Multiple Myeloma | Cancer of the Bone Marrow
Understanding
EMPLICITI
®
(elotuzumab)
October 2023 Edition A publication of the International Myeloma Foundation
Founded in 1990, the International Myeloma Foundation (IMF) is the first and largest organization focusing specifically on myeloma. The IMF’s reach extends to more than 525,000 members in 140 countries. The IMF is dedicated to improving the quality of life of myeloma patients while working toward prevention and a cure through our four founding principles: Research, Education, Support, and Advocacy.
RESEARCH The IMF is dedicated to finding a cure for myeloma, and we have a
range of initiatives to make this happen. The International Myeloma Working Group, which emerged from the IMF’s Scientific Advisory Board established in 1995, is the most prestigious organization with nearly 300 myeloma researchers conducting collaborative research to improve outcomes for patients while providing critically appraised consensus guidelines that are followed around the world. Our Black Swan Research Initiative® is bridging the gap from long-term remission to cure. Our annual Brian D. Novis Research Grant Program is supporting the most promising projects by junior and senior investigators. Our Nurse Leadership Board, comprised of nurses from leading myeloma treatment centers, develops recommendations for the nursing care of myeloma patients.
EDUCATION The IMF’s webinars, seminars, and workshops provide up-to-date
information presented by leading myeloma scientists and clinicians directly to patients and their families. We have a library of more than 100 publications for patients, care partners, and healthcare professionals. IMF publications are always free-of-charge, and available in English and select other languages.
SUPPORT The IMF InfoLine responds to your myeloma-related questions and
concerns via phone and email, providing the most accurate information in a caring and compassionate manner. We also sustain a network of myeloma support groups, training hundreds of dedicated patients, care partners, and nurses who volunteer to lead these groups in their communities.
ADVOCACY We empower thousands of individuals who make a positive impact each year on issues critical to the myeloma community. In the U.S., we lead coalitions to represent the interests of the myeloma community at both federal and state levels. Outside the U.S., the IMF’s Global Myeloma Action Network works to help patients gain access to treatment.
Learn more about the ways the IMF is helping to improve the quality of life of myeloma patients while working toward prevention and a cure. Call us at 1.818.487.7455 or 1.800.452.CURE, or visit myeloma.org.
Contents
You are not alone
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What you will learn from this booklet
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How Empliciti works
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Clinical trial experience with Empliciti
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The indication for use of Empliciti
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How Empliciti is given
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Possible side effects
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In closing
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Terms and definitions
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You are not alone
The International Myeloma Foundation is here to help you. The IMF is committed to providing information and support for patients with multiple myeloma (which we refer to simply as “myeloma”) and their care partners, friends, and family. We achieve this through a broad range of resources available on our website myeloma.org, the IMF InfoLine, seminars, webinars, workshops, and other programs and services.
What you will learn from this booklet
Myeloma is a cancer that is not known to most patients at the time of diagnosis. To play an active role in your own medical care and to make good decisions about your care with your Figure 1. Myeloma cells doctor, it is important and helpful to learn in the bone marrow about this disease, as well as its treatment options and supportive care measures. The information in this booklet can guide you in your discussions with your doctor. It is not intended to be a substitute for medical advice. Your doctor is best able to answer questions about your specific healthcare management plan. The IMF’s Understanding-series publications address treatments and supportive care measures for myeloma. This booklet discusses Empliciti® (known also by its generic drug name, elotuzumab, or “elo” for short), a treatment agent that was approved for use in myeloma by the U.S. Food and Drug Administration (FDA) in 2015. Empliciti enlists the immune system cells to attack myeloma. Before reading this booklet, it may be helpful to read another IMF publication, Understanding the Immune System in Myeloma, which will provide you with some background information on the types and functions of immune system cells, how they work together to protect us, and the impact of myeloma on the immune system. Words in bold+blue type are explained in the “Terms and definitions” section at the end of this booklet. The IMF’s publication Understanding Myeloma Vocabulary, a more complete myeloma-related compilation, is located online at glossary.myeloma.org. If you are reading this booklet in electronic format, the light blue links will take you to the corresponding resources. All IMF publications are free-of-charge and can be downloaded or requested in printed form at publications.myeloma.org. 4
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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 lympho cytic 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, which patrol for, and kill, tumor cells. Empliciti attaches to the SLAMF7 receptor on NK cells and 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. Empliciti thus works via a two-pronged approach: ¡ I t provides a docking site for NK cells on myeloma cells. ¡ I t 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. Figure 2. Using Empliciti to attack myeloma with NK (natural killer) cells
NK cell
myeloma cell CD16
SLAMF7
ACTIVATION
SLAMF7 Empliciti
myeloma.org
Empliciti
© 2015 Slaybaugh Studios
SLAMF7
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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) + 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 + 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 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 Figure 3. Blood cells that play a role in the immune system
Monocyte
NK cell Macrophage
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Lymphocyte
B lymphocyte
T lymphocyte
Plasma cell Dendritic cell
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© 2015 Slaybaugh Studios
Hematopoietic stem cell
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) + dexamethasone (EPd) to Pomalyst + dexameth asone (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 + 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.
The indication for use of Empliciti In November 2015, the FDA approved Empliciti in combination with Revlimid + 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 + 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). myeloma.org
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Each dosing cycle of Empliciti + Revlimid + 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). For the first two cycles of Empliciti + Pomalyst + dexamethasone (EPd) therapy, Empliciti is given at a dose of 10 mg/kg every week. Thereafter, 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.
Possible side effects
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, 8
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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. ¡R ash. ¡ T rouble breathing. ¡ Dizziness. ¡ Light-headedness. 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 myeloma.org
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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: ¡A djusting medications. ¡B lood transfusions. ¡ E rythropoietic (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. 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.
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. 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. ¡R egularly 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. 10
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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 a sufficient amount of water and seek medical advice if you experience dizziness, light-headedness, or fainting. Your doctor may administer antidiarrheal medication or IV hydration, as needed.
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: ¡C heck your temperature twice a day if you feel warm. ¡N otify your doctor immediately if you have a fever greater than 100.4°F (38°C). ¡ I f 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. ¡ T ake medications to control the fever as directed by your doctor. ¡ T o 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. myeloma.org
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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: ¡D rink at least eight 8-ounce glasses of fluid daily. ¡A dd plenty of dietary fiber every morning, such as prune juice, apple juice, or bran. ¡G et some exercise daily, even if it’s just walking. Moving your body increases peristalsis, the rhythmic contractions that move food through the digestive system. ¡R eport the problem to a member of your healthcare team, who may recommend a stool softener or laxative.
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: ¡ F ever. ¡ F lu-like symptoms (body aches, sweating, chills, fatigue). ¡C ough (which may produce phlegm). ¡ S hortness of breath. ¡C hest pain when you breathe or cough. ¡B urning with urination. ¡A painful skin rash. ¡N ausea, 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 12
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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
¡M anaging your gastrointestinal health and controlling diarrhea or constipation while taking Empliciti is an important step in maintaining your appetite. ¡ I f you are losing weight, your doctor or nurse may refer you to a nutritionist or suggest a nutritional supplement to provide more calories. ¡ I f appropriate, your doctor may also refer you to a mental health counselor to help you with depression and/or anxiety. myeloma.org
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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 intends only to provide you with information that will guide you in discussions with your healthcare team. To help ensure effective treatment with good quality of life, you must play an active role in your own medical care. We encourage you to visit myeloma.org for more information about myeloma and to contact the IMF InfoLine with your myeloma-related questions and concerns. The IMF InfoLine consistently provides the most up-to-date and accurate information about myeloma in a caring and compassionate manner. Contact the IMF InfoLine at 1.818.487.7455 or InfoLine@myeloma.org.
Terms and definitions
The following selected terms are used in this booklet, while a more complete compendium of myeloma-related terms can be found in the IMF’s publication Understanding Myeloma Vocabulary located online at glossary.myeloma.org. Administration-related reaction (ARR): Reaction to treatment administered as an intravenous (IV) infusion or a subcutaneous (SQ) injection. See “Infusion-related reaction (IRR)” and “Cytokine.” Adverse event (AE): See “Side effect.” Antibody: A protein produced by plasma cells in response to an antigen that enters the body. See “Immunoglobulin (Ig).” Antigen: Any foreign substance that causes the immune system to produce natural antibodies. Examples of antigens include bacteria, viruses, parasites, fungi, and toxins. Cancer: A term for diseases in which malignant cells divide without control. Cancer cells can invade nearby tissues and spread through the bloodstream and lymphatic system to other parts of the body. Colony-stimulating factor (CSF): Proteins that stimulate the development and growth of blood cells. Neupogen® (filgrastim), Neulasta® (pegfilgrastim), and Leukine® (sargramostim) are colony-stimulating factors that are used to mobilize stem cells from the bone marrow into the bloodstream prior to apheresis. These may also be used after the transplant to hasten blood count recovery, or to treat low white cell count caused by therapy. Cytokine: A protein that circulates in the bloodstream, usually in response to infection. Cytokines can stimulate or inhibit the growth or activity in other cells. 14
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Disease progression: See “Progressive disease.” Electrolytes: Minerals in your blood and other body fluids that carry an electrical charge and are essential for life. Electrolytes include sodium, potassium, calcium, magnesium, chloride, phosphate, and bicarbonate. They affect the amount of water in the body, the acidity of the blood (pH), nerve and muscle function (including the heart), and other important processes. Generic drug name: A brand name identifies a drug as property of the company that receives approval for it from a governmental regulatory agency, such as the U.S. Food and Drug Administration (FDA). After a drug goes “off patent,” other companies may make generic versions of the drug under a generic name that refers to the chemical makeup of a drug. Growth factors: Drugs that stimulate blood stem cells to both grow and be released into the bloodstream. High-risk multiple myeloma (HRMM): Myeloma that is more likely to relapse quickly after treatment or to be refractory to treatment, as defined by the cytogenetic (chromosomal) abnormalities t(4;14), t(14;16), t(14;20), del 17p, and 1q gain, along with Revised International Staging System (R-ISS) Stage III disease, and/or a high-risk gene expression profile (GEP) signature. Immune system: A complex network of cells, tissues, organs, and the substances they make. The immune system helps the body defend itself by destroying infected and diseased cells and removing cellular debris, while protecting healthy cells. Immunoglobulin (Ig): A protein produced by plasma cells; an essential part of the body’s immune system. Immunoglobulins attach to foreign substances (antigens) and assist in destroying them. The classes (isotypes) of immunoglobulins are IgG, IgA, IgD, IgE, and IgM. Each type of immuno globulin has a different function in the body. See “Antibody” and “Antigen.” • I gG, IgA – The two most common types of myeloma. The G and A refer to the immunoglobulin heavy chain produced by the myeloma cells. • I gD, IgE – These types of myeloma occur less frequently. • I gM – This is a rare type of myeloma. IgM myeloma is not the same as Waldenström macroglobulinemia. Immunomodulatory agent: A drug that can modify, enhance, or suppress the functioning of the immune system. An immunomodulatory agent is sometimes called an “immunomodulatory drug (IMiD®).” Immunomodulatory drug: See “Immunomodulatory agent.” Infusion-related reaction (IRR): 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. myeloma.org
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Reactions are often flu-like, and include nasal congestion, fever, chills, cough, throat irritation, shortness of breath, low blood pressure, nausea, and rash. See “Administration-related reaction (ARR)” and “Cytokine.” Intravenous (IV) infusion: Administered into a vein. Lymphocytes: B cells (B lymphocytes), T cells (T lymphocytes), and natural killer (NK) cells that together constitute 30% of white blood cells (WBC). Median: The mean (middle) of two central numbers in a series of numbers. For example, “median progression-free survival (mPFS)” means that half the patients had remissions that were shorter and half the patients had remissions that were longer than the mPFS. Monoclonal antibody: An antibody manufactured in a lab rather than produced in the human body. Monoclonal antibodies are specifically designed to find and bind to cancer cells and/or immune system cells for diagnostic or treatment purposes. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to tumor cells. Multiple myeloma: A cancer of the bone marrow plasma cells, white blood cells that make antibodies. Cancerous plasma cells are called myeloma cells. Natural killer (NK) cell: NK cells, also known as large granular lymphocytes, are a type of white blood cell. They are responsible for tumor surveillance; able to recognize cells that have been transformed by tumors and to induce a strong response against tumors through the release of cytokines. Unlike cytotoxic T cells, NK cells can do this without the need of a “trigger” antigen on the tumor. This can result in a faster defensive response. In patients with active myeloma, NK cells are reduced both in number and in function. Neuropathy: A feeling of numbness, tingling, burning, and/or pain caused by nerve damage. See “Peripheral neuropathy.” Neutropenia: A reduced level of neutrophils, a type of white blood cell necessary to combat bacterial infection. Over-the-counter (OTC) medications: OTC medications can be purchased without a prescription. Peripheral neuropathy (PN): Peripheral neuropathy is a serious condition that affects nerves in the hands, feet, lower legs, and/or arms. Patients may experience PN from the effects of the myeloma itself and/or from treatments for myeloma. Symptoms may include a feeling of numbness, tingling, burning, and/or pain. 16
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Progression-free survival (PFS): The length of time during and after the treatment of myeloma that a patient lives with the disease but the myeloma does not get worse. In a clinical trial, PFS is one way to measure how well the treatment is working. See “Progressive disease.” Progressive disease: Myeloma that is becoming worse or relapsing, as documented by tests. Defined as an increase of ≥ 25% from the lowest confirmed response value in the myeloma protein level and/or new evidence of disease. Proteasome: A joined group (“complex”) of enzymes (“proteases”) that break down the damaged or unwanted proteins in both normal cells and cancer cells into smaller components. Proteasomes also carry out the regulated breakdown of undamaged proteins in the cell, a process that is necessary for the control of many critical cellular functions. These smaller protein components are then used to create new proteins required by the cell. This is important for maintaining balance within the cell and for regulating cell growth. Proteasome inhibitor: Any drug that interferes with the normal function of the proteasome. See “Proteasome.” Refractory: Disease that is no longer responsive to standard treatments. Myeloma is refractory in patients who have had progressive disease either during treatment or within 60 days following treatment. Most clinical trials for advanced disease are for patients with relapsed and/or refractory myeloma. Relapse: The reappearance of signs and symptoms of myeloma 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. Most clinical trials for advanced myeloma are for patients with relapsed and/or refractory disease. Response or remission: Interchangeable terms to describe the complete or partial disappearance of the signs and symptoms of cancer. • S tringent complete response (sCR) – sCR is CR (as defined below) plus normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence. •C omplete response (CR) – For myeloma, CR is negative immunofixation on serum (blood) and urine, and disappearance of any soft tissue plasmacytomas, and ≤ 5% plasma cells in bone marrow. CR is not the same as a cure. •V ery good partial response (VGPR) – VGPR is less than CR. VGPR is serum M-protein and urine M-protein detectable by immunofixation but not myeloma.org
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on electrophoresis, or 90% or greater reduction in serum M-protein, plus urine M-protein less than 100 mg per 24 hours. •P artial response (PR) – PR is a level of response in which there is at least a 50% reduction in M-protein, and reduction in 24-hour urinary M-protein by at least 90% (or to less than 200 mg per 24 hours). Side effect: An unwanted or unexpected effect caused by a drug. Also known as adverse reaction or adverse event (AE). Tumor: An abnormal mass of tissue that results from excessive cell division. In myeloma, a tumor is referred to as a plasmacytoma. White blood cells (WBC): General term for a variety of leukocytes responsible for fighting invading germs, infections, and allergy-causing agents. These cells begin their development in bone marrow and then travel to other parts of the body. Specific white blood cells include neutrophils, basophils, eosinophils, lymphocytes, and monocytes.
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Connect. Be Informed. Take Charge. INTERACTIVE RESOURCES AT A GLANCE Use the hyperlinks and web addresses included in this publication for quick access to resources from the IMF.
infoline.myeloma.org Contact the IMF InfoLine with your myeloma-related questions and concerns
medications.myeloma.org Learn about FDA-approved therapies for myeloma
diversity.myeloma.org Diversity and inclusion are integral aspects of the myeloma community
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