Empliciti (elotuzumab)

EMPLICITI® (known also by its generic drug name, elotuzumab, or “elo” for short) was first approved by the U.S. Food and Drug Administration (FDA) in 2015 for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who have received 1 to 3 prior therapies. The FDA approval was based primarily on data from the ELOQUENT-2 clinical
trial.

In 2018, the FDA expanded its approval of Empliciti to patients with RRMM who have received at least 2 prior therapies, including the immunomodulatory agent Revlimid® (lenalidomide) and a medication in the proteasome inhibitor drug class – Velcade® (bortezomib), Ninlaro® (ixazomib), or Kyprolis® (carfilzomib).

How Does Empliciti Work?

Antibodies are a natural part of the human immune system. These proteins are produced by plasma cells in response to any foreign substance that enters the body. 

Empliciti is in a drug class called monoclonal antibodies (mAb), made in a laboratory and designed to target a specific protein on the surface of cancer cells. Empliciti is the first medication in this drug class approved by the FDA for the treatment of myeloma.

Empliciti works in two ways:

1. Empliciti causes myeloma cell death. First, it finds and attaches to a protein called SLAMF7 (signaling lymphocytic activation molecule F7) on the surface of myeloma cells. Next, Empliciti “tags” the myeloma cells and creates a docking site for immune system cells called natural killer (NK) cells on the surface of the myeloma cells.
2. Empliciti also stimulates the human immune system to have an ongoing immune response against myeloma. Empliciti attaches to the SLAMF7 receptor on the surface of NK cells and helps the NK cells to target and destroy myeloma cells.

For more information about immune system cell types and functions, how they work together to protect us, and the impact of myeloma on the immune system, read the IMF’s publication,read the IMF publication, Understanding the Immune System in Myeloma. Learn more about Empliciti's mechanism of action with this Myeloma Made Simple video.

Clinical Trial Experience with Empliciti

A clinical trial is a medical research study with people who volunteer to test scientific approaches to a new treatment or a new combination therapy. Each clinical trial is designed to find better ways to prevent, detect, diagnose, or treat cancer and to answer scientific questions.

Rd vs. ERd 

The FDA approval of Empliciti in 2015 was based on data from the phase 3, randomized ELOQUENT-2 clinical trial. At 224 study sites across 21 countries, 646 patients were randomly assigned (randomized) as follows: 325 patients received treatment with Revlimid and dexamethasone, or Rd; and 321 patients received Empliciti and Rd, or ERd.

All patients had 1 to 3 prior therapies and were not resistant to Revlimid. Nearly a third of study patients had high-risk multiple myeloma (HRMM), a more aggressive form of the disease that is more likely to be resistant to treatment and to relapse more quickly. More than a third of enrolled patients were refractory to their last therapy. Patients were treated until they were until they were unable to tolerate their therapy or until their myeloma progressed.

The ELOQUENT-2 clinical trial demonstrated that the addition of Empliciti to Rd resulted in a 27% reduction in the risk of disease progression or death. Over time, the difference between the progression-free survival (PFS) of patients treated with ERd and those treated with Rd became greater. At median follow-up of 32.4 months, median PFS was 19.4 months with ERd versus 14.9 months with Rd. 

PFS is the length of time during and after the treatment that a patient lives with myeloma, but the disease does not get worse. In clinical trials, PFS is a way to measure how well the treatment works.The benefit for PFS was consistent even among elderly patients and those with high-risk multiple myeloma (HRMM), and the addition of Empliciti to Rd did not increase the incidence of side effects when compared to Rd alone.  

Earlier myeloma clinical trials compared Empliciti monotherapy to the ERd combination, demonstrating that the immunomodulatory agent (Revlimid) is a necessary part of the therapy. When used without Revlimid, Empliciti was only minimally effective against myeloma. Revlimid has its own effect on the NK cells, enabling them to kill myeloma cells more effectively. Revlimid also triggers cytokines that both activate NK cells and shut down another cytokine called interleukin-6 (IL-6), a growth factor for myeloma cells. 

Pd vs. EPd

The FDA expanded approval of Empliciti in 2018 was based on the phase 2 ELOQUENT-3 clinical trial. Data from this study was presented in June 2018 at the European Hematology Association (EHA) meeting. This study compared the combination of Empliciti with Pomalyst® (pomalidomide) and dexamethasone (ERd) to Pd without Empliciti for treatment of RRMM.

The study included 117 patients who had at least 2 prior lines of therapy and whose myeloma progressed despite treatment that included Revlimid and a proteasome inhibitor. Patients treated with EPd had a longer duration of response or remission, 10.3 months vs. 4.7 months with Pd. EPd showed an acceptable safety profile.

SWOG-1211 clinical trial

The phase 2 SWOG-1211 clinical trial studied the combination of Velcade, Revlimid and dexamethasone (VRd) vs. Empliciti and VRd (Elo-VRd) for newly diagnosed patients with HRMM. Historically, patients with HRMM have a poor long-term prognosis. SWOG-1211 was the first randomized study in newly diagnosed HRMM.

At a median follow-up of 6 years, the addition of Empliciti to VRd induction therapy and maintenance therapy did not improve PFS and overall survival (OS). However, the PFS and OS in patients with 1q21 and del17p chromosomal abnormalities may serve as valuable benchmarks for future HRMM clinical trials of combination therapies with proteasome inhibitors and immunomodulatory agents.

Find a Matching Clinical Trial   

For more information about clinical trials with Empliciti in various myeloma disease settings and in combination with other drugs, please visit clinicaltrials.gov or contact the IMF InfoLine. Be sure to also visit the IMF's Clinical Trials Matching Engine powered by SparkCures.

What Are the Indications for the Use of Empliciti? 

In November 2015, the FDA approved Empliciti in combination with Revlimid and dexamethasone (ERd) for the treatment of adult patients with myeloma who have received 1 to 3 prior therapies. 

In November 2018, the FDA approved Empliciti in combination with Pomalyst and dexamethasone (EPd) for the treatment of adult patients with myeloma who have received at least 2 prior therapies, including Revlimid and a proteasome inhibitor. 

Learn more about the drugs use in combination with Empliciti n the following IMF publications:

Understanding Dexamethasone in the Treatment of Myeloma
Understanding POMALYST® (pomalidomide)
Understanding REVLIMID® (lenalidomide)

How Is Empliciti Given?

Empliciti is given as an intravenous (IV) infusion. Dosing is determined by a patient’s weight. To ensure tolerance, Empliciti is infused very slowly at first at a rate of 0.5 milligrams (mg) per minute. For the second cycle, it can be given at a rate of 2 mg/minute. By the third cycle of treatment, at the doctor’s discretion, your doctor may increase the rate of infusion to 5 mg/minute.

Medication is given before the infusion to help prevent an infusion-related reaction (IRR). IRR is a type of hypersensitivity reaction that develops during or shortly after an intravenous (IV) infusion. IRRs are caused by cytokines and can occur with many IV cancer therapies. 

Patients are premedicated 45 to 90 minutes prior to receiving their IV infusion of Empliciti with 8 mg IV dexamethasone, 25 to 50 mg H1-blocker (oral or IV), H2 blocker, and 650 to 1000 mg oral acetaminophen. Patients can be premedicated with oral dexamethasone 3 to 24 hours before their IV infusion of Empliciti.

Each Cycle of therapy with Empliciti is 28 Days long, with a rest period of Days 23 through 28. Treatment should continue until disease progression or unacceptable toxicity.

ERd dose and schedule  

• For the first two cycles, patients receive their Empliciti at the dose of 10 mg for every kilogram (kg) of body weight once-weekly on Days 1, 8, 15, and 22 of each cycle. For the third cyle and onward, patients receive Empliciti every other week on Days 1 and 12 of each cycle.
• Revlimid is taken orally (by mouth) at a dose of 25 mg on Days 1 through 21 of each Cycle.
• Dexamethasone is given orally or as an IV infusion at a dose of 40 mg on Days 1, 8, 15, and 22 of each cycle.

EPd dose and schedule

• For the first two cycles of Empliciti, Pomalyst, dexamethasone (EPd) therapy, Empliciti is given at a dose of 10 mg/kg every week. For the third cycle and onward, patients receive Empliciti at a dose of 20 mg/kg once every 4 weeks.
• Pomalyst is taken orally at a dose of 4 mg on Days 1–21. 
• Dexamethasone is given as follows for the first two cycles:
  • Patients age 75 and younger receive 28 mg of dexamethasone
    orally on Days 1, 8, 15, and 22.
  •  Patients older than age 75 receive 8 mg.
• Dexamethasone is given as follows for the third Cycle and onward:
  • Patients age 75 and younger receive 28 mg on Day 1,
    and 40 mg on Days 8, 15, and 22.
  • Patients older than age 75 receive 8 mg on Day 1 and 28 mg
    on Days 8, 15, and 22.

For more detailed dosing and schedule information, visit Empliciti-Dosing-Guide.pdf or contact the IMF InfoLine.

Possible Side Effects of Empliciti 

In clinical trials with Empliciti, side effects (adverse events) were nearly equal in both the experimental and the control arms. This shows that Empliciti adds little or no toxicity to the treatment with Rd or Pd.

Infusion-related reaction

An infusion-related reaction (IRR) is a type of hypersensitivity reaction that develops during or shortly after an IV infusion. IRRs are caused by cytokines and can occur with many IV cancer therapies. Reactions are often flu-like, and include nasal congestion, fever, chills, cough, throat irritation, shortness of breath, low blood pressure, nausea, and rash.  

Monoclonal antibodies were used to treat cancers for more than a decade before they were first approved by the FDA to be used in myeloma. Empliciti, like other monoclonal antibodies, is well tolerated. However, like many other monoclonal antibodies, Empliciti may cause IRR. This can happen during the IV infusion or within 24 hours afterward. 

In the ELOQUENT-2 clinical trial, this occurred in 10% of the patients who received Empliciti, although 70% of those infusion reactions occurred only with the first dose. Infusion reactions from Empliciti are likely to lessen with each subsequent dose. The most common infusion reactions were fever, chills, and elevated blood pressure (hypertension). There were no infusion reactions that were serious enough to require hospitalization, and only 2out of 321 patients dropped out of the ELOQUENT-2 clinical trial because of an infusion reaction.

Prevention and treatment of infusion reactions 

Contact your doctor to get medical help right away if you have any of these symptoms after your infusion of Empliciti: 

• fever 
• chills 
• rash 
• trouble breathing 
• dizziness 
• lightheadedness 

Premedications are given with each dose of Empliciti to reduce the risk of infusion reactions. Reactions can also be managed by pausing the infusion and/or restarting the infusion at a slower rate.  

Lymphocytopenia and neutropenia  

Of the common side effects that occurred in 30% or more of the patients in Empliciti clinical trials, the most serious blood cell-related side effects were low counts of white blood cells (WBC). Blood cells called lymphocytes and neutrophils help fight infection. Too few of these blood cells can lead to infections.

Inform your doctor immediately if you experience fever, sore throat, or mouth sores. Fever is the symptom that usually indicates infection in a person who has low neutrophils. Fever is an important sign that immediate medical attention is needed.

The treatment for lymphocytopenia and neutropenia depends on cause and severity. Sometimes the bone marrow (where new blood cells are made) recovers by itself without treatment. The neutropenia accompanying viral infections (such as influenza) may be short-lived and resolve after the infection has cleared. Mild neutropenia generally has no symptoms and may not need treatment.

Anemia (low red blood cell count) 

Red blood cells contain hemoglobin, a protein that carries oxygen to the body’s tissues and organs. Anemia is usually defined as a decrease in hemoglobin <10 g/dL or as a decrease of ≥ 2 g/dL from the normal level for an individual. More than 13–14 g/dL is considered normal. Low levels of oxygen in the body may cause shortness of breath and feelings of exhaustion. Anemia is not an immediate effect of Empliciti, but one that may appear with duration of treatment.  

Your healthcare providers will determine which treatment regimen for anemia is best suited to your needs and safest for you. The following are options for treatment of anemia:  

• adjusting medications 
• blood transfusions 
• erythropoietic (red blood cell-making) agents 

Thrombocytopenia  

Thrombocytopenia is a low number of platelets in the blood. Platelets help blood to clot; fewer platelets can lead to easier bruising, bleeding, and slower healing. The “normal” level of platelets varies from laboratory to laboratory. For example, the “normal” level is 150,000 or more platelets per microliter of circulating blood. Bleeding problems could occur if the count is less than 50,000 platelets. Major bleeding is usually associated with a reduction to less than 10,000 platelets.  

You should inform your doctor if you experience excessive bruising or bleeding. Management may include platelet transfusions or a thrombocyte growth-stimulating agent, at the discretion of your doctor. Learn more about myelosuppression.

Fatigue  

Fatigue occurred in 47% of Empliciti clinical trial patients. However, fewer than 9% of patients had fatigue serious enough to interfere with the activities of daily living.

Management of fatigue may include treatment, as determined by your doctor. The effects of fatigue may be minimized by maintaining:  

• a moderate level of activity 
• a healthy diet and proper fluid intake 
• a consistent sleeping schedule with enough rest 
• regularly scheduled visits with your doctor or healthcare provider to discuss fatigue issues  
• a careful review of the side effects of all the other supplements and medications you are taking in addition to Empliciti. Make sure that they are not contributing to your fatigue

Fatigue is commonly associated with cancer and with cancer therapy. Caution is advised if you are operating machinery, including automobiles. For more information, read the IMF publication Understanding Fatigue.  

Diarrhea  

Diarrhea occurred in 47% of Empliciti clinical trial patients. However, fewer than 5% of patients had diarrhea serious enough to interfere with the activities of daily living.

Diarrhea is defined as 3 or more loose stools per day, and severe diarrheais defined as 7 or more loose stools per day requiring treatment with intravenous fluids or hospitalization.

Persistent diarrhea may cause dehydration and lead to:

• Dizziness.
• Lightheadedness.
• Fainting.

Precautions should be taken to prevent dehydration caused by either excessive or persistent diarrhea. You should maintain a proper level of hydration by drinking a sufficient amount of water. Seek medical advice if you experience dizziness, light-headedness, or fainting. Your doctor may
administer antidiarrheal medication or IV hydration, as needed. Learn more about Gastrointestinal Problems. 

Fever 

Fever occurred in 37% of clinical trial patients. Fever is defined as an oral temperature greater than 38°C or 100.4°F in a 24-hour period, or one temperature greater than 38.5°C or 101.3°F. When the white cell count is low, the body’s normal defenses against infections are down, and fever needs to be further evaluated immediately. In clinical trials with Empliciti, fevers were likely caused by a reaction to medication and/or from a bacterial or viral infection.  

You can minimize the effects of fever in the following ways:  

• Check your temperature twice a day if you feel warm.  
• Notify your doctor immediately if you have a fever greater than 100.4°F (38°C).  
• If your doctor’s office is closed and you are not able to reach your healthcare team, go to an emergency room (ER) or urgent care facility.  
• Take medications to control the fever as directed by your doctor.  
• To avoid dehydration, drink a lot of non-alcoholic and non-caffeinated liquids.  

Your doctor may also do the following:  

• Tell you to use over-the-counter (OTC) medications or prescribe medication to treat fever related to flu-like symptoms. Do not take any medication without first consulting a doctor familiar with your medical history. Do not take more than the recommended amount of any medication.  
• Prescribe antibiotics if you have a fever as a result of an infection. You may also be given a colony-stimulating factor (CSF) to stimulate the development and growth of your WBCs. 

Constipation 

Constipation was experienced by 36% of clinical trial patients. Prevention is the key to managing constipation, which is defined as having fewer than three bowel movements a week. Chronic constipation is defined as infrequent bowel movements or difficult passage of stools that persists for several weeks or longer. 

These strategies may help alleviate constipation: 

• Drink at least eight 8-ounce glasses of fluid daily.
• Add plenty of dietary fiber every morning, such as prune juice, apple juice, or bran.
• Get some exercise daily, even if it’s just walking. Moving your body increases peristalsis, the rhythmic contractions that move food through the digestive system.
• Report the problem to a member of your healthcare team, who may recommend a stool softener or laxative.

Learn more about Gastrointestinal Problems. 

Infections 

Approximately 25% of the patients in both arms of the ELOQUENT-2 clinical trial had infections of Grade 3 or Grade 4. The most severe Grade 4 cases were life-threatening. Symptoms of pneumonia varied depending on what caused the infection. Pneumonia may be a direct result of low white cell counts.

Approximately 31% of clinical trial patients developed a cough. Other mild symptoms of infection are similar to a cold or flu – runny nose and sore throat – and may be signs of an upper respiratory tract infection. 

Alert your doctor immediately if you have any signs or symptoms of an infection, including the following: 

• fever 
• flu-like symptoms (body aches, sweating, chills, fatigue). 
• cough (which may produce phlegm). 
• shortness of breath 
• chest pain when you breathe or cough 
• burning with urination. 
• a painful skin rash 
• nausea, vomiting, or diarrhea 

Your doctor will determine how your symptoms should be managed, and if you need to receive an antibiotic or other medications. If your doctor or another doctor covering the practice is not available to diagnose or rule out pneumonia, which can be a severe infection, you should go to an urgent care or emergency facility. 

Muscle spasms 

About 30% of clinical trial patients experienced muscle spasms. Muscle spasms occur when a skeletal muscle contracts forcefully and involuntarily and does not relax. Leg muscles, especially the thighs, hamstrings, and calves, are most likely to contract, but any skeletal muscle in the body can cramp. Dehydration, electrolyte imbalance, and physical deconditioning may all cause muscle spasms, but they may also be related to neuropathy caused by treatment or arising from the myeloma itself. 

If you have frequent, painful muscle spasms and cramps that interfere with your sleep or your ability to perform the activities of daily living, you should report the problem to your healthcare provider. You may need a referral to a neurologist to help determine the origin of the problem, and if it is neurologic, to treat the neuropathy. 

Some non-neurologic causes of muscle spasms can be prevented by drinking adequate amounts of non-alcoholic and non-caffeinated liquids and getting some light daily exercise. If any of your electrolytes (e.g., sodium, potassium, calcium, magnesium, chloride, phosphate, bicarbonate) are low, your doctor may need to oversee an increase or decrease in your fluid intake and/or prescribe oral or intravenous mineral supplements. 

Decreased appetite 

There are many causes for loss of appetite during treatment, including side effects of treatment such as diarrhea and constipation. Anxiety, depression, pain, and/or a lack of physical activity may contribute to the problem. Good communication with members of your healthcare team will help them understand how you’re feeling physically and mentally, and may help determine the source of your appetite loss. 

• Managing your gastrointestinal health and controlling diarrhea or constipation while taking Empliciti is an important step in maintaining your appetite. 
• If you are losing weight, your doctor or nurse may refer you to a nutritionist or suggest a nutritional supplement to provide more calories. 
• If appropriate, your doctor may also refer you to a mental health counselor to help you with depression and/or anxiety. 

Clinical Trials

Clinical Trial Fact Sheet ELOQUENT-1 trial

Active, Not Recruiting

Phase III Study of Lenalidomide and Dexamethasone With or Without Elotuzumab to Treat Newly Diagnosed, Previously Untreated Multiple Myeloma.

Clinical Trial Fact Sheet ELOQUENT-2 trial

Active, Not Recruiting

Phase III Randomized, Open-label Trial of Lenalidomide/Dexamethasone With or Without Elotuzumab in Relapsed or Refractory Multiple Myeloma

Elotuzumab Open Clinical Trials

ClinicalTrials.gov is a registry of federally and privately supported clinical trials conducted in the U.S. and around the world. ClinicalTrials.gov gives you information about a trial's purpose, who may participate, locations, and phone numbers for more details. This information should be used in conjunction with advice from healthcare professionals.

Empliciti Support Program

The BMS Access Support® program can help you with your prescribed Empliciti medication. This program may offer financial assistance to help eligible patients access Empliciti at low or no cost. Visit bmsaccesssupport.com/patient for more information.