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Elotuzumab

Pronunciation

(el oh TOOZ ue mab)

Index Terms

  • BMS-901608
  • Empliciti
  • HuLuc63
  • PDL-063

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous:

Empliciti: 300 mg (1 ea); 400 mg (1 ea) [contains mouse (murine) and/or hamster protein, polysorbate 80]

Brand Names: U.S.

  • Empliciti

Pharmacologic Category

  • Antineoplastic Agent, Anti-SLAMF7
  • Antineoplastic Agent, Monoclonal Antibody

Pharmacology

Elotuzumab is a humanized IgG1 immunostimulatory monoclonal antibody directed against signaling lymphocytic activation molecule family member 7 (SLAMF7, also called CS1 [cell surface glycoprotein CD2 subset 1). SLAMF7 is expressed on most myeloma and natural killer cells, but not on normal tissues; more than 95% of bone marrow myeloma cells express SLAMF7 (Lonial, 2015). Elotuzumab directly activates natural killer cells through both the SLAMF7 pathway and Fc receptors. It also targets SLAMF7 on myeloma cells and mediates antibody-dependent cellular cytotoxicity (ADCC) through the CD16 pathway (Lonial, 2015). This immunostimulatory activity, through the increased activation of natural killer cells, increases anti-tumor activity.

Half-Life Elimination

~97% of the maximum steady-state concentration is expected to be eliminated with a geometric mean (CV%) of 82.4 days.

Special Populations Note

Body weight: Clearance increases with increasing body weight.

Use: Labeled Indications

Multiple myeloma, relapsed/refractory: Treatment of multiple myeloma (in combination with lenalidomide and dexamethasone) in patients who have received 1 to 3 prior therapies

Contraindications

There are no contraindications listed in the manufacturer’s labeling.

Dosing: Adult

Note: Premedicate with dexamethasone, an H1-blocker (eg, diphenhydramine), an H2-blocker (eg, ranitidine), and acetaminophen ~45 to 90 minutes prior to infusion (see Premedications below). Refer to the lenalidomide and dexamethasone monographs for dosing information.

Multiple myeloma, relapsed/refractory: IV: Continue until disease progression or unacceptable toxicity (Lonial, 2015)

Cycles 1 and 2: 10 mg/kg once weekly 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)

Premedications:

Dexamethasone: Oral and IV: 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 prior to infusion. On days that elotuzumab is not administered but dexamethasone is due (eg, days 8 and 22 of cycle 3 and beyond), administer the standard dexamethasone dose (40 mg orally).

Antipyretic: Oral: Acetaminophen 650 to 1000 mg

H1-blocker: IV or Oral: Diphenhydramine 25 to 50 mg or equivalent

H2-blocker: Ranitidine: 50 mg IV or 150 mg orally or equivalent

Dosing: Geriatric

Refer to Adult dosing

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer’s labeling; however, based on pharmacokinetics, dosage adjustment is not likely necessary.

Dosing: Hepatic Impairment

Hepatic impairment prior to treatment:

Mild impairment: There are no dosage adjustments provided in the manufacturer’s labeling; however, based on pharmacokinetics, dosage adjustment is not likely necessary.

Moderate to severe impairment: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

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

Dosing: Adjustment for Toxicity

Refer to lenalidomide monograph for dosage modifications for toxicity. If dosing of one drug in the regimen is delayed, interrupted, or discontinued, treatment with the other medications may continue as scheduled. However, if dexamethasone is delayed or discontinued, administer elotuzumab based on clinical judgment (due to hypersensitivity risk).

Infusion reactions: Grade 2 or greater: Interrupt infusion and manage symptoms as clinically appropriate. When symptoms improve to ≤ grade 1, restart elotuzumab infusion at a rate of 0.5 mL/minute and gradually increase the rate by 0.5 mL/minute every 30 minutes as tolerated to the rate at which the infusion reaction occurred. May continue to escalate the rate if there is no recurrence of the infusion reaction (see Administration). 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, discontinue the elotuzumab infusion and do not restart on that day. Severe infusion reactions may require therapy discontinuation and emergency management.

Reconstitution

Reconstitute the 300 mg vial with 13 mL of SWFI, and the 400 mg vial with 17 mL of SWFI (to a concentration of 25 mg/mL) with an 18-gauge or lower (eg, 17, 16, or 15) needle. Slight back pressure may occur during reconstitution. Rotate the vial to dissolve the lyophilized powder (holding the vial upright). To dissolve any powder on the stopper or top of the vial, invert the vial several times; avoid vigorous agitation. Do not shake. The powder should dissolve in <10 minutes. After dissolution, allow the reconstituted vials to stand for 5 to 10 minutes (solution should be colorless to slightly yellow, clear to slightly opalescent). Discard if any particulate matter or discoloration is observed.

Each vial contains overfill to allow for withdrawal of 12 mL (300 mg vial) and 16 mL (400 mg vial), respectively. Withdraw appropriate dose from each vial (maximum of 12 mL from the 300 mg vial and 16 mL from the 400 mg vial). Further dilute with 230 mL of 0.9% sodium chloride or D5W in a polyvinyl chloride or polyolefin infusion bag; the volume of diluent may be adjusted in order to not exceed 5 mL/kg of body weight. Do not mix with other medications.

Administration

For IV infusion only. Do not administer IV push or as a bolus. Premedicate with dexamethasone, acetaminophen, and an H1- and H2-blocker (see Dosing) approximately 45 to 90 minutes prior to administration. Infuse in an environment equipped to monitor for and manage infusion reactions. Administer with an infusion set and a sterile, non-pyrogenic, low protein-binding filter (0.2 to 1.2 micrometer) using an automated infusion pump. Do not mix with or infuse with other medications. Infusion should be completed within 24 hours of reconstitution. Monitor for infusion reaction. Interrupt infusion for grade 2 or higher infusion reactions; if the reaction resolves or improves to ≤ grade 1, may resume 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 rate:

First infusion (Cycle 1, Dose 1): Infuse at 0.5 mL/minute for the first 30 minutes. If no infusion reactions occur, may increase the rate to 1 mL/minute for the next 30 minutes. If tolerated, may then increase the rate to 2 mL/minute until infusion completion (maximum rate: 2 mL/minute).

Second infusion (Cycle 1, Dose 2): If no infusion reactions occurred during the prior infusion, initiate at 1 mL/minute for the first 30 minutes. If tolerated, may then increase the rate to 2 mL/minute until infusion completion (maximum rate: 2 mL/minute).

Subsequent infusions (Cycle 1, Doses 3 and 4 and all subsequent infusions): If no infusion reactions occurred during the prior infusion, initiate and infuse at 2 mL/minute until completion. In patients who have received 4 cycles of elotuzumab, the infusion rate may be increased to a maximum of 5 mL/minute.

Compatibility

Compatible in NS, D5W

Storage

Store intact vials at 2°C to 8°C (36°F to 46°F). Protect from light (store in the original packaging until use); do not freeze or shake. Solutions diluted for infusion in NS or D5W may be stored at 2°C to 8°C (36°F to 46°F) for up to 24 hours (protected from light). A maximum of 8 hours of the 24 hour storage time may be at room temperature and room light. Infusion must be completed within 24 hours of lyophilized powder reconstitution.

Drug Interactions

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Belimumab: Monoclonal Antibodies may enhance the adverse/toxic effect of Belimumab. Avoid combination

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Avoid combination

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination

Test Interactions

Elotuzumab may be detected on both serum protein electrophoresis (SPEP) and immunofixation assays used for multiple myeloma endogenous M-protein monitoring, and may affect the determination of complete response and disease progression of some patients with IgG kappa myeloma protein. A small peak in the early gamma region on SPEP that is IgG kappa on serum immunofixation may be attributed to elotuzumab (especially when endogenous myeloma protein is IgA, IgM, IgD, or lambda light chain restricted).

Adverse Reactions

All incidences reported in combination with lenalidomide and dexamethasone.

>10%:

Cardiovascular: Decreased heart rate (66%; <60 bpm), increased heart rate (48%; ≥100 bpm), altered blood pressure (systolic ≥160 mmHg: 33%; systolic <90 mmHg: 29%; diastolic ≥100 mmHg: 17%)

Central nervous system: Fatigue (62%), peripheral neuropathy (27%; grades 3/4: 4%), headache (15%)

Endocrine & metabolic: Hyperglycemia (89%), hypocalcemia (78%), hypoalbuminemia (73%), decreased serum bicarbonate (63%), hyperkalemia (32%), weight loss (14%)

Gastrointestinal: Diarrhea (47%), constipation (36%), decreased appetite (21%), vomiting (15%)

Hematologic & oncologic: Lymphocytopenia (13% to 99%; grades 3/4: 9% to 77%), leukopenia (91%; grades 3/4: 32%), thrombocytopenia (84%; grades 3/4: 19%)

Hepatic: Increased serum alkaline phosphatase (39%; grades 3/4: 1%)

Immunologic: Immunogenicity (19%; neutralizing: 6%)

Infection: Infection (81%; grades 3/4: 28%), opportunistic infection (22%), herpes zoster (14%), fungal infection (10%)

Neuromuscular & skeletal: Limb pain (16%)

Ophthalmic: Cataract (12%)

Respiratory: Cough (34%), nasopharyngitis (25%), upper respiratory tract infection (23%), pneumonia (15% to 20%), oropharyngeal pain (10%)

Miscellaneous: Fever (7% to 37%), infusion related reaction (10%; grade 3: 1%)

1% to 10%:

Cardiovascular: Chest pain (≥5%), pulmonary embolism (3%)

Central nervous system: Hypoesthesia (≥5%), mood changes (≥5%)

Dermatologic: Night sweats (≥5%)

Hematologic & oncologic: Second primary malignant neoplasm (9%), malignant neoplasm of skin (4%), solid tumor (4%), anemia (3%), malignant neoplasm (hematologic: 2%)

Hepatic: Hepatotoxicity (3%)

Hypersensitivity: Hypersensitivity (≥5%)

Renal: Acute renal failure (3%)

Respiratory: Respiratory tract infection (3%)

Warnings/Precautions

Concerns related to adverse effects:

• Hepatotoxicity: Liver enzyme elevations (AST/ALT more than 3 times ULN, total bilirubin more than 2 times ULN, and alkaline phosphatase less than 2 times ULN) have occurred. Monitor liver function tests periodically; may require treatment interruption and/or discontinuation.

• Infection: Infections were reported in the majority of multiple myeloma patients treated in the clinical trial, including fatal infections. Monitor for opportunistic, fungal, herpes zoster, and other infections during therapy; treat promptly if infections occur.

• Infusion reactions: Infusion reactions (eg, fever, chills, hypertension) have been reported; all reactions were grade 3 or lower. Bradycardia and hypotension have also occurred during infusion. The majority of infusion reactions (~70%) occurred during the first dose. Premedicate with dexamethasone, H1- and H2-blockers, and acetaminophen prior to each dose. Administer in a facility with immediate access to resuscitative measures (eg, glucocorticoids, epinephrine, bronchodilators, and/or oxygen). May require treatment interruption, infusion rate modification, and/or discontinuation.

• Secondary malignancy: Invasive second primary malignancies have been reported. The rate of hematologic malignancies was the same between the elotuzumab/lenalidomide/dexamethasone group versus the lenalidomide/dexamethasone group. Solid tumors and skin cancer were reported more frequently in the elotuzumab arm versus the control group. Monitor for the development of secondary malignancies.

Disease-related concerns:

• Interference with determination of myeloma response: Elotuzumab (a human IgG kappa monoclonal antibody) may be detected on serum protein electrophoresis and immunofixation assays which monitor for endogenous M-protein. Interference with these assays by elotuzumab may affect the determination of complete response and disease progression in some patients with IgG kappa myeloma protein.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

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

Pregnancy Considerations

Animal reproduction studies have not been conducted. Elotuzumab is indicted for use in combination with lenalidomide. Due to its potential to cause fetal harm, lenalidomide is only available through a REMS program. Males and females of reproductive potential using this combination must be able to comply with pregnancy testing and contraception requirements for lenalidomide. Refer to the lenalidomide monograph for additional information.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience loss of strength and energy, diarrhea, constipation, burning or numbness feeling, rhinitis, pharyngitis, lack of appetite, painful extremities, vomiting, or weight loss. Have patient report immediately to prescriber signs of infection, signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), signs of high potassium (abnormal heartbeat, confusion, dizziness, passing out, weakness, shortness of breath, numbness or tingling feeling), severe headache, dizziness, passing out, tachycardia, bradycardia, mole changes, skin growth, vision changes, angina, mood changes, night sweats, bruising, or bleeding (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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