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 more than 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 .
You are not alone
The International Myeloma Foundation (IMF) 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 members.
We achieve this through a broad range of resources available on our website myeloma.org, and through numerous programs and services such as seminars, webinars, workshops, and the IMF InfoLine, which 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.
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 doctor, it is important and helpful to learn about myeloma, as well as its treatment options and supportive care measures.
The IMF’s Understanding-series publications address treatments for myeloma, supportive care measures, and the tests that are used to diagnose, monitor, and assess disease status throughout its course.
This booklet discusses Kyprolis® (also known as carfilzomib, its generic drug name). Kyprolis is the second agent in a drug class called proteasome inhibitors approved by the U.S. Food and Drug Administration (FDA) in 2012 for the treatment of myeloma. Velcade® (bortezomib) is the first proteasome inhibitor approved by the FDA in 2003.
If you are newly diagnosed with myeloma, we suggest that you read the IMF’s publication Patient Handbook for the Newly Diagnosed, which will help you to better understand this complex disease.
To learn about myeloma in later disease settings, read the IMF’s publication Concise Review of Relapsed and Refractory Myeloma.
Words in bold+blue type are explained in the “Terms and definitions” section at the end of this booklet. A more comprehensive glossary can be found in the IMF’s publication Understanding Myeloma Vocabulary 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 format at publications.myeloma.org.
How Kyprolis works
Kyprolis works by blocking the activity of enzyme complexes called proteasomes. Both normal cells and cancer cells contain proteasomes, which break down damaged and unwanted proteins 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.
Kyprolis forms an irreversible bond with the proteasomes in myeloma cells, and those myeloma cells stop dividing and undergo apoptosis, a cellular process leading to the death of a cell. The myeloma cells also stop producing chemicals to stimulate other cancer cells. Myeloma cells are more sensitive to proteasome inhibition than normal cells, so the myeloma cells die while normal cells are able to recover.
Indications for treatment with Kyprolis
Kyprolis is approved by the FDA in the following settings:
¡ Kyprolis in combination with the steroid dexamethasone [Kd] for the treatment of patients with relapsed or refractory myeloma who have received 1 to 3 prior lines of therapy.
¡ Kyprolis as a single agent for the treatment of patients with relapsed or refractory myeloma who have received 1 or more prior lines of therapy.
¡ Kyprolis in combination with immunomodulatory agent Revlimid® (lenalidomide) plus dexamethasone [KRd] for the treatment of patients with relapsed or refractory myeloma who have received 1 to 3 prior lines of therapy.
¡ Kyprolis in combination with monoclonal antibody Darzalex® (daratumumab) or Darzalex Faspro® (daratumumab + hyaluronidasefihj) plus dexamethasone for the treatment of patients with relapsed or refractory myeloma who have received 1 to 3 prior lines of therapy.
¡ Kyprolis in combination with monoclonal antibody Sarclisa® (isatuximab-irfc) plus dexamethasone [Isa-Kd] for patients with relapsed or refractory myeloma who have received 1 to 3 prior lines of therapy.
Kyprolis dose and administration
Kyprolis is a freeze-dried (lyophilized) powder that must be reconstituted (dissolved) before it is given by intravenous (IV) infusion at a doctor’s office, hospital, or clinic. At the discretion of the treating physician, hydration may
be given before and after each dose of Kyprolis, based upon the patient’s tolerance of Kyprolis, the dose of Kyprolis, and the duration of infusion time. Caution must be exercised to avoid fluid overload.
In patients with mild or moderate hepatic (liver) impairment, the dose of Kyprolis must be reduced by 25%.
You and your doctor will determine which Kyprolis dosing regimen is best for you from among the following options:
Once-weekly Kd regimen
20/70 mg/m2 by 30-minute infusion:
¡ Each cycle is 28 days.
¡ Kyprolis is given at 20 mg/m2 on day 1 of cycle 1, then 70 mg/m2 is given on days 8 and 15. For cycle 2 and thereafter, Kyprolis is given at 70 mg/m2 on days 1, 8, and 15.
No Kyprolis is given on days 16–28 of any cycle.
¡ Dexamethasone is given at a dose of 40 mg on days 1, 8, 15, and 22 of cycles 1–9. Thereafter, dexamethasone is given only on days 1, 8, and 15 of each cycle.
Twice-weekly Kd regimen or Kyprolis monotherapy
20/56 mg/m2 by 30-minute infusion:
¡ Each cycle is 28 days.
¡ Kyprolis is given at 20 mg/m2 on days 1 and 2 of cycle 1 and, if tolerated, at 56 mg/m2 on days 8, 9, 15, and 16. During cycles 2–12, Kyprolis is given at 56 mg/m2 on days 1, 2, 8, 9, 15, and 16. For cycle 13 and thereafter, Kyprolis is given at 56 mg/m2 on days 1, 2, 15, and 16. No Kyprolis is given on days 17–28 of any cycle.
¡ Dexamethasone is not given with Kyprolis monotherapy. If you are on the Kd regimen, dexamethasone is given at 20 mg per day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each cycle.
Twice-weekly Kyprolis monotherapy
20/27 mg/m2 by 10-minute infusion:
¡ Each cycle is 28 days.
¡ Kyprolis is given at a dose of 20 mg/m2 on cycle 1, days 1 and 2. If tolerated, the dose is escalated to 27 mg/m2 on days 8, 9, 15, and 16 of the first cycle. In cycles 2–12, Kyprolis is given at 27 mg/m2 on days 1, 2, 8, 9, 15, and 16. For cycle 13 and thereafter, Kyprolis is given at 27 mg/m2 on days 1, 2, 15, and 16.
No Kyprolis is given on days 17–28 of any cycle.
Twice-weekly KRd regimen
20/27 mg/m2 by 10-minute infusion:
¡ Each cycle is 28 days.
¡ Kyprolis is given during cycle 1 at 20 mg/m2 on days 1 and 2, and if tolerated, at 27 mg/m2 on days 8, 9, 15, 16.
In cycles 2–12, Kyprolis is given at 27 mg/m2 days 1, 2, 8, 9, 15, and 16. For cycle 13 and thereafter, Kyprolis is given at 27 mg/m2 on days 1, 2, 15, and 16.
No Kyprolis is given on days 17–28 of any cycle.
¡ Revlimid is given at 25 mg on days 1–21 of each cycle.
¡ Dexamethasone is given at 40 mg on days 1, 8, 15, and 22 of each cycle.
Once-weekly DKd regimen
20/70 mg/m2 by 30-minute infusion:
¡ Each cycle is 28 days.
¡ Kyprolis is given at 20 mg/m2 on day 1 of cycle 1 and, if tolerated, at 70 mg/m2 on days 8 and 15. Cycles 2–7 and thereafter, Kyprolis is given at 70 mg/m2 on days 1, 8, and 15.
¡ Darzalex IV is given at a dose of 8 mg/kg on days 1 and 2 of cycle 1 and, if tolerated, at 16 mg/kg on days 8, 15, and 22; alternatively, Darzalex Faspro SQ can be given as an abdominal injection under the skin at a dose of 1,800 mg/30,000 units on days 1, 8, 15, and 22.
On days 1, 8, 15, and 22 of cycle 2, Darzalex IV is given at a dose of 16 mg/kg or Darzalex Faspro SQ is given at a dose of 1,800 mg/30,000 units.
On days 1 and 15 of cycles 3–6, Darzalex IV is given at a dose of 16 mg/kg or Darzalex Faspro SQ is given at a dose of 1,800 mg/30,000 units.
On Day 1 of cycle 7 and thereafter, Darzalex IV is given at a dose of 16 mg/kg or Darzalex Faspro SQ is given at a dose of 1,800 mg/30,000 units.
¡ Dexamethasone is given 30 minutes to 4 hours before Kyprolis and 1–3 hours before Darzalex IV. Dexamethasone is given at a dose of 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of cycles 1 and 2.
During cycles 3–6, dexamethasone is given at 20 mg on days 1 and 2; then 40 mg on day 8; then 20 mg on days 15, 16; then 40 mg on day 22.
For cycle 7 and thereafter, dexamethasone is given at 20 mg on days 1 and 2; then 40 mg on days 8, 15, and 22. Alternatively, dexamethasone can be given on the same schedule as in the twice-weekly DKd regimen.
Patients aged > 75 years receive dexamethasone at 20 mg after the first week of cycle 1.
Twice-weekly DKd regimen
20/56 mg/m2 by 30-minute infusion:
¡ Each cycle is 28 days.
¡ Kyprolis is given on days 1, 2, 8, 9, 15, and 16 of each cycle. For cycle 1 only, patients receive a 20-mg/m2 dose of Kyprolis on days 1 and 2. For all subsequent cycles thereafter, Kyprolis is administered at a dose of 56 mg/m2.
¡ Darzalex is given at a dose of 16 mg/kg on days 1, 8, 15, and 22, of cycles 1 and 2, every 2 weeks during cycles 3–6, and every 4 weeks during cycle 7 and thereafter. At the discretion of the treating doctor, there is an option of splitting the initial dose of Darzalex into two 8-mg/kg doses to be given on cycle 1, day 1 and cycle 2, day 2.
¡ Dexamethasone is given at a dose of 40 mg on days 1, 8, 15, and 22 of each cycle. During weeks when patients receive Kyprolis and/or Darzalex, a split dose of 20 mg each of dexamethasone is given.
Once-weekly Isa-Kd regimen
20/56 mg/m2 by 30-minute infusion:
¡ Each cycle is 28 days.
¡ Kyprolis is given at 20 mg/m2 once-weekly in cycle 1, then once every other week at 56 mg/m2 during in subsequent cycles.
¡ Sarclisa is given at 10 mg/kg as an IV infusion once-weekly in cycle 1 on days 1, 8, 15, and 22.
In cycle 2 and beyond, the Sarclisa infusion is administered on days 1 and 15. The first infusion takes about 3–4 hours, the second infusion is about 2 hours, and the subsequent infusions are typically 75 minutes.
¡ Dexamethasone is given at a dose of 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each cycle as an IV infusion on days of Sarclisa or Kyprolis IV infusions, and taken orally by tablet on other days.
Twice-weekly Isa-Kd regimen
20/56 mg/m2 by 30-minute infusion:
¡ Each cycle is 28 days.
¡ Kyprolis is given at 20 mg/m2 on days 1 and 2 in cycle 1 to evaluate tolerability, then at the therapeutic dose of 56 mg/m2 on days 8 and 9 of cycle 1. Treatment schedule for subsequent cycles is Kyprolis at 56 mg/m2 given twice-weekly for 3 weeks, followed with a 12-day rest period.
¡ Sarclisa is given at 10 mg/kg as an IV infusion once-weekly in cycle 1 on days 1, 8, 15, and 22. In cycle 2 and beyond, the Sarclisa infusion is administered on days 1 and 15. The first infusion takes about 3–4 hours, the second infusion is about 2 hours, and the subsequent infusions are typically 75 minutes.
¡ Dexamethasone is given at a dose of 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each cycle as an infusion on days of Sarclisa or Kyprolis IV infusions, and taken orally by tablet on other days.
Treatment with Kyprolis may be continued until disease progression or unacceptable toxicity. Your doctor will evaluate your response to Kyprolis and your tolerance of your medications to determine how many cycles of treatment are right for you.
Your doctor may make schedule adjustments, reduce your dose of Kyprolis, or stop treatment temporarily until a side effect improves, and then resume again. A side effect is any unwanted or unexpected effect caused by a drug, also known as an adverse reaction or adverse event (AE).
Cautions with the use of Kyprolis
Caution must be exercised with higher doses of Kyprolis. You must be monitored carefully for infusion-related reactions (IRR), which can occur immediately following an infusion or up to 24 hours after. Complications may include fever, chills, joint pain, muscle pain, facial flushing, facial swelling, vomiting, weakness, shortness of breath, low blood pressure, fainting, chest tightness, or chest pain. It is essential that you promptly report to your doctor any side effects that you experience in the days after your infusion of Kyprolis.
Administration of dexamethasone prior to the infusion of Kyprolis reduces the incidence and severity of IRR. Additional precautions with the use of Kyprolis include the following:
¡ Talk with your doctor about being pretreated with dexamethasone prior to your cycle 1 dose and if infusion reaction symptoms develop or reappear.
¡ Your doctor will give you instructions specific to your case about how much water you should drink before your first infusion of Kyprolis.
¡ Talk with your doctor about receiving medication to prevent blood clots if you are taking Kyprolis in combination with dexamethasone or with Revlimid + dexamethasone. Your doctor will choose the appropriate medication for you based on an assessment of your individual risk factors for blood clots.
¡ Talk with your doctor about receiving antiviral therapy to decrease the risk of herpes zoster.
¡ If you are receiving hemodialysis for kidney failure, you should receive Kyprolis after the hemodialysis procedure.
¡ Kyprolis can cause harm to a fetus if it is administered to a pregnant woman. Females of childbearing potential should avoid becoming pregnant during treatment with Kyprolis, and should not take Kyprolis while breastfeeding.
Possible side effects of Kyprolis
Good communication with your doctor is extremely important while you are receiving treatment for myeloma. Discuss your questions or concerns with your doctor, and alert your doctor promptly if you experience any side effects. The most common side effects, those seen in 30% or more of the patients who received Kyprolis in clinical trials, include fatigue, anemia, nausea, thrombocytopenia, dyspnea, diarrhea, and fever. Kyprolis may also cause dizziness, fainting, and/or a drop in blood pressure, so caution is advised if you are operating machinery, including automobiles. In clinical trials, the incidence of side effects was greater in patients age 75 or older.
Serious adverse events reported to the FDA by researchers during clinical trials of combination therapies with Kyprolis included the following:
¡ Renal (kidney) insufficiency, including renal failure, occurred in approximately 9% of patients treated with Kyprolis.
¡ Cardiac failure events, such as congestive heart failure, pulmonary edema, and decreased heart ejection fraction occurred in 8% of patients. Arrhythmias occurred in 8% of patients, the majority of which were atrial fibrillation and sinus tachycardia.
¡ Pulmonary arterial hypertension (abnormally high blood pressure in the arteries of the lungs) occurred in 2% of patients.
¡ Liver failure, including fatal cases, occurred in less than 1% of patients.
Some occurrences of kidney failure in myeloma patients receiving Kyprolis have resulted in death. Acute renal failure was reported more frequently in patients with advanced relapsed and refractory myeloma who received Kyprolis as a single therapy. Your kidney function will be monitored regularly while you are taking Kyprolis, and your dose of Kyprolis will be reduced or withheld as needed.
Death due to cardiac arrest has occurred within a day of Kyprolis administration. Patients with pre-existing heart conditions may be at greater risk for cardiac complications. Although underlying heart disease does not exclude use of Kyprolis, patients with New York Heart Association (NYHA) Class III and IV congestive heart failure, as well as those with uncontrolled conduction abnormalities or a history of heart attack within the previous six months, were excluded from clinical trials. Prescribing information for Kyprolis recommends that patients be monitored for cardiac complications and managed promptly.
Kyprolis can cause other rare but serious side effects. You must report any changes in your health promptly to your medical team so that they can
monitor your signs and symptoms. Contact your doctor immediately if you experience fever, chills, shivering, chest pain, cough, swelling of the feet or legs, bleeding, bruising, weakness, headaches, confusion, seizures, loss of sight, shortness of breath, dizziness, lightheadedness, fainting, or any other potential side effects.
Any concerns or questions about these issues should be discussed with your doctor or nurse, who can provide more information in greater detail about these and other possible side effects. Speak with your doctor or nurse if you notice ANY changes in your health while you are taking Kyprolis or any other medication.
Fatigue
Fatigue is the most common side effect associated with Kyprolis therapy, and one that can appear with increasing severity over time. For further information about fatigue, read the IMF’s publication Understanding Fatigue.
Prevention and treatment of fatigue
Discuss your fatigue with your doctor and healthcare team. Management of fatigue may include supportive care as determined by your physician. The effects of fatigue may be minimized by maintaining:
¡ A moderate level of activity, neither too much nor too little,
¡ A healthy diet and proper fluid intake,
¡ A consistent sleeping schedule with enough rest.
Anemia
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. Many newly diagnosed myeloma patients have anemia. Anemia may or may not develop over the course of treatment with Kyprolis.
Prevention and treatment of anemia
Your doctor will determine how to treat your anemia. Options may include adjusting medication, blood transfusions, or erythropoietic (red blood cell-making) agents.
Nausea
Nausea may occur while taking Kyprolis, but is typically not severe. If vomiting occurs and leads to dehydration, a patient may experience dizziness, lightheadedness, or fainting. Medical treatment may be required for dehydration.
Prevention and treatment of nausea
Precautions should be taken to prevent dehydration caused by vomiting. Drink a sufficient amount of water and other fluids. Seek medical advice if you experience dizziness, lightheadedness, or fainting. Your physician may administer anti-emetic medication (to prevent vomiting) or intravenous hydration, as required.
Thrombocytopenia
Thrombocytopenia is defined as 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 varies from laboratory to laboratory. For example, at Mayo Clinic the “normal” level is ≥ 150,000 platelets per microliter of circulating blood. If the platelet count is less than 50,000, bleeding problems could occur. Major bleeding is usually associated with a reduction to less than 10,000.
Patients taking Kyprolis often experience thrombocytopenia. The platelet level decreases with treatment but, after the required interval between doses, should return to the baseline level by the beginning of the next cycle.
Prevention and treatment of thrombocytopenia
You should inform your physician if you experience excessive bruising or bleeding. Management may include lowering or withholding the next dose of Kyprolis. Platelet transfusions may be ordered at your doctor’s discretion.
Dyspnea
Dyspnea is the medical term for shortness of breath, often described as an intense tightening in the chest, air hunger, difficulty breathing, or breathlessness. Dyspnea can be caused by a host of medical problems, including anemia, pneumonia, or a pulmonary embolism.
It is urgent that you contact your doctor if there is a sudden change in your breathing. There have been reports of heart and lung disorders in patients receiving Kyprolis, and shortness of breath can be a sign of a serious problem and must be reported to your doctor immediately.
Prevention and treatment of dyspnea
Appropriate measures to prevent and treat shortness of breath depend on the cause of this problem. Your doctor will assess your heart and lungs and may order more tests before deciding upon the course of action.
Diarrhea
Diarrhea is defined as 3 or more loose stools per day. Severe diarrhea is defined as 7 or more loose stools per day, requiring treatment with
intravenous fluids or hospitalization. Diarrhea may occur while taking Kyprolis. Dizziness, lightheadedness, 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, lightheadedness, or fainting. Your physician may administer antidiarrheal medication or IV hydration, as required.
Fever
An oral temperature greater than 100.4°F (38°C) needs to be further evaluated immediately. Fever can signal bacterial or viral infection, an adverse reaction to a drug, or in rare cases, an aggressive myeloma relapse. Since fever can be the sign of a life-threatening condition, you should report this problem immediately. The combination of fever and shortness of breath is of special concern. If this occurs, it is urgent that the patient is seen by a healthcare professional to receive immediate treatment.
Prevention and treatment of fever
Your doctor will perform tests to determine the cause of the fever and will take appropriate action, which may include one or more of the following:
¡ Antibiotic therapy,
¡ Antiviral therapy,
¡ Treatment with acetaminophen,
¡ Hydration,
¡ Change in therapy.
Other possible side effects of Kyprolis
Less frequent side effects that may occur with Kyprolis include tumor lysis syndrome (TLS), lung disorders, and liver problems. Alert your doctor promptly if you experience the following:
¡ Shortness of breath,
¡ Flu-like symptoms (for example, fever, chills, or shivering),
¡ Chest pain,
¡ Cough,
¡ Dizziness, lightheadedness, or fainting spells,
¡ Swelling of the feet, ankles, or legs.
Good communication with your healthcare team is essential while you are receiving therapy for myeloma. Ask your doctor for a number you can call if you need immediate help, especially after office hours and on the
weekend. An important part of being a patient is to report side effects promptly and clearly. The IMF is here to help facilitate the best possible dialogue with your healthcare team.
Kyprolis in clinical trials
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. Kyprolis is currently being studied in numerous clinical trials throughout the myeloma disease course and as part of different combination therapies.
In December 2023, the results from the ISKIA phase III clinical trial were presented at a plenary session of the annual meeting of the American Society of Hematology (ASH). The study evaluated 302 patients with newly diagnosed multiple myeloma (NDMM) who were eligible for an autologous stem cell transplant (ASCT). Patients were randomized to two study arms with 151 patients in each arm. One arm received Kyprolis + Revlimid + dexamethasone [KRd] and the other arm received Sarclisa® (isatuximab-irfc) + KRd [Isa-KRd].
This clinical trial assessed efficacy and safety of Isa-KRd as pre-ASCT induction therapy and post-ASCT consolidation therapy. Compared to KRd alone, Isa-KRd induction and consolidation significantly increased the rates of MRD-negativity in every treatment phase and with no new safety concerns, including in patients with high-risk multiple myeloma (HRMM).
Kyprolis is being studied in numerous clinical trials as part of a wide spectrum of combination therapies and across myeloma disease settings. Contact the IMF InfoLine or visit clinicaltrials.gov for up-to-date 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 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 glossary 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.”
Baseline: The initial known data that is gathered and used for comparison with later data.
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.
Cell: The basic unit of any living organism. Millions of microscopic cells comprise each organ and tissue in the body.
Congestive heart failure: A condition that occurs when the heart’s pumping function is weakened, causing a series of events that result in the body retaining fluid and salt. If fluid builds up in the arms, legs, feet, ankles, lungs, or other organs, the body becomes congested.
Consolidation therapy: Treatment that may be given to deepen the patient’s response after an autologous stem cell transplant (ASCT). Usually, consolidation therapy is the same regimen used for induction 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.
Drug class: A group of medications that have a similar chemical structure or a similar mechanism of action (MoA).
Enzyme: A protein molecule manufactured by a cell. An enzyme acts as a catalyst that increases the rate of a specific biochemical reaction in the body.
Frontline therapy: A general term for the initial treatment used in an effort to achieve response in a newly diagnosed myeloma patient. See “ Induction therapy ” and “ Response or remission.”
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.
Herpes zoster: Also called “shingles,” herpes zoster is caused by the reactivation of the varicella-zoster virus (VZV), the same virus that causes varicella (also called “chickenpox”). When reactivated, the herpes zoster infection frequently affects nerves.
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.
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®).”
Induction therapy: The initial treatment given to a patient in preparation for an autologous stem cell transplant (ASCT). See “ Frontline therapy ” and “ Line of therapy.”
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. 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.
Line of therapy: A term used to calculate the number of therapies a patient has received. A line of therapy is 1 or more complete cycles of a regimen that can consist of a single agent, a combination of several drugs, or a planned sequential therapy of various regimens. Also see “ Induction therapy.”
Minimal residual disease (MRD): The presence of residual tumor cells after treatment has been completed and complete response (CR) has been attained. Even patients who have attained a stringent CR (sCR) may have MRD. Highly sensitive testing methods are able to detect 1 myeloma cell among 1,000,000 sampled cells in blood or bone marrow. See “MRD-negative.”
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.
MRD-negative: Minimal residual disease-negative. Depending on the test, not even one myeloma cell found in 100,000 or 1,000,000 sampled bone marrow plasma cells. See “Minimal residual disease (MRD).”
Multiple myeloma: A cancer of the bone marrow plasma cells, white blood cells that make antibodies. Cancerous plasma cells are called myeloma cells.
Platelets: One of the three major types of blood cells, the others being red blood cells and white blood cells. Platelets plug up breaks in the blood vessel walls and release substances that stimulate blood clot formation. Platelets are the major defense against bleeding. Also called thrombocytes.
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.”
Proteins: Substances composed of amino acids. Proteins are an essential part of all living organisms, especially as structural components of body tissues such as muscle, hair, collagen, etc., as well as enzymes and antibodies.
Red blood cells (RBC): Also called erythrocytes, these cells in the blood contain hemoglobin, deliver oxygen to all parts of the body, and take away carbon dioxide. Red blood cell production is stimulated by a hormone (erythropoietin) produced by the kidneys. Myeloma patients with damaged kidneys don’t produce enough erythropoietin and can become anemic. Myeloma patients can also become anemic because of myeloma cells’ effect on the ability of bone marrow to make new red blood cells.
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.
• Stringent 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.
• Complete 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.
• Very good partial response (VGPR) – VGPR is less than CR. VGPR is serum M-protein and urine M-protein detectable by immunofixation but not on electrophoresis, or 90% or greater reduction in serum M-protein, plus urine M-protein less than 100 mg per 24 hours.
• Partial 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).
Steroid: A type of hormone. Steroidal hormones are produced by the body. Synthetic analogues (equivalents) of some steroids can be manufactured in a laboratory. Dexamethasone, prednisone, and methylprednisolone are synthetic steroids that have multiple effects and are used for many conditions, including myeloma.
Thrombocytopenia: 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.
Tumor lysis syndrome (TLS): A disorder caused by the break-down products of dying cancer cells, which can overwhelm the kidneys and lead to kidney failure. TLS can occur when a patient responds very quickly and deeply to therapy. TLS is usually treated with allopurinol, a treatment for gout.
INTERACTIVE RESOURCES AT A GLANCE
Diversity and inclusion are integral aspects of the myeloma community diversity.myeloma.org Contact the IMF InfoLine with your myeloma-related questions and concerns infoline.myeloma.org Learn about the growing number of FDA-approved myeloma therapies medications.myeloma.org
