Understanding Fatigue in Myeloma
The International Myeloma Foundation (IMF) is the global leader in multiple myeloma, reaching more than 525,000 patients in 140 countries. The IMF mission is to improve the quality of life of myeloma patients while working toward prevention and a cure. The IMF vision is to realize a world where every myeloma patient can live life to the fullest, unburdened by the disease. Since 1990, the IMF has been serving the myeloma community through the following four pillars:
RESEARCH At the IMF, finding a cure for myeloma is our top priority. The IMF Scientific Advisory Board (SAB) of leading myeloma experts identifies key opportunities to drive research forward. The IMF Black Swan Research Initiative® is pushing the boundaries with early screening for a precursor condition of myeloma as well as cure-focused myeloma clinical trials. The IMF International Myeloma Working Group (IMWG) provides trusted guidelines for diagnosing, treating, and managing myeloma. The IMF also funds innovative research through its Brian D. Novis Research Grants.
EDUCATION Myeloma is a complex and unique journey for each patient. The IMF offers hundreds of free publications in multiple languages to help navigate the myeloma journey. IMF seminars, webinars, and workshops directly connect patients with expert clinicians. The IMF Nurse Leadership Board (NLB) provides recommendations for managing myeloma. The IMF M-Power Project works to break down barriers and ensure health equity in underserved populations.
SUPPORT The IMF offers more than 160 myeloma support groups across North America, including specialized groups for Spanish-speakers, people with smoldering disease, care partners of patients with myeloma, and patients without care partners. The IMF InfoLine helps with your myeloma-related questions. The IMF “Myelo” AI chatbot helps you find the right resources. You don’t have to face myeloma alone. Studies show that social support can greatly improve the quality of life of people with cancer.
ADVOCACY In the U.S., the IMF Advocacy team represents your interests at the federal and state levels. Internationally, the IMF Global Myeloma Action Network (GMAN) works to improve patient access to treatments.
Visit myeloma.org or contact the IMF InfoLine at 1.818.487.7455 (worldwide) or 1.800.452.CURE (U.S. and Canada), or infoline@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. If you have myeloma, it is important and helpful for you to learn about your disease, its treatment options, and supportive care measures in order to play an active role in your own medical care and to make good decisions about your care in partnership with your doctor.
If you are a patient with myeloma, we suggest that you read the IMF’s publication, Patient Handbook for Multiple Myeloma, which will help you to better understand this disease. In addition, this booklet will direct you to resources that may be relevant in your particular case. All IMF publications are free-of-charge and can be read, downloaded, or requested in printed format at publications.myeloma.org.
The IMF’s Understanding-series publications address specific drugs, drug classes, and combination therapies used to treat myeloma. These booklets also discuss supportive care measures that may help manage the symptoms and side effects of myeloma and its treatments. The IMF’s publication, Understanding Your Test Results, explains how myeloma is diagnosed, monitored, and assessed throughout the disease course.
Words in bold+blue type are explained in the IMF’s companion publication, Understanding Myeloma Vocabulary, a comprehensive glossary that also can be helpful in discussions with your doctor. Myeloma is complicated, but the language that describes it doesn’t have to be hard to understand.
If you are reading this booklet in electronic format, the light blue links will take you to the corresponding resources.
This booklet discusses fatigue in patients with myeloma. Fatigue can be caused by the myeloma itself and by treatment for myeloma, as well as by other medical conditions and their treatment.
Fatigue in patients with myeloma
In healthy people, fatigue is understood as exhaustion or tiredness that interferes to some extent with normal everyday activities. It usually occurs after strenuous or prolonged exertion of some kind and is temporary. Rest and refraining from strenuous activity can help restore energy and make a healthy person feel better.
Fatigue that is related to cancer and its treatments is different and more severe than normal fatigue and tends to last longer. Simply resting does not alleviate this type of fatigue, which has been defined by the National Comprehensive Cancer Network (NCCN) as “a distressing, persistent, subjective sense of tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning.”
Cancer-related fatigue (CRF) may be associated with difficulty concentrating, dizziness, or a disinterest in what is going on around you. Asthenia, a condition in which the body lacks or has lost strength either as a whole or in any of its parts, often accompanies or is a component of CRF.
In patients with myeloma, fatigue and asthenia can be the result of many individual or collective causes, including the myeloma itself and/or treatments for myeloma, as well as other medical problems and/or their treatments.
Report your fatigue to your doctor
Do not think that your fatigue or weakness is not important enough to discuss with your doctor. Fatigue or weakness may be a consequence of your diagnosis or treatment, but this doesn’t mean that it cannot be prevented or managed. Be thorough in reporting your experience to your doctor, and include the following descriptors if applicable:
¡ All of your other conditions or illnesses,
¡ All prescription and over-the-counter drugs you are taking,
¡ Changes in appetite, diet, and/or weight,
¡ Changes in activity level, daily routine, and/or sleep pattern,
¡ Circumstances or time of day or when your fatigue is most noticeable,
¡ Presence and location of physical pain,
¡ Emotional stress, anxiety, or depression,
¡ Lack of energy and motivation,
¡ Decreased libido,
¡ Swelling in the legs or ankles,
¡ Shortness of breath,
¡ Rapid heartbeat,
¡ Headache,
¡ Dizziness,
¡ Chills.
Your doctor will grade and classify your fatigue
Keep track of your fatigue and note how it impairs your quality of life. Your doctor needs your input in order to assess the severity of your fatigue and the extent to which it prevents you from performing the normal activities of daily living.
Your fatigue will be rated on a scale from 0 (no fatigue) to 10 (worst fatigue imaginable). In addition, your fatigue will be classified as mild (0 to 3), moderate (4 to 6), or severe (7 to 10).
Myeloma-related fatigue
The most common causes of fatigue in myeloma patients are myelomainduced anemia, high levels of cytokines, and persistent pain. Each of these causes can result in weight loss, decreased appetite, weakness, and fatigue. When more than one issue is present at the same time, fatigue can be severe.
Anemia
Anemia is very common in myeloma patients and is often the first symptom of the disease. At least 60%–70% of newly diagnosed myeloma patients have anemia at the time of diagnosis.
If you do not have anemia when you are diagnosed with myeloma, you may experience anemia later in the disease course. Myeloma cells interfere with the blood-producing activities of the bone marrow, often leading to anemia.
Anemia is usually defined as a decrease in hemoglobin < 10 g/dL or a decrease in hemoglobin ≥ 2 g/dL from the normal level for the individual patient. Hemoglobin is a protein in red blood cells (RBC) that carries oxygen to the body’s tissues and organs. Low levels of oxygen in the body may cause shortness of breath and feelings of exhaustion.
If your doctor suspects that you have anemia, your blood will be drawn for laboratory tests. Low hemoglobin levels indicate anemia. Normal hemoglobin level reference range is 13.5–17.5 g/dL (135–175 g/L) for males and 12.0–15.5 g/dL (120–155 g/L) for females.
For newly diagnosed myeloma patients who are anemic, the first and most important thing to do is to treat the myeloma. Often, when a treatment successfully attacks and destroys myeloma cells in the bone marrow, the marrow will once again be able to make a normal number of RBCs, and your hemoglobin level will rise.
When immediate correction of the anemia is needed, blood transfusions can replace and replenish your RBCs. Transfusions have an immediate beneficial effect, but the increase in your hemoglobin levels may not be
very large and may last only for a few weeks, so repeated transfusions may be necessary. However, after a prolonged period of receiving transfusions, you may become resistant to transfusions of blood from other people.
If your fatigue is not the result of anemia, it may be challenging to diagnose. You must be proactive in reporting the signs and symptoms that you are experiencing, so that your doctor can evaluate your situation and try to identify the source(s) of your fatigue.
High levels of cytokines
Cytokines are proteins that circulate in the bloodstream. High cytokine levels are known to be a source of cancer-related fatigue. Cytokines such as interleukins, interferon, and tumor necrosis factor (TNF) are molecules that send signals within the immune system.
Cytokines are released by T cells (T lymphocytes) in response to infection or inflammation. Cytokines can stimulate the growth of cancer cells, hinder apoptosis (death) of cancer cells, and aid cancer cells in spreading to other areas of the body. The effect of cytokine release is similar to the fatigue you feel when fighting a viral illness such as the flu, but it lasts longer.
Cytokine release syndrome (CRS) is an uncontrolled immune reaction that is potentially fatal, in which cytokines become highly elevated and trigger an overwhelming immune system response. A cytokine “storm” can seriously damage body tissues and organs.
Effective anti-myeloma treatment lowers the level of cytokines in the bone marrow environment where myeloma grows.
Pain
Many myeloma patients suffer from painful bone disease or from pain related to peripheral neuropathy (PN), a serious condition that can affect 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.
Chronic, severe pain, whether from myeloma bone disease or from PN, causes fatigue. Some of the most effective pain relievers can also cause drowsiness, loss of appetite, nausea, weight loss, and headache, all adding to fatigue.
Myeloma treatment-related fatigue
According to the National Cancer Institute (NCI), fatigue is the most common side effect of cancer treatment. A side effect is an unwanted or unexpected effect caused by a treatment approach. Side effects are also called adverse reactions or adverse events (AE).
Your doctor might adjust your myeloma therapy or suggest a better time of day for it, present you with supportive care treatment options, or prescribe a stimulant to help you be more active.
Anemia
Treatments for myeloma can reduce all the blood cell counts and thus can cause anemia. If your treatment is causing anemia while your myeloma is improving, your doctor may prescribe an erythropoiesis -stimulating agent (ESA) to stimulate the production of red blood cells. ESAs are used only when there is also a chemotherapy agent in use.
ESAs carry their own side effects and risks. They should be used with caution in light of their association with increased tumor growth and reduced survival in some patients with cancer. Please also read or re-read the section on anemia on page 6.
Neutropenia
Neutropenia is a reduced level of neutrophils, a type of white blood cell necessary to combat bacterial infection. Having too few neutrophils can lead to infection. If your myeloma therapy is causing neutropenia and you develop an infection, treatment with antibiotics and antivirals or a colony-stimulating factor (CSF), which can help to treat the problem underlying the infection and fatigue and will help prevent it from occurring again.
Fever is the most common sign of neutropenia. If you have a fever, you must get immediate medical attention.
Chemotherapy
You may experience fatigue because therapy can kill healthy cells along with cancer cells, so the body expends extra energy to repair the healthy cells. If too many white blood cells (WBC) are killed during therapy, you may get an infection, contributing further to fatigue. If too many red cells are killed, anemia results. Side effects such as nausea and vomiting, insomnia, muscle wasting, and changes in mood may also cause fatigue and weakness. These side effects are common when patients undergo high-dose chemotherapy (usually melphalan) with stem cell rescue.
Newer myeloma therapies
For reasons both known and unknown, fatigue is among the most commonly reported side effects of novel therapies for myeloma. These therapies can impair the production of new blood cells, leading to anemia and infection. Another factor is increased levels of cytokines. Fatigue may improve over time with duration of some treatment as the myeloma disease burden decreases. However, fatigue may also increase over time with other treatments. Let your doctor know of any side effect you are experiencing.
Steroids
Steroids are 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. To learn about dexamethasone, the steroid used most frequently in myeloma, read the IMF’s publication Understanding Dexamethasone in the Treatment of Myeloma.
Steroids are a component of nearly all combination therapies for myeloma, because steroids appear to increase or “boost” the ability of other agents to destroy myeloma cells, thereby improving response to treatment. Patients taking doses of steroids that are sufficient to treat myeloma may experience an initial burst of energy and sleeplessness followed by a “crash” into fatigue and weakness.
Steroids are associated with many short-term and long-term side effects such as insomnia, mood changes, suppressed immune response, and muscle wasting, each of which can contribute to the feelings of fatigue and weakness. Steroids can also cause a number of other serious side effects. If you are taking steroids, you should be monitored closely, and you must report any side effects to your doctor, who can adjust your dose and schedule and assess the need for continuation of the steroid.
Radiation therapy
Radiation therapy with X-rays, gamma rays, or electrons aims to kill cancer cells. Radiation can be delivered from outside the body or from radioactive materials implanted directly into a tumor, an abnormal mass of tissue that results from excessive cell division.
Radiation therapy damages both cancer cells and healthy cells, requiring extra energy to repair cellular damage. Radiation therapy is known to cause fatigue, which usually lasts 3 to 4 weeks after the treatment ends, but may last for months and/or become worse over time.
Radiation therapy in the upper chest or neck area may affect the thyroid gland, causing hypothyroidism (low levels of thyroid hormone) that slows down metabolism so that the body does not burn calories from food fast enough to provide adequate energy.
Medications for other medical conditions
If you are being treated for other conditions while also being treated for myeloma, provide to your doctor and pharmacist a complete list of all the prescription medications and over-the-counter products that you are taking. Ask them about possible interactions and side effects, and get their guidance about setting a medication schedule that is best for you.
Drugs for the following conditions may cause or contribute to your fatigue:
¡ High blood pressure medications may slow down the pumping action of the heart as well as depress the central nervous system.
¡ Statins used to treat high cholesterol stop the production of muscle growth, and some researchers think that they also interfere with the production of energy at the cellular level.
¡ Proton pump inhibitors used to treat gastroesophageal reflux disease (GERD) and related disorders frequently lead to low levels of magnesium in the blood, which can cause loss of appetite, fatigue, and weakness.
¡ Tranquilizers (benzodiazepines) are used to treat a variety of anxiety disorders, agitation and muscle spasms, neuropathic pain, and seizures. They can cause sedation and fatigue by suppressing activity in parts of the central nervous system.
¡ Antidepressants are used not only to treat depression but are also prescribed for neuropathic pain, anxiety disorders, obsessive compulsive disorders, and some hormone-related disorders. Researchers believe that they cause fatigue through their effect on hormones and neurotransmitters in the brain. They can also lower levels of potassium, causing muscle weakness.
¡ Antibiotics can affect some people with feelings of tiredness and extreme fatigue, although researchers have not discovered why. Changes in bowel habits and food and nutrient absorption that can occur with antibiotics can cause fatigue and listlessness. The package inserts of many antibiotics (e.g., Bactrim DS®, Keflex®, Zithromax®) list fatigue or somnolence (sleepiness) as a potential side effect.
¡ Diuretics are prescribed to control high blood pressure, glaucoma, edema (fluid retention that causes swelling), and other conditions. Diuretics can interfere with the balance of electrolytes in the body. In addition to many other serious problems, electrolyte imbalances can cause extreme fatigue, muscle weakness, and pain in joints, bones, and muscles.
¡ Sleep aids interact with the same neurotransmitters in the brain as tranquilizers and can also cause fatigue. Patients fighting the insomnia caused by dexamethasone may add to their post-dex fatigue by using certain sleeping medications.
¡ Anti-emetics are prescribed to control nausea and vomiting, but can also cause fatigue and asthenia through their effects on neurotransmitters.
¡ Antihistamines such as Benadryl® (diphenhydramine) are used to inhibit allergic responses and are frequently given to prevent drug reactions. They are also given to people to help them sleep, and thus can add to the general feeling of listlessness and fatigue.
Anxiety, stress, and depression
A cancer diagnosis is frequently accompanied by anxiety, stress, and depression. This is an understandable reaction when faced with a lifethreatening illness. Patients are anxious and depressed about having cancer and the unknown course ahead, about its financial impact, and about meeting expectations at work and in private life. Insomnia often accompanies feelings of depression and fatigue, aggravating the cycle of anxiety, stress, and fatigue.
It’s often difficult to know whether depression causes fatigue or vice versa, but it’s important to try to identify the primary problem. Talk to your doctor and seek a support system to help you manage your mental health. For some patients, the need for emotional support can be met within the community of family and friends; others seek membership in a support group with fellow myeloma patients, and seek professional help from a licensed family therapist, social worker, psychologist, or psychiatrist. There is no stigma attached to seeking help or to taking a medication for depression or anxiety that will help you feel and function better.
Poor nutrition
Fatigue can be the result of not eating or not absorbing enough calories, vitamins, minerals, and other nutrients. There are many reasons myeloma patients and cancer patients in general do not receive enough nutrition. Even when patients eat the same amount they did before diagnosis, they may lose weight because the body may not be able to absorb and use all available nutrients. Additionally, a growing tumor, an infection, a fever, and shortness of breath can all cause an increase in the amount of energy the body needs each day. Often, patients are dealing with treatments that cause nausea, diarrhea, constipation, or anorexia (appetite loss), and with emotional stress that dampens appetite.
The National Cancer Institute’s Eating Hints: Before, during, and after Cancer Treatment can be viewed and downloaded at cancer.gov/publications. This publication includes the helpful suggestions to maintain your weight and meet your nutritional needs.
Dehydration can also drain your energy. Make sure that you are drinking enough liquids to restore what may be lost with vomiting or diarrhea. All myeloma patients, but especially those with kidney dysfunction, must drink plenty of water to flush out their kidneys and reduce the side effects of medications.
Reduced activity
Contrary to widely held opinion, resting and napping is not the best remedy for cancer-related fatigue. Inactivity deepens fatigue. Experts
now recommend frequent light exercise to reduce fatigue and stress, build and maintain bone and muscle, and improve endurance. Walking just a short distance and trying to go a little further each day can help you gain strength. If bone pain makes it difficult to walk or do other exercises, swimming or treading water can be a non-stressful and very effective substitute. The resistance of the water helps to build muscle strength.
Sometimes practicing “mind over matter” can get you through a challenging day. At other times, doing something you enjoy can help you overcome the feelings of fatigue. To conserve energy, try alternating sedentary and more physically demanding activities and schedule activities at your times of peak energy.
Discuss all exercise plans with the doctor treating your myeloma and get clearance for anything you plan to do. Exercise should be tailored to your bone health and overall fitness.
Developing a plan with your healthcare team
Effective communication with your healthcare team is essential. If any changes have occurred that you think could be adding to your fatigue, discuss these with your doctors. Some factors that may not be obvious could be making your fatigue worse, and many are treatable. Your healthcare team can work with you and your care partner(s) to develop a plan for you.
Along with transfusions, medications, and dose and schedule adjustments that the doctor can help with, there are also a number of other things you can do to manage and cope with your fatigue, including the following:
¡ Exercise (walking, swimming, gentle yoga).
¡ Coping strategies (doing things you enjoy, seeing people you enjoy).
¡ Modification of activities (re-establishment of priorities, use of labor-saving devices, getting a good night’s sleep).
¡ Counseling.
If you are experiencing fatigue, your family members or other care partners can be great support. Feel free to talk with them about your fatigue and the impact it has on your life. Good communication is essential in your interactions with your medical team and with your support team.
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 a condition, and to answer scientific questions. Check the NCI database clinicaltrials.gov to learn if there is a study that might interest you, or contact the IMF InfoLine for assistance.
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.
Notes
INTERACTIVE RESOURCES AT A GLANCE
