Understanding Dexamethasone in the Treatment of 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 the steroid dexamethasone (also called “dex” for short), one of the most frequently used medications in the treatment of myeloma. Dexamethasone is the generic drug name of this medication, which is also marketed under multiple brand names.
How dexamethasone works
A steroid is a type of hormone. Steroidal hormones are produced by the body, and the synthetic analogues (equivalents) of some steroids can be manufactured in a laboratory. Dexamethasone is a synthetic steroid that has multiple effects and is used for many conditions, including myeloma. Dexamethasone is a synthetic adrenocortical steroid. In the body, adrenocortical steroids are produced naturally by the adrenal glands and are also known as glucocorticosteroids or corticosteroids. These compounds will be referred to as “steroids” throughout this booklet.
Adrenal glands produce both hormones and steroids. These steroids influence many actions of the body’s systems. They are involved in regulation of carbohydrates, proteins, and fats. They also inhibit inflammatory, allergic, and normal immune responses. Synthetic versions of steroids can imitate the actions of the naturally occurring compounds, or replace them in conditions that are associated with insufficient production of much-needed steroids that are normally produced by the adrenal glands.
Dexamethasone is available in many forms. To treat myeloma, dexamethasone can be given as either an oral tablet or as an injection, alone or in combination with other agents. Dexamethasone is used to treat a wide variety of medical conditions in addition to myeloma and other hematologic malignancies. Steroids are generally additive or synergistic with other treatments. Steroids as a component of treatment for myeloma may also help improve other conditions, such as the following:
¡ Endocrine disorders,
¡ Rheumatic or collagen disorders,
¡ Dermatologic diseases,
¡ Allergic states,
¡ Ophthalmic (eye) diseases,
¡ Gastrointestinal (GI) diseases,
¡ Respiratory diseases,
¡ Hematologic disorders,
¡ Other malignancies.
Dexamethasone and other steroids have many uses in the treatment of cancer. These steroids suppress certain actions of the immune system and also inhibit cytokines, which control inflammation. Dexamethasone decreases inflammation by stopping white blood cells (WBC), which normally fight infection, from traveling to areas of the body where there is swelling. Dexamethasone’s anti-inflammatory actions can stop the swelling around tumors and the resulting pain and other symptoms caused by
tumors pressing on nerve endings. Dexamethasone can also alter normal immune system responses and is therefore useful in the treatment of conditions that affect the immune system.
How dexamethasone is given
To treat myeloma, dexamethasone can be given as either an oral tablet or as an injection, alone or in combination with other agents. Dexamethasone can irritate the stomach; taking it with food can reduce the chances of this happening.
Steroid therapy cannot be stopped abruptly. Abrupt discontinuation can lead to withdrawal symptoms. If steroid therapy must be discontinued, it must be done gradually and under the supervision of the doctor treating your myeloma.
Dosages and scheduling of dexamethasone
Many factors are taken into consideration when your myeloma doctor determines your dose of dexamethasone and how it is administered. Ask your doctor about the optimal overall treatment strategy and about finding a dosing regimen that is well tolerated and appropriate for the treatment of your individual disease.
Dexamethasone has demonstrated activity in myeloma as a single agent but it is typically given in combination with one or more other agents, especially during induction therapy. Dexamethasone is a component of nearly all combination therapies, as it appears to increase or “boost” the ability of other agents to destroy myeloma cells, thereby improving response to treatment. However, dexamethasone is associated with many short-term and long-term side effects.
Dexamethasone 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.
Dexamethasone has been part of the vast majority of myeloma clinical trials over a period of many years. There have been numerous clinical trials of different combination therapies with low-dose dexamethasone in patients with newly diagnosed multiple myeloma (NDMM), as well as with relapsed and refractory disease.
Low-dose dexamethasone in combination with other agents has been well established as the standard of care in myeloma. Depending upon the age and fitness of the patient, dexamethasone is usually prescribed at a dose of 20 mg to 40 mg once-weekly. For patients who cannot tolerate
higher doses, dexamethasone has proven to be effective at doses as low as 4 mg once-weekly.
Secondary SWOG analysis
In September 2024, Blood published the secondary SWOG analysis, which concluded that dexamethasone dose intensity does affect the outcomes in patients with NDMM.
Dexamethasone is a key component of induction therapy for patients with NDMM despite common toxicities that include hyperglycemia and insomnia. In the randomized ECOG E4A03 clinical trial, 40 mg of dexamethasone once-weekly was associated with lower mortality than higher doses of dexamethasone. However, the performance of dexamethasone dose reductions below this threshold had not been fully characterized in NDMM patients in terms of progression-free survival (PFS) and overall survival (OS).
The secondary pooled analysis of the SWOG clinical trials S0777 and S1211 compared three combination therapies: the immunomodulatory agent Revlimid® (lenalidomide) + dexamethasone [Rd], the proteasome inhibitor Velcade® (bortezomib) + Rd [VRd], and the monoclonal antibody Empliciti® (elotuzumab) + VRd [Elo-VRd]. Planned dexamethasone intensity was from 40 mg to 60 mg once-weekly in all study arms. Patients were categorized into full-dose dexamethasone [FD-DEX] maintained throughout induction therapy, lowered-dose dexamethasone [LD-DEX], or discontinuation.
Of the 541 evaluated patients, the LD-DEX group was comprised of 373 patients (69%). There was no difference in PFS or OS between the FD-DEX and LD-DEX groups, which were balanced in terms of age, disease stage, and performance status. Predictors of PFS and OS were treatment arm, age ≥70, and thrombocytopenia. FD-DEX did not significantly improve either outcome.
The study suggests that dexamethasone dose reductions below 40 mg once-weekly are common in myeloma, even within clinical trials, and do not negatively impact PFS or OS. Given dexamethasone’s toxicities and unclear benefit in the era of modern treatment regimens, lowered-dose dexamethasone during induction therapy of patients with NDMM warrants further study.
Rd regimen vs. DR regimen
In December 2022, at the annual meeting of the American Society of Hematology (ASH), the efficacy and safety analysis of the IFM2017-03 phase III clinical trial became a point of interest for its limited use of dexamethasone in frail or elderly patients with newly diagnosed myeloma. The Rd regimen was compared to a combination of Darzalex® (daratumumab) + Revlimid [DR],
in which patients received only 2 months of dexamethasone. The DR regimen had deeper responses, with overall response rate (ORR) of 96% and complete response (CR) rate of 37%. The Rd regimen had ORR of 85% and CR of 10%.
Rd-R regimen vs. continuous Rd
In 2021, the journal Blood published the results of a clinical trial designed specifically for treatment of older and less fit patients with myeloma, a group usually excluded from clinical trials. Newly diagnosed patients who were 65–80 years old and who were “intermediate-fit” on the International Myeloma Working Group (IMWG) frailty score were randomized to receive 9 months of Rd followed by maintenance therapy of Revlimid (without dexamethasone) at 10 mg per day [Rd-R] or to a study arm that received continuous Rd.
Side effects were mainly related to dexamethasone and were more frequent with continuous Rd. After 9 cycles of Rd, switching to reduced-dose Revlimid maintenance therapy without dexamethasone was feasible, with similar outcomes to standard continuous Rd.
ECOG E4A03 clinical trial
In 2010, the results of the large ECOG E4A03 clinical trial were published in Lancet Oncology. Prior to this study, the standard of care in myeloma included 40 mg of dexamethasone administered 4 days per week (“highdose”). The E4A03 study is the legacy of Michael Katz, who was diagnosed with myeloma in 1990 and later became a myeloma support group leader and a member of the IMF Board of Directors.
Michael lost his battle with myeloma 25 years after diagnosis, but it was his perseverance and insight that led to the evaluation of the Rd frontline therapy of Revlimid with either high-dose or low-dose dexamethasone. The 1 day per week (“low-dose”) schedule of 40 mg dexamethasone demonstrated better survival at 1 year, with significantly fewer side effects than the 4 days per week schedule.
Possible side effects of dexamethasone
Dexamethasone can cause side effects. Few patients experience all of the possible side effects described in this section. Some patients do not experience any side effects at all while taking dexamethasone. Ask your doctor how to best prevent, minimize, or treat possible side effects.
You and your doctor can take precautionary measures in order to reduce or avoid side effects. The most important precautions are described in this booklet, and your doctor can provide greater detail about these and other possible side effects, and make recommendations about their management.
The longer you take a steroid, and the higher the dose, the greater your chances of experiencing side effects, but most side effects will go away
when treatment is completed. Alert your doctor if you are experiencing side effects or if you notice changes in your health.
Do not stop taking any of your medications or reduce your doses on your own. Discuss your concerns with the doctor who is treating your myeloma.
Infections
Dexamethasone is a component of nearly all combination therapies used in myeloma. Any drug that suppresses normal immune responses can make you susceptible to infections, and patients who are taking dexamethasone or other steroids have an increased risk of all types of infections (bacterial, viral, or fungal).
Steroids block white blood cells from reaching sites of infection, and may cause existing infections to get worse or allow new infections to begin. Steroids can mask signs that an infection is present and may also decrease your immune system’s ability to fight the start of a new infection.
Prevention and treatment of infections
Generally, steroids should not be administered to a patient who has a known infection. Nevertheless, there are some situations in which steroids may be important or necessary during the time that an active infection is being treated appropriately. For example, steroids are useful in the treatment of septic shock, an infection that involves the whole body, and in treating any serious infection that causes a major inflammatory response and/or tissue destruction.
You must tell your doctor as soon as possible if you have been exposed to any infectious illnesses, or if you have any signs or symptoms of an infection. In addition, your doctor must know your entire vaccination history to date. Also, make sure to wash your hands frequently, especially after being in public places.
Cardiac conditions and fluid retention
Use of dexamethasone and other steroids can cause increases in blood pressure, salt and water retention, and potassium and calcium excretion. These changes are more likely to occur when steroids are taken in large doses. Salt retention may lead to edema or swelling. You may notice that your ankles and feet are swollen. Fluid retention and loss of potassium can be a problem for patients who have cardiac conditions, especially congestive heart failure and hypertension.
Prevention and treatment of cardiac conditions and fluid retention
Discuss with your doctor if changes to your diet may be needed, such as restricting your salt intake or replacing the potassium and calcium that you may be losing. Consult with your healthcare team to make sure that you are eating the right foods.
Dermatologic effects
Patients taking dexamethasone or other steroids may notice that it takes longer than usual for wounds to heal. Patients may develop acne and rashes while taking dexamethasone. Increased sweating is seen in some patients during steroid therapy.
Prevention and treatment of dermatologic conditions
Proper hygiene is important. If your dermis (skin) is injured, administer first aid and contact your healthcare team.
Endocrine effects
Steroids, including dexamethasone, may interfere with the way patients metabolize carbohydrates and can cause blood glucose levels to rise. This is especially important in patients who have diabetes. Patients with diabetes can take steroids, but additional treatment, including insulin therapy, may be needed to control blood sugar levels. Steroids can also cause menstrual irregularities.
Prevention and treatment of endocrine effects
Patients with diabetes may need to monitor their blood glucose levels more frequently. These patients may need to adjust the doses of their insulin or diabetes medications. This decision needs to be made by healthcare professionals and not by patients themselves. If you have diabetes, tell the doctor who is treating your diabetes that you have been prescribed dexamethasone.
Females of childbearing potential, especially those experiencing menstrual irregularities, should take added precautions not to become pregnant while taking dexamethasone, and should speak with their doctor about the potential effects of steroids on the developing child.
Gastrointestinal (GI) effects
Steroids can have various effects on your GI tract, such as increasing the risk of GI perforations (holes). Therefore, patients who have peptic ulcers, diverticulitis, and ulcerative colitis should use corticosteroids cautiously to minimize the risk of perforation. For these reasons, many physicians automatically recommend antacid therapy of some type for patients taking steroids. Other possible GI side effects seen with dexamethasone therapy are increased or decreased appetite, stomach bloating, nausea, vomiting, hiccups, and heartburn.
Prevention and treatment of gastrointestinal effects
Tell your doctor if you experience any GI side effects while taking dexamethasone and ask for advice on how to manage or avoid these events. To avoid or minimize GI irritation, dexamethasone should be
taken with food or after meals. Alcoholic beverages, which may also irritate the stomach, should be avoided while taking dexamethasone. Limiting intake of caffeine-containing foods and drinks (e.g., colas, coffee, tea, and chocolate) may also help. Eating small, frequent meals may decrease nausea. Antacids taken between meals may also be helpful, but should not be taken unless approved by your healthcare team. Treatment for persistent hiccups may require such prescription drugs as baclofen, chlorpromazine, or promethazine.
Musculoskeletal effects
Because steroids decrease calcium absorption and increase its excretion, they affect bones. These effects can lead to pain and osteoporosis in adults. Patients with myeloma who are already subject to severe bone loss and bone pain must be watched carefully and given appropriate supportive care to prevent further bone damage. Patients taking steroids may also experience muscle pains because they may be losing potassium.
Prevention and treatment of musculoskeletal effects
Consult with your doctor before taking any supplements or changing your diet. Do not take any supplements or make changes to your diet on your own. Your doctor may recommend supplements or that you increase your intake of calcium and potassium. The best dietary sources of calcium are dairy products, dark-green leafy vegetables, peas and beans, canned fish such as sardines and salmon, and calcium-fortified juices and cereals. Potassium is available in many fruits and vegetables, leafy greens, beans, nuts, dairy foods, and starchy vegetables.
Many patients with myeloma receive bisphosphonate therapy as treatment for myeloma-related bone disease. Bisphosphonate therapy also combats the negative effects of steroids on bone strength and density.
Ophthalmologic effects
Prolonged steroid treatment may produce elevated intraocular pressure that could lead to glaucoma, optic nerve damage, eye infections, and cataracts. Cataracts occur commonly in older age and usually take years to develop to the point where surgery is indicated. Steroids can speed up this process. With ongoing steroid treatment, it is not uncommon for myeloma patients to develop mature cataracts requiring surgery. This involves removal of the cataract and implantation of a new lens in the eye, which usually allows for enhanced vision.
Prevention and treatment of ophthalmologic effects
Have your eyes checked regularly. Any change in vision should be reported immediately to your healthcare team.
Psychiatric and neurologic effects
Steroids can also cause irritability, mood swings, personality changes, insomnia, and severe depression. Emotional instability or psychotic tendencies are aggravated and may become worse during steroid therapy. Patients also have reported experiencing headaches and dizziness.
Prevention and treatment of psychiatric and neurologic effects
If you are having problems sleeping, ask your healthcare team if you can adjust the time you take dexamethasone so it doesn’t interfere with your sleep during the night. Taking steroids before going to bed can be very effective in allowing sleep during the night, with increased activity delayed until morning. However, regular sleep medications can be helpful or necessary for some patients.
Do not hesitate to contact your doctor if you are experiencing any mood or personality effects. Your doctor may need to reduce or stop your steroid therapy temporarily or permanently. Do not stop steroid therapy on your own without consulting your doctor.
Family members should be advised that you may be more irritable and difficult to live with when you are receiving steroid therapy. Counseling may be a good option at this time, both for the patient and for the care partners. The stresses and pressures of a cancer diagnosis added to life’s other challenges may lead to psychological overload not only for a patient who is receiving steroids, but for the patient’s family members as well. A consultation with a family counselor can be most helpful.
Allergic reactions
Allergic and hypersensitivity reactions to steroids are possible in patients who are susceptible or have had allergic reactions to other drugs. Allergic reactions can include difficulty breathing, closing of the throat, swelling of the lips and tongue, and hives. Such allergic reactions to steroids are exceedingly rare.
Prevention and treatment of allergic reactions
Special precaution should be used before administering dexamethasone or any other corticosteroid to patients who have histories of any type of allergic reactions to medications. Be sure to alert your healthcare team if you have a history of allergic responses when given any medication.
General effects
Some patients may experience coughing or hoarseness. Resting the voice can help with this condition.
Use of steroids, including dexamethasone, can cause weight gain.
Prevention and treatment of weight gain
Some weight gain is to be expected during steroid therapy. Dexamethasone has a tendency to increase patients’ appetites. Patients may need to control their caloric intake. Reduced carbohydrate intake is especially helpful during steroid therapy. Let your healthcare team know immediately if there is a sudden, large weight gain (more than 5 pounds over a day or two).
Other corticosteroids used to treat myeloma
In addition to dexamethasone, other corticosteroids are used to treat patients with myeloma. Because these drugs all belong to the glucocorticosteroids class of drugs, they act very similarly and can be used to treat many of the same medical conditions. They behave the same way chemically in the body to treat diseases. Because they are so similar in their mechanisms of action, many of the side effects and associated precautions are the same. Some of the steroids may be better tolerated than others, depending on the patient and the drug.
The uses, side effects, precautions, and considerations described previously for dexamethasone are relevant for the entire class of corticosteroids and thus pertain to prednisone, prednisolone, and methylprednisolone. Prednisolone is a metabolite of prednisone. Methylprednisolone, although structurally similar, may be less toxic and appears to be associated with less sodium and fluid retention than prednisolone.
Ask your doctor if any steroid other than dexamethasone might be more effective or more appropriate in your particular case.
Possible drug interactions
Interactions are possible with dexamethasone or other steroids and other medications. Patients with myeloma typically need to take a number of medications to treat the disease as well as other medical conditions that also may be present. Chances of drug interactions increase with multiple medications. Below is a partial list of medications or classes of medications that may interact with dexamethasone or other steroids. These interactions may increase or decrease the actions of any of the drugs. It is very important to tell your doctor about all prescription and over-the-counter (OTC) medications, as well as any herbal preparations, vitamins, or minerals that you are taking.
¡ Amphotericin B and diuretics that affect potassium levels (such as amiloride, spironolactone, and triamterene).
¡ Antibiotics (such as erythromycin, clarithromycin, rifampicin, and azithromycin).
¡ Anticoagulant medications (such as warfarin and aspirin).
¡ Barbiturates (such as amobarbital, butalbital, pentobarbital, and secobarbital).
¡ Diabetes medications (e.g., insulin, glibenclamide, and metformin).
¡ Cyclosporine.
¡ Digitalis.
¡ Ephedrine, which is most commonly found in weight-loss products.
¡ Estrogen-containing medications, including oral contraceptives and hormone-replacement therapy products.
¡ Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, ibuprofen, indomethacin, and naproxen.
¡ Phenytoin.
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.
INTERACTIVE RESOURCES AT A GLANCE
Dr. Joseph Mikhael
IMF Chief Medical Officer
