Issuu

Multiple Myeloma

Understanding

EMPLICITI (elotuzumab)

September 2026 Edition

HAVE QUESTIONS? WE CAN HELP The IMF team is here to support you and your loved ones with the most up-to-date information about myeloma Call the IMF at 1.818.487.7455 (and press 1) or visit the web page at mmsm.link/infoline to schedule a time to talk with us about your myeloma experience or if you wish to discuss the contents of this booklet.

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Contents You are not alone

Have questions? We can help

IMF publications

Understanding myeloma vocabulary

What you will learn from this booklet

Who can be treated with Empliciti

How Empliciti works

Clinical trial experience with Empliciti

How Empliciti is given

Possible side effects

Empliciti support program

In closing

You are not alone

The International Myeloma Foundation (IMF) has a mission: Accelerating the prevention and cure of myeloma and improving the quality of life for patients and families. The IMF gives information and support for people with multiple myeloma (also known as “myeloma”) and their care partners, friends, and family members. We do this on our website, myeloma.org, and through many programs and services like booklets, tip cards, classes, webinars, workshops, support groups, and much more.

Have questions? We can help

Myeloma is a cancer that many people have not heard of at the time of their diagnosis. The IMF can help you learn more about myeloma, understand what resources are available, and help you live well with this disease. The IMF can give you current information so you can work with your doctor to make the best decisions for your health. ¡ For information and support, call the IMF at 1.818.487.7455 (and press 1) or visit mmsm.link/infoline to schedule a time to talk with us. ¡ Want answers and don’t want to wait? Ask Myelo®, your AI assistant at myeloma.org. Myelo will help you find the right information and resources 24/7.

IMF publications

The IMF’s Patient Handbook explains what myeloma is, how doctors test for it, and how it affects the body. The Patient Handbook also introduces you to the many ways to treat myeloma and to manage its symptoms. The Patient Handbook also directs you to many helpful resources. The IMF’s Understanding-series booklets offer more information about different myeloma-specific topics, such as symptoms, treatments, and possible side effects. All IMF publications are free and can be read online, downloaded, or mailed to you. If you would like to read IMF publications digitally, just click on the light blue links in this booklet or go to publications.myeloma.org.

Understanding myeloma vocabulary

Myeloma is a complicated disease, but the language that describes it doesn’t have to be hard to understand. Getting comfortable with the language of myeloma will help you learn more about this disease and have better communication with your healthcare team. Words in bold+blue in this booklet are explained in the IMF’s companion publication, Understanding Myeloma Vocabulary, which is located at glossary.myeloma.org. 4

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What you will learn from this booklet

This booklet discusses Empliciti® (also known as elotuzumab, its generic drug name, or “elo” for short). You will learn who can be treated with Empliciti, how Empliciti works, its dose and schedule, and clinical trial experience with Empliciti. You will also learn about support programs for patients who are prescribed Empliciti, and the precautions and possible side effects for you to discuss with your doctor.

Who can be treated with Empliciti

Empliciti 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, which is discussed later in this booklet. Relapsed myeloma has come back after a period of improvement. Patients with relapsed disease have been treated, then developed signs and symptoms of myeloma at least 60 days after treatment ended. Refractory myeloma is disease that is no longer responsive to standard treatments. Patients whose myeloma progressed either during treatment or within 60 days following treatment are considered to have refractory disease. 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 Empliciti works

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. E mpliciti 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. E mpliciti also stimulates the human immune system to have an ongoing immune response against myeloma. Empliciti attaches to myeloma.org

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, Understanding the Immune System in Myeloma.

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 a medical condition, or to answer scientific questions. A clinical trial is launched only after laboratory studies have shown the potential of a treatment or procedure to be more effective and/or less harmful than previous methods. For patients with myeloma, clinical trials can be part of normal care that may provide earlier access to new drugs and therapies that are not yet available outside of a study.

Rd vs. ERd

The FDA approval of Empliciti in 2015 was based on data from the phase III, 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 + dexamethasone [Rd] and 321 patients received Empliciti + Rd [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 unable to tolerate their therapy or until their myeloma progressed. The ELOQUENT-2 study 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 progression-free survival (PFS) of patients treated with ERd and those treated with Rd increased. At median follow-up of 32.4 months, median PFS was 19.4 months with ERd vs. 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 in the ELOQUENT-2 study was consistent, including among elderly patients and patients with HRMM. In addition, the ERd combination did not increase the rate of side effects when compared to Rd alone. 6

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Earlier myeloma studies compared Empliciti monotherapy (treatment that uses only one drug) to the ERd combination, showing that Revlimid is a necessary part of the therapy. When used without Revlimid, Empliciti was not very 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 II 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) + 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.

VRd vs. Elo-VRd

The SWOG-1211 clinical trial studied the combination of Velcade + Revlimid + dexamethasone [VRd] vs. Empliciti + VRd [Elo-VRd] for newly diagnosed patients with HRMM. Historically, patients with HRMM have a poor longterm 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 + immunomodulatory agents.

Finding a clinical trial to match your needs

Myeloma clinical research is very exciting, with many studies enrolling patients. To help you with personalized support for identifying clinical trial options across the U.S., the IMF has partnered with SparkCures. Visit myeloma.org/sparkcures or contact the IMF InfoLine for more information. If you are interested in exploring your potential benefits and risks of clinical trial participation, speak with your myeloma doctor. To learn more about clinical trials in general, read the IMF’s publication Understanding Clinical Trials in Myeloma. myeloma.org

How Empliciti is given

Empliciti is given as an intravenous (IV) infusion into a vein. Dosing is determined by a patient’s weight. During the first Cycle of treatment, Empliciti is given 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. For the third Cycle and beyond, your doctor may increase the rate of infusion to 5 mg/minute. Medication is given before the infusion to help prevent an infusionrelated reaction (IRR). Patients are premedicated 45 to 90 minutes prior to receiving their IV infusion of Empliciti. These medications include 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 Empliciti at the dose of 10 mg for every kilogram (10 mg/kg) of body weight once-weekly on Days 1, 8, 15, and 22 of each Cycle. For the third Cycle and onward, patients receive Empliciti every other week on Days 1 and 15 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, Empliciti is given weekly at a dose of 10 mg/kg. 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 through 21 of each Cycle. ¡ 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.

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For more detailed dosing and schedule information, visit Empliciti-DosingGuide.pdf or contact the IMF InfoLine. To learn more about the drugs used in combination with Empliciti, read the following IMF publications: ¡ Understanding Dexamethasone in the Treatment of Myeloma ¡ Understanding POMALYST® (pomalidomide) ¡ Understanding REVLIMID® (lenalidomide)

Possible side effects

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 (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. 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 2 out of 321 patients dropped out of the ELOQUENT-2 clinical trial because of an infusion reaction. Contact your doctor to get medical help right away if you have any of these symptoms after your infusion of Empliciti: ¡ Fever. ¡ Chills. ¡ Light-headedness. ¡ Rash. ¡ Dizziness. ¡ Trouble breathing. 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 myeloma.org

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 exhaustion. Anemia is not an immediate effect of Empliciti, but it may develop over time. 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, at Mayo Clinic 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.

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. 10

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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. ¡ Ask your doctor if any of the other medications and supplements you are taking may be 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’s publication Understanding Fatigue in Myeloma.

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 diarrhea is 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.

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). myeloma.org

¡ 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.

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. 12

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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. Non-neurologic causes of muscle spasms can be prevented by drinking adequate amounts of non-alcoholic and non-caffeinated liquids. Daily light exercise may help as well. If any of your electrolytes are low, your doctor may direct you to increase or decrease your fluid intake, or prescribe specific 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 myeloma.org

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.

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.

In closing

This booklet is not meant to replace the advice of your doctors and nurses who are best able to answer questions about your specific healthcare management plan. The IMF provides educational information that will guide you in your conversations with your healthcare team. To help ensure a good quality of life through effective treatment, you must have an active role in your own medical care. Please visit myeloma.org and join the IMF Myeloma Knowledge Platform at myprofile.myeloma.org. Click on the links included in this booklet for quick access to a variety of resources. Sign up at subscribe.myeloma.org for our quarterly journal Myeloma Today and weekly e-newsletter Myeloma Minute, as well as alerts about IMF news, events, and actions.

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Founded in 1990, the International Myeloma Foundation (IMF) is the world’s leading organization dedicated to multiple myeloma. The IMF is steadfast in its mission: Accelerating the prevention and cure of myeloma and improving the quality of life for patients and families. The IMF serves people impacted by myeloma at every stage of the disease by combining world-class research, trusted education, global advocacy, and direct support. A cornerstone of this work is the International Myeloma Working Group® (IMWG) – a network of more than 300 internationally renowned researchers and clinicians who establish the guidelines that shape how myeloma is diagnosed, treated, and managed across the globe. Through its global network of support groups, educational programs, its 24/7 generative-AI myeloma assistant Myelo®, and its advocacy for greater healthcare access, the IMF helps people living with myeloma and their care partners navigate diagnosis, treatment, and survivorship. At the same time, the IMF ensures scientific advances translate into better care and outcomes. Learn more at

myeloma.org

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