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).

Adult dose:

Note:

• Premedicate with dexamethasone, an H-1 blocker (e.g.diphenhydramine), an H-2 blocker (e.g.ranitidine), and acetaminophen ~45 to 90 minutes before infusion (see Premedications below).
• However, for dosing information refer to the lenalidomide, pomalidomide, and dexamethasone monographs.

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:
    • 10 mg/kg once a week on days 1, 8, 15, and 22 of a 28-day treatment cycle (in combination with lenalidomide and dexamethasone)
  • Cycle 3 and beyond:
    • 10 mg/kg once every 2 weeks on days 1 and 15 of a 28-day treatment cycle (in combination with lenalidomide and dexamethasone)

• In combination with pomalidomide and dexamethasone:

  • Cycles 1 and 2:
    • 10 mg/kg once on a weekly basis on days 1, 8, 15, and 22 of a 28-day treatment cycle (in combination with pomalidomide and dexamethasone)
  • Cycle 3 and beyond:
    • 20 mg/kg once every 4 weeks on day 1 of a 28-day treatment cycle (in combination with pomalidomide and dexamethasone)

Premedications:

• Dexamethasone: Oral and IV:

Note: Dexamethasone dosing differs depending on the chemotherapy regimen.

• • Elotuzumab/ lenalidomide/ dexamethasone regimen:

    • On days that elotuzumab is administered, give dexamethasone 28 mg orally 3 to 24 hours before elotuzumab infusion plus dexamethasone 8 mg IV 45 to 90 minutes earlier to infusion.
    • However, on days that elotuzumab is not administered but dexamethasone is due (e.g. days 8 and 22 of cycle 3 and beyond), administer the standard dexamethasone dose (40 mg orally).
    • Because of compliance concerns on days that elotuzumab is administered, a one-time dexamethasone dose of 20 to 40 mg IV has been reported (in lieu of administering both oral and IV dexamethasone).

  • Elotuzumab/ pomalidomide/ dexamethasone regimen:

    • Patients ≤75 years:
      • On days that elotuzumab is administered, give dexamethasone 28 mg orally 3 to 24 hours before elotuzumab infusion plus dexamethasone 8 mg IV 45 to 90 minutes before infusion.
      • On days that elotuzumab is not administered but dexamethasone is due (e.g. days 8, 15, and 22 of cycle 3 and beyond), administer dexamethasone 40 mg orally.
    • Patients >75 years:
      • On days that elotuzumab is administered, give dexamethasone 8 mg orally 3 to 24 hours before elotuzumab infusion plus dexamethasone 8 mg IV 45 to 90 minutes prior to infusion.
      • Though, on days that elotuzumab is not administered but dexamethasone is due (e.g. days 8, 15, and 22 of cycle 3 and beyond), administer dexamethasone 20 mg orally.

• Antipyretic:

  • Oral Acetaminophen 650 to 1,000 mg

• H-1 blocker:

  • IV or Oral Diphenhydramine 25 to 50 mg or equivalent

• H-2 blocker:

  • Ranitidine 50 mg IV or 150 mg orally or equivalent.
  • The use of famotidine 20 mg IV has also been reported.

Use in Children:

Not indicated. 

Elotuzumab (Empliciti) Pregnancy Risk Category: X

• • There have not been any studies on animal reproduction.
  • Elotuzumab can be used in combination with lenalidomide and pomalidomide.
  • Due to its potential for fetal harm, lenalidomide/pomalidomide can only be obtained through a REMS program.
  • These combinations are suitable for both male and female reproductive potential.
  • For more information, refer to the lenalidomide/pomalidomide monograph.

  Use of Elotuzumab while breastfeeding

  • It is not known if elotuzumab may be present in breast milk.
  • Manufacturers do not recommend breastfeeding due to the risk of serious adverse reactions in infants who are breastfed.

Elotuzumab (Empliciti) Dose in Kidney disease:

• CrCl ≤89 mL/minute:

  • No dosage adjustments provided in the manufacturer's labeling; however, based on pharmacokinetics, dosage adjustment is not likely necessary.

Elotuzumab (Empliciti) Dose in Liver disease:

• Hepatic impairment prior to treatment:

  • Mild (total bilirubin ≤ULN and AST >ULN or total bilirubin 1 to 1.5 times ULN and any AST) impairment:
    • No dosage adjustments are provided in the manufacturer's labeling; however, based on pharmacokinetics, dosage adjustment is not likely necessary.
  • Moderate (total bilirubin >1.5 to 3 times ULN and any AST) to severe (total bilirubin >3 times ULN and any AST) impairment:
    • No dosage adjustments are provided in the manufacturer's labeling (has not been studied).

• Hepatotoxicity during treatment:

  • Grade 3 or higher transaminase elevations:
    • Withhold treatment; it may consider continuing treatment after liver enzymes return to baseline.

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):

• • • The US labeling of the manufacturer does not contain any contraindications.

Canadian labeling

• • • Hypersensitivity to elotuzumab and any component of the formula

Warnings and precautions

• • Hepatotoxicity

    • Liver enzyme elevations have been observed (AST/ALT greater than 3x ULN; total bilirubin greater than 2x ULN; and alkalinephosphatase less that 2x ULN).
    • Regularly monitor liver function tests; treatment interruption or discontinuation may be necessary.

  • Infection

    • Multiple myeloma patients who were treated in clinical trials had infected (including grade 3 or 4 infections), which included fatal infections.
    • During therapy, monitor for possible opportunistic, fungal or herpes zoster infections. However, it is important to treat any infections promptly.

  • Infusion reactions

    • Infusion reactions (e.g. Infusion reactions (e.g., fever, chills and hypertension) were reported. All reactions were grade 3 or below. However, infusions can also cause bradycardia or hypotension.
    • Most infusion reactions (70%) occurred within the first dose.
    • Before each dose, take dexamethasone and H-1 and H-2 blocking drugs. Acetaminophen should also be taken.
    • In a place with immediate access to resuscitative actions (e.g. glucocorticoids epinephrine and bronchodilators (and/or oxygen) should be administered in a facility with immediate access to resuscitative measures (e.g.
    • It could require treatment interruption, modification of the infusion rate, or discontinuation.

  • Secondary malignancy

    • We have identified two primary and invasive malignancies.
    • In one clinical trial, the rate of hematologic malignancies in the elotuzumab/ dexamethasone and lenalidomide/dexamethasone groups was identical.
    • The elotuzumab group was more likely to have skin cancer and solid tumors than the control. However, you should be vigilant for secondary malignancies.

  • Interference with determination of myeloma response

    • Elotuzumab, a monoclonal human IgG kappa antibody, can be detected by serum protein electrophoresis or immunofixation assays that monitor for endogenous m-protein.
    • These assays may be affected by elotuzumab interference. This could affect the determination and progression of disease in certain patients with IgG-kappa myeloma protein.

Elotuzumab: Drug Interaction Note: Drug Interaction Categories:

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

Monitoring parameters:

• Liver function tests (periodically);
• signs/symptoms of infusion reactions (monitor vital signs every 30 minutes during and for 2 hours after the end of the infusion in patients who experience an infusion reaction), infections, and second primary malignancies

How to administer Elotuzumab (Empliciti)?

• • • • Only for IV infusion. You should not give IV push or bolus.
      • Before administering dexamethasone, Acetaminophen, or an H-1 or H-2 blocker (see Dosing), you should premedicate for approximately 45 to 90 seconds.
      • Infuse in a setting that can monitor and manage infusion reactions.
      • Use an automated infusion pump to administer the infusion set.
      • Do not mix or infuse other medications. Within 24 hours of reconstitution, the infusion should be complete.
      • Watch out for infusion reactions
      • Infusion may be interrupted for grade 2 and higher reactions. If the reaction resolves or improves to =grade 1, infusion may resume (see Dosage Adjustment For Toxicity).
      • Patients who have an infusion reaction should have their vital signs checked every 30 minutes and for two hours thereafter.

  Dosage: Infusion rate: 10mg/kg

  • • • First infusion (Cycle 1, Dose 1)
        • For the first 30 minutes, infuse at 0.5mL/minute
        • Infusion reactions are not possible. The rate may be increased to 1 mL/minute over the next 30 minutes.
        • If it is tolerated, it can then increase the rate up to 2 mL/minute till infusion complete (maximum rate: 2,5 mL/minute).
      • Second infusion (Cycle 1, Dose 2):
        • Infusion reactions that did not occur during the previous infusion should be avoided.
        • If tolerated, you may increase the rate to 4mL/minute until infusion complete (maximum rate 4mL/minute).
      • Infusions following (Cycle 1, Doses 3, and 4, and all subsequent infusions thereafter):
        • Infuse at 5mL/minute until the infusion is complete if there were no infusion reactions. Maximum rate: 5mL/minute

  Dosage: 20 mg/kg

  • • Dose 1: First infusion
      • For the first 30 minutes, infuse at 3 mL/minute
      • However, the infusion rates at 10 mg/kg must be reduced to 3 mL/minute for the 20 mg/kg dose.
      • Infusion reactions that do not occur at 3mL/minute may be increased to 4mL/minute until the infusion is complete (maximum: 4mL/minute).
    • Second infusion (Dose 2)
      • Infuse at 5mL/minute until the infusion is complete if there were no infusion reactions. Maximum rate: 5mL/minute

Mechanism of action of Elotuzumab (Empliciti):

Elotuzumab, a monoclonal humanized IgG1 immunostimulatory monoclonal anti-signing lymphocytic activation molecule 7 (SLAMF7), is a directed against the signaling lymphocytic stimulation molecule family member 7. SLAMF7 is expressed in most myeloma cells and natural killer cells but not in normal tissues.

More than 95% bone marrow myeloma cell cells express SLAMF7. (Lonial 2015). Elotuzumab activates natural killer cell directly through the Fc receptors and the SLAMF7 pathway. It also targets SLAMF7 in myeloma cell lines and mediates antibody dependent cellular cytotoxicity through the CD16 pathway. Through the activation of more natural killer cells, this immunostimulatory activity increases anti-tumor activities. Eliminating half-life

• • With a geometric mean (CV%) between 78 and 82.4 days, 97% is expected to be eliminated from the maximum steady-state concentration.

International Brand Names of Elotuzumab:

• Empliciti

Elotuzumab Brand Names in Pakistan:

• No Brands are Available in Pakistan.