Empliciti

Pregnancy

Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications; estimated background risk of major birth defects and miscarriage for the indicated population is unknown

Animal reproduction studies have not been conducted with elotuzumab

Lenalidomide (part of the combination regimen) can cause embryo-fetal harm and is contraindicated for use in pregnancy

Contraception

• Women of childbearing age and men with partners of childbearing potential must use effect contraception beginning 4 weeks prior to initiating treatment with lenalidomide, during treatment, treatment interruptions, and for 28 days following cessation of treatment with lenalidomide
• Females of reproductive potential must commit either to abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control simultaneously (1 highly effective form of contraception – tubal ligation, IUD, hormonal (birth control pills, injections, hormonal patches, vaginal rings or implants), or partner’s vasectomy and 1 additional effective contraceptive method – male latex or synthetic condom, diaphragm, or cervical cap
• Lenalidomide is present in the semen of males; therefore, males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking lenalidomide, during dose interruptions, and for up to 28 days after discontinuing lenalidomide, even if they have undergone a successful vasectomy
• Males taking lenalidomide must not donate sperm

Lactation

Unknown if distributed in human breast milk

Breast feeding is not recommended

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

EMPLICITI is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received one to three prior therapies.

Empliciti is a prescription medication used, with two other medications, to treat multiple myeloma, a type of blood cancer. It is given to patients who have received one to three prior therapies. 

It belongs to a group of drugs called monoclonal antibodies. These drugs work by helping certain cells in the immune system attack cancer cells.

This medication is available as a solution that is injected into the vein (IV) by a healthcare professional. It is typically given once a week for the first two cycles and every two weeks, thereafter. 

Common side effects include pneumonia, fever, and respiratory tract infection.

• Bristol-Myers Squibb Company

Serious side effects have been reported with Empliciti. See the "Empliciti Precautions" section.

Common side effects of Empliciti include the following:

• fatigue
• diarrhea
• fever
• constipation
• cough
• numbness, weakness, tingling, or burning pain in your arms or legs
• sore throat or runny nose
• upper respiratory tract infection
• decreased appetite
• pneumonia

This is not a complete list of Empliciti side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Elotuzumab is a monoclonal antibody that blocks a certain protein in the body that can affect tumor cell growth. Monoclonal antibodies are made to target and destroy only certain cells in the body. This may help to protect healthy cells from damage.

Elotuzumab is used in combination chemotherapy to treat multiple myeloma (bone marrow cancer). Elotuzumab is given together with lenalidomide and a steroid medicine called dexamethasone.

Lenalidomide (Revlimid) is available only under a special program. You must be registered in the program and understand the risks and benefits of taking this medicine.

Elotuzumab may also be used for purposes not listed in this medication guide.

Antineoplastic agent; recombinant humanized monoclonal antibody that is an antagonist of signaling lymphocytic activation molecule (SLAM) family member 7 (SLAMF7);1 6 also referred as an anti-CS1 (anti-CD2 subset 1) monoclonal antibody.2 10 11 12 16

Multiple Myeloma

Used in combination with lenalidomide and dexamethasone for the treatment of multiple myeloma in patients who have received 1–3 prior therapies1 2 14 (designated an orphan drug by FDA for treatment of this cancer3 ).

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as an infusion into a vein over a period of time.
• Other drugs may be given to help with infusion side effects.

What do I do if I miss a dose?

• Call your doctor to find out what to do.
• If you miss a dose of the steroid drug (dexamethasone) or if it is stopped, talk with your doctor.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take Empliciti or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Empliciti. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Infusion Reactions

Empliciti can cause infusion reactions. Infusion reactions were reported in approximately 10% of patients treated with Empliciti with lenalidomide and dexamethasone in the randomized trial in multiple myeloma. All reports of infusion reaction were Grade 3 or lower. Grade 3 infusion reactions occurred in 1% of patients. The most common symptoms of an infusion reaction included fever, chills, and hypertension. Bradycardia and hypotension also developed during infusions.

In the trial, 5% of patients required interruption of the administration of Empliciti for a median of 25 minutes due to infusion reactions, and 1% of patients discontinued due to infusion reactions. Of the patients who experienced an infusion reaction, 70% (23/33) had them during the first dose.

Administer premedication consisting of dexamethasone, antihistamines (H1 and H2 blockers) and acetaminophen prior to Empliciti infusion [see Dosage and Administration (2.2)].

Interrupt Empliciti infusion for Grade 2 or higher infusion reactions and institute appropriate medical management [see Dosage and Administration (2.3)].

Infections

In a clinical trial of patients with multiple myeloma (N=635), infections were reported in 81.4% of patients in the Empliciti combined with lenalidomide and dexamethasone (E-Ld) arm and 74.4% in lenalidomide and dexamethasone (Ld). Grade 3 to 4 infections were noted in 28% and 24.3% of E-Ld- and Ld-treated patients, respectively. Discontinuations due to infections occurred in 3.5% of E-Ld-treated and 4.1% of Ld-treated patients. Fatal infections were reported in 2.5% and 2.2% of E-Ld- and Ld-treated patients.

Opportunistic infections were reported in 22% of patients in the E-Ld arm and 12.9% of patients in the Ld arm. Fungal infections occurred in 9.7% of patients in the E-Ld arm and 5.4% of patients in the Ld arm. Herpes zoster was reported in 13.5% of patients treated with E-Ld and 6.9% of patients treated with Ld. Monitor patients for development of infections and treat promptly.

Second Primary Malignancies

In a clinical trial of patients with multiple myeloma (N=635), invasive second primary malignancies (SPM) have been observed in 9.1% of patients treated with E-Ld and 5.7% of patients treated with Ld. The rate of hematologic malignancies were the same between E-Ld and Ld treatment arms (1.6%). Solid tumors were reported in 3.5% and 2.2% of E-Ld- and Ld-treated patients, respectively. Skin cancer was reported in 4.4% and 2.8% of patients treated with E-Ld and Ld, respectively. Monitor patients for the development of second primary malignancies.

Hepatotoxicity

Elevations in liver enzymes (aspartate transaminase/alanine transaminase [AST/ALT] greater than 3 times the upper limit, total bilirubin greater than 2 times the upper limit, and alkaline phosphatase less than 2 times the upper limit) consistent with hepatotoxicity were reported in 2.5% and 0.6% of E-Ld- and Ld-treated patients in a clinical trial of patients with multiple myeloma (N=635). Two patients experiencing hepatotoxicity were not able to continue treatment; however, 6 out of 8 patients had resolution and were able to continue treatment. Monitor liver enzymes periodically. Stop Empliciti upon Grade 3 or higher elevation of liver enzymes. After return to baseline values, continuation of treatment may be considered.

Interference with Determination of Complete Response

Empliciti is a humanized IgG kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPEP) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein [see Drug Interactions (7.2)]. This interference can impact the determination of complete response and possibly relapse from complete response in patients with IgG kappa myeloma protein.

The following adverse reactions are described in detail in other sections of the label:

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety data described in this section are based on a randomized, open-label clinical trial in patients with previously treated multiple myeloma. In this study, Empliciti 10 mg/kg was administered with lenalidomide and dexamethasone [see Clinical Studies (14)]. For adverse reaction evaluation, Empliciti combined with lenalidomide and dexamethasone was compared with lenalidomide and dexamethasone alone.

The mean age of the population was 66 years and 57% of patients were 65 years of age or older. Sixty percent (60%) of the population were male, 84% were white, 10% were Asian, and 4% were black. The Eastern Cooperative Oncology Group (ECOG) performance status was 0 in 47%, 1 in 44%, and 2 in 9% of patients.

These data reflect exposure of 318 patients to Empliciti and 317 to control with a median number of cycles of 19 for Empliciti and 14 for control.

Serious adverse reactions were reported in 65.4% of patients treated on the Empliciti arm and 56.5% for patients treated on the control arm. The most frequent serious adverse reactions in the Empliciti arm compared to the control arm were: pneumonia (15.4% vs. 11%), pyrexia (6.9% vs. 4.7%), respiratory tract infection (3.1% vs. 1.3%), anemia (2.8% vs. 1.9%), pulmonary embolism (3.1% vs. 2.5%), and acute renal failure (2.5% vs. 1.9%).

The proportion of patients who discontinued any component of the treatment regimen due to adverse reactions as listed below was similar for both treatment arms; 6.0% for patients treated on the Empliciti arm and 6.3% for patients treated on the control.

Adverse reactions occurring at a frequency of 10% or higher in the Empliciti arm and 5% or higher than the lenalidomide and dexamethasone arm for the randomized trial in multiple myeloma are presented in Table 4.

Other clinically important adverse reactions reported in patients treated with Empliciti that did not meet the criteria for inclusion in Table 4 but occurred at a frequency of 5% or greater in the Empliciti group and at a frequency at least twice the control rate for the randomized trial in multiple myeloma are listed below:

General disorders and administration site conditions: chest pain

Immune system disorders: hypersensitivity

Nervous system disorders: hypoesthesia

Psychiatric disorders: mood altered

Skin and subcutaneous tissue disorders: night sweats

Laboratory abnormalities worsening from baseline and occurring at a frequency of 10% or higher in the Empliciti group and 5% or higher than the lenalidomide and dexamethasone group (criteria met for all Grades or Grade 3/4) for the randomized trial in multiple myeloma are presented in Table 5.

Vital sign abnormalities were assessed by treatment arm for the randomized trial in multiple myeloma and are presented in Table 6. Percentages are based on patients who had at least one on-treatment vital sign abnormality any time during the course of therapy.

Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity to Empliciti. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to Empliciti in the studies described below with the incidences of antibodies in other studies or to other products may be misleading.

Of 390 patients across four clinical studies who were treated with Empliciti and evaluable for the presence of anti-product antibodies, 72 patients (18.5%) tested positive for treatment-emergent anti-product antibodies by an electrochemiluminescent (ECL) assay. In 63 (88%) of these 72 patients, anti-product antibodies occurred within the first 2 months of the initiation of Empliciti treatment. Anti-product antibodies resolved by 2 to 4 months in 49 (78%) of these 63 patients. Neutralizing antibodies were detected in 19 of 299 patients in the randomized trial in multiple myeloma.

Empliciti (elotuzumab) is white to off-white lyophilized powder available as follows:

Store Empliciti under refrigeration at 2°C to 8°C (36°F-46°F). Protect Empliciti from light by storing in the original package until time of use. Do not freeze or shake.

Get emergency medical help if you have signs of an allergic reaction to Empliciti: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Some side effects may occur during the injection. Tell your caregiver right away if you feel dizzy, itchy, chilled, feverish, light-headed, or short of breath.

Call your doctor at once if you have:

• fever, chills, flu-like symptoms;

• pain or burning when you urinate;

• severe skin rash;

• liver problems - loss of appetite, upper stomach pain, tiredness, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or

• signs of pneumonia - cough with yellow or green mucus, stabbing chest pain, wheezing, feeling short of breath.

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

Common Empliciti side effects may include:

• fever, cough, tiredness;

• numbness, tingling, or burning pain in your arms or legs;

• loss of appetite;

• diarrhea, constipation; or

• cold symptoms such as runny nose or sore throat.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Applies to elotuzumab: intravenous powder for injection

Dermatologic

Common (1% to 10%): Night sweats[Ref]

Gastrointestinal

Very common (10% or more): Diarrhea (47%), constipation (36%), vomiting (15%), oropharyngeal pain (10%)[Ref]

Hematologic

Very common (10% or more): Lymphopenia (13%)
Frequency not reported: Leukopenia, thrombocytopenia, deep vein thrombosis[Ref]

Hepatic

Frequency not reported: Hypoalbuminemia, elevated alkaline phosphatase[Ref]

Hypersensitivity

Common (1% to 10%): Hypersensitivity
Uncommon (0.1% to 1%): Anaphylactic reaction[Ref]

Metabolic

Very common (10% or more): Decreased appetite (21%), weight loss (14%)
Frequency not reported: Hyperglycemia, hypocalcemia, low bicarbonate, hyperkalemia[Ref]

Musculoskeletal

Very common (10% or more): Pain in extremities (16%)
Common (1% to 10%): Chest pain[Ref]

Nervous system

Very common (10% or more): Peripheral neuropathy (27%), headache (15%)
Common (1% to 10%): Hypoesthesia[Ref]

Ocular

Very common (10% or more): Cataracts (12%)[Ref]

Oncologic

Common (1% to 10%): Invasive second primary malignancies (SPM)[Ref]

Other

Very common (10% or more): Fatigue (62%), pyrexia (37%)[Ref]

Psychiatric

Common (1% to 10%): Altered mood[Ref]

Renal

Common (1% to 10%): Acute renal failure[Ref]

Respiratory

Very common (10% or more): Cough (34%), nasopharyngitis (25%), upper respiratory tract infection (23%), pneumonia (20%)
Common (1% to 10%): Respiratory tract infection, pulmonary embolism[Ref]

Immunologic

Very common (10% or more): Herpes zoster[Ref]

Local

Common (1% to 10%): Infusion related reaction[Ref]

Some side effects of Empliciti may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.