyngeal Pain
• Miscellaneous:
  • Fever
  • Infusion Related Reaction

Less Common Side Effects Of Elotuzumab (Empliciti):

• Cardiovascular:
  • Chest Pain
  • Pulmonary Embolism
• Central Nervous System:
  • Hypoesthesia
  • Mood Changes
• Dermatologic:
  • Night Sweats
• Hematologic & Oncologic:
  • Second Primary Malignant Neoplasm
  • Malignant Neoplasm Of Skin
  • Malignant Solid Tumor
  • Anemia
  • Malignant Neoplasm
• Hepatic:
  • Hepatotoxicity
• Hypersensitivity:
  • Hypersensitivity Reaction
• Renal:
  • Acute Renal Failure

Contraindications to Elotuzumab (Empliciti):

In the United States, the manufacturer's labeling for elotuzumab does not list any specific contraindications, which means there are no absolute reasons stated in the labeling where the use of elotuzumab is prohibited.

However, it's crucial for healthcare providers to carefully assess each patient's individual medical history, allergies, and potential hypersensitivity reactions when considering the use of elotuzumab. If a patient has a known hypersensitivity or allergy to elotuzumab or any component of the formulation, it may be a valid reason to avoid its use.

In the Canadian labeling, it explicitly mentions hypersensitivity to elotuzumab or any component of the formulation as a contraindication, indicating that elotuzumab should not be used in individuals with a known hypersensitivity or allergy to the drug or its ingredients.

Warnings and precautions

Hepatotoxicity

• Hepatotoxicity means that there can be problems with your liver when taking this medication.
• It might show up as increased levels of certain substances in your blood: AST/ALT more than 3 times the normal limit, total bilirubin more than 2 times the normal limit, and alkaline phosphatase less than 2 times the normal limit.
• To keep an eye on your liver, your healthcare provider will check your liver function regularly while you're on this medication.
• If there are concerning changes in these tests, it might be necessary to temporarily stop or even completely discontinue the treatment to protect your liver.

Infection

• Infections, some of them severe (grade 3 and 4), were common among people with multiple myeloma who received this treatment during clinical trials, and some of these infections were fatal.
• While you're on this therapy, your healthcare team will keep an eye out for different types of infections, including ones that can happen when your immune system is weak, like fungal and herpes zoster infections.
• If you do get an infection, they will treat it promptly to keep you safe.

Infusion reactions

• During the infusion of this medication, some people may experience infusion reactions like fever, chills, and high blood pressure, but these reactions are usually not severe (grade 3 or lower).
• Sometimes, during the infusion, people might also have bradycardia (slow heart rate) or low blood pressure.
• Most of these infusion reactions, about 70%, happen during the first dose.
• To help prevent these reactions, you'll receive premedications like dexamethasone, H-blockers, and H-blockers, as well as acetaminophen, before each dose.
• Your treatment should be given in a place where they can quickly provide emergency treatments like steroids, epinephrine, bronchodilators, and oxygen if needed.

Secondary malignancy

• There have been reports of new cancers developing in people who used this medication.
• In one study, the rate of blood-related cancers was similar between those who took elotuzumab with lenalidomide and dexamethasone and those who took only lenalidomide and dexamethasone.
• However, solid tumors and skin cancer were more common in the group that received elotuzumab.
• So, your healthcare provider will keep an eye out for any signs of new cancers while you're on this treatment.

Interference with determination of myeloma response

• Elotuzumab, which is a type of antibody used in treatment, can show up on certain blood tests called serum protein electrophoresis and immunofixation assays.
• These tests are used to monitor a substance called M-protein in the blood, which is important in myeloma.
• However, elotuzumab can interfere with these tests and make it tricky to accurately measure M-protein.
• This interference might affect the diagnosis of complete response or disease progression in some patients who have a specific type of myeloma called IgG kappa myeloma protein.

Elotuzumab: Drug Interaction

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

Liver Function Tests:

• Periodic monitoring of liver function tests is necessary during treatment.

Infusion Reactions:

• Keep a close eye on signs and symptoms of infusion reactions.
• For patients who experience an infusion reaction, monitor vital signs every 30 minutes during the infusion and for 2 hours after it ends.

Infections:

• Watch out for any signs of infection, and report them to your healthcare provider.

Second Primary Malignancies:

• Be aware of the development of any new cancers or unusual symptoms.

How to administer Elotuzumab (Empliciti)?

Preparation and Precautions:

• This medication should only be administered through IV infusion, not as a quick injection.
• Before the infusion, premedicate with dexamethasone, acetaminophen, and an H-blocker and H-blocker approximately 45 to 90 minutes before.
• Infuse the medication in an environment where they can monitor and manage infusion reactions.
• Use an infusion set and a sterile, non-pyrogenic, low protein-binding filter with a size of 0.2 to 1.2 micrometers.
• Do not mix this medication with or infuse it with other medications.
• The infusion should be completed within 24 hours of reconstitution.

Monitoring:

• Keep a close eye on the patient for any signs of infusion reactions.
• In case of grade 2 or higher infusion reactions, interrupt the infusion.
• If the reaction improves to ≤ grade 1, you may resume the infusion (see Dosage Adjustment for Toxicity).
• Monitor vital signs every 30 minutes during and for 2 hours after the end of the infusion in patients who experience an infusion reaction.

Infusion Rates:

• The infusion rate varies depending on the dose and whether it's the first or subsequent infusion:
  • For a 10 mg/kg dose:
    • First infusion (Cycle 1, Dose 1): Start at 0.5 mL/minute for the first 30 minutes and may increase if tolerated.
    • Second infusion (Cycle 1, Dose 2): Initiate at 3 mL/minute and increase if tolerated.
    • Subsequent infusions (Cycle 1, Doses 3 and 4 and all subsequent infusions): Initiate at 5 mL/minute if no previous infusion reactions occurred.
  • For a 20 mg/kg dose:
    • First infusion (Dose 1): Start at 3 mL/minute, and if tolerated, may increase.
    • Second infusion (Dose 2): Initiate and infuse at 5 mL/minute.

Mechanism of action of Elotuzumab (Empliciti):

• Elotuzumab is a type of medication known as a humanized IgG1 immunostimulatory monoclonal antibody.
• It's designed to target a specific protein called SLAMF7, which is also known as CS1 (cell surface glycoprotein CD2 subset 1).
• SLAMF7 is found on most myeloma cells (a type of cancer cell) and natural killer cells, but it's not typically found on healthy tissues.
• In fact, more than 95% of myeloma cells in the bone marrow express SLAMF7.
• Elotuzumab works in a couple of ways.
• It directly activates natural killer cells, which are a part of the immune system, by interacting with the SLAMF7 pathway and Fc receptors.
• Additionally, it targets SLAMF7 on myeloma cells and helps the immune system destroy these cancer cells through a process called antibody-dependent cellular cytotoxicity (ADCC) via the CD16 pathway.
• This immune-stimulating activity helps increase the body's ability to fight against the cancer, making it a valuable treatment for multiple myeloma.

Eliminating half-life

• The half-life elimination of a medication refers to the time it takes for approximately half of the drug to be cleared from the body.
• In the case of elotuzumab, around 97% of the maximum steady-state concentration (the amount of the drug in the body when it's reached a consistent level) is expected to be eliminated with an average half-life of approximately 78 to 82.4 days.
• This means that it takes this amount of time for the concentration of elotuzumab in the body to decrease by half.
• The specific half-life for an individual may vary, but this range provides a general idea of how long it takes for the medication to be removed from the body.

International Brand Names of Elotuzumab:

• Empliciti

Elotuzumab Brand Names in Pakistan:

Not available.