Empliciti (elotuzumab)

EMPLICITI® (elotuzumab) is the first monoclonal antibody approved to treat multiple myeloma. It is given intravenously (into the vein, IV) and taken in combination with the medicines Revlimid® (lenalidomide) and dexamethasone, in people who have received 1 to 3 prior treatments for their disease. It is also approved for use in combination with Pomalyst® and dexamethasone in patients with myeloma who have received at least 2 prior therapies including Revlimid and a proteasome inhibitor.

How Empliciti Works?

Empliciti is the first immunostimulatory monoclonal antibody approved by the FDA for the treatment of myeloma. Although antibodies are a naturally-occurring part of the immune system, the antibodies used to treat cancer are made in a laboratory and designed to target a specific protein on the surface of cancer cells. 

Empliciti is designed to target a protein called SLAMF7 (signaling lymphocytic activation molecule F7) that is found on the surface of most myeloma cells. SLAMF7 also appears on the surface of immune system cells called natural killer (NK) cells. These NK cells patrol for, and kill, tumor cells.  

Empliciti attaches to the SLAMF7 receptor on NK cells. It stimulates the NK cells to attach to and attack myeloma cells via the SLAMF7 surface receptors on myeloma cells. By attaching directly to myeloma cells, Empliciti “flags” them for destruction by the NK cells.  

Thus, Empliciti works via a two-pronged approach: 

• It provides a docking site for NK cells on myeloma cells.  
• It recruits NK cells to attach to that dock and directly attack the myeloma cells from the outside in.  

Because Empliciti stimulates these immune system cells to attack myeloma cells, it not only helps to cause myeloma cell death. It also stimulates an ongoing immune response against 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. 

The FDA approval of Empliciti in combination with Revlimid® (lenalidomide) and dexamethasone (Rd) was based on data from the phase III, randomized ELOQUENT-2 clinical trial for patients with relapsed and/or refractory myeloma. 

In the ELOQUENT-2 clinical trial, 646 patients were enrolled at 224 study sites across 21 countries, with 321 patients randomly assigned to the experimental group of Empliciti, Revlimid, and dexamethasone (ERd) and 325 patients assigned to the control group of Rd. All patients had received from 1 to 3 prior therapies and were not resistant to Revlimid. Nearly a third of the patients had high-risk multiple myeloma (HRMM) and more than a third were refractory to their last therapy. Patients were treated until their myeloma progressed or until they were unable to tolerate the therapy. 

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. 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. 

Data from the phase II ELOQUENT-3 clinical trial, presented at the European Hematology Association (EHA) meeting in June 2018, compared Empliciti, Pomalyst® (pomalidomide), and dexamethasone (EPd) to Pomalyst, and dexamethasone (Pd) for treatment of relapsed/refractory myeloma. Study participants included 117 patients who had at least two prior lines of therapy and whose myeloma progressed despite treatment that included Revlimid and a proteasome inhibitor (Velcade® [bortezomib], Ninlaro® [ixazomib], or Kyprolis® [carfilzomib]). Patients treated with EPd had a longer response or remission duration (10.3 months) than patients treated with Pd (4.7 months), and the treatment had an acceptable safety profile. 

The FDA approved EPd for relapsed or treatment-resistant myeloma in November 2018. Data from the phase II SWOG-1211 clinical trial, which compared Velcade, Revlimid, and dexamethasone (VRd) with and without Empliciti for newly diagnosed HRMM, were presented at the American Society of Clinical Oncology (ASCO) meeting in May 2020. The addition of Empliciti to VRd induction and maintenance did not improve patient outcomes for this patient population, but the PFS and OS seen in both arms of the study were better than the original statistical assumptions.  

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. 

What Are the Indications for the Use of Empliciti? 

In November 2015, the FDA approved Empliciti in combination with Revlimid and dexamethasone 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 (Pd) for the treatment of adult patients with myeloma who have received at least 2 prior therapies, including Revlimid and a proteasome inhibitor. 

How Empliciti Is 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, and subsequently can be given at 2 mg/minute. By the third cycle of treatment, at the doctor’s discretion, the rate of infusion may increase 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. 

ERd 

• Each dosing cycle of Empliciti, Revlimid, and dexamethasone (ERd) therapy is 28 days long.  
• 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). 
• After the first two cycles, patients receive Empliciti every other week (on Days 1 and 15), repeated every 28 days.  
• Revlimid is taken orally at a dose of 25 mg (on Days 1–21 of each cycle) and dexamethasone is given orally at a dose of 40 mg (on Days 1, 8, 15, and 22 of each cycle). 

EPd 

• For the first two cycles of Empliciti, Pomalyst, dexamethasone (EPd) therapy, Empliciti is given at a dose of 10 mg/kg every week. 
•  After that, it is given at a dose of 20 mg/kg every 4 weeks until disease progression or unacceptable toxicity.  
• Pomalyst is taken orally at a dose of 4 mg on Days 1–21. 

Empliciti Dose and Schedule

The following lists the dose and schedule for ERd, which is an abbreviation for Empliciti (elotuzumab), Revlimid (lenalidomide), and dexamethasone. 

*prescribing information 2015

For information about the dose and schedule for EPd, which is an abbreviation for Empliciti (elotuzumab), Pomalsyt, (pomalidomide), and dexamethasone, see EMPLICITI-Dosing-Guide.pdf (emplicitihcp.com)

Possible Side Effects of Empliciti 

Side effects (adverse events) were nearly equal in the experimental and control arms of clinical trials, demonstrating that Empliciti adds little or no toxicity over that of Rd or Pd. Of the common side effects that occurred in 30% or more of the patients who participated in these trials, adverse events affecting the blood cells were most prevalent. The most serious blood cell-related side effects were low white cell counts.  

Among side effects other than low blood cell counts, infections were most common, pneumonia in particular (a direct result of low white cell counts). Approximately 25% of the patients in both arms of the ELOQUENT-2 clinical trial had infections of Grade 3 or Grade 4, meaning that they were ill enough to be hospitalized, and that the most severe cases (Grade 4) were life-threatening.  

Fatigue and diarrhea were the next most common adverse events. Both occurred in 47% of patients, although fewer than 9% of the cases of fatigue and 5% of the cases of diarrhea were serious enough to prevent the patients from performing the activities of daily living. The next most common adverse events were fever (which occurred in 37% of patients), constipation (36%), cough (31%), and muscle spasms (30%).  

Infusion-related reaction (IRR)  

An 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 with Empliciti are likely to be cytokine-mediated and subside 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 2 out 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  

Patients may experience a lowered level of lymphocytes and neutrophils. White blood cells (WBC) help to fight infection. Too few white blood cells can lead to infections.  

Prevention and treatment of lymphocytopenia and neutropenia 

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.  

Prevention and treatment of anemia  

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.  

Prevention and treatment of thrombocytopenia  

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 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.  

Prevention and treatment of fatigue  

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

Diarrhea  

Diarrhea may occur while taking Empliciti. Diarrhea is defined as 3 or more loose stools per day, and severe diarrhea is defined as 7 or more loose stools per day requiring treatment with intravenous fluids or hospitalization. Dizziness, light-headedness, or fainting may occur due to dehydration caused by either excessive or persistent diarrhea.  

Prevention and treatment of diarrhea 

Precautions should be taken to prevent dehydration caused by either excessive or persistent diarrhea. You should maintain a proper level of hydration by drinking enough 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 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.  

Prevention and treatment of fever  

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 

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. 

Prevention and treatment of constipation 

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 

Infections as mild as a cold (an upper respiratory tract infection) or as severe as pneumonia can occur in people who receive Empliciti. Cough, runny nose, and sore throat are all common side effects experienced by patients taking Empliciti and may be signs of an upper respiratory tract infection. The signs and symptoms of pneumonia vary depending on what is causing the infection. Mild signs and symptoms are similar to those of a cold or flu, but they last longer. 

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 

Prevention and treatment of infections 

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 

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. 

Prevention and treatment of muscle spasms 

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. 

Prevention and treatment of decreased appetite 

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.