Understanding Dexamethasone in the Treatment of Myeloma
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What you will learn from this booklet
This booklet discusses the steroid dexamethasone (also called “dex” for short). Dex is available as a generic drug and it is also marketed under several brand names. This booklet explains how dex works, how it is given, possible drug interactions, potential side effects and how they can be prevented or minimized, and more.
Who can be treated with dexamethasone
Dex is a part of many combination therapies used in myeloma throughout the disease course. Steroids are generally used in combination with other drugs to produce a combined benefit.
In addition to dex, other steroids used to treat patients with myeloma include prednisone, prednisolone, and methylprednisolone. Because these steroids all belong to the same drug class, they behave similarly in the body and can be used to treat many of the same medical conditions.
Different steroids have many of the same side effects on the body and they are used to treat many medical conditions. This includes myeloma, other types of blood disorders, and conditions such as:
¡ Endocrine disorders,
¡ Rheumatic or collagen disorders,
¡ Dermatologic (skin) diseases,
¡ Ophthalmic (eye) diseases,
¡ Gastrointestinal (GI) diseases,
¡ Respiratory diseases, and
¡ Allergies.
How dexamethasone works
Dex is a type of hormone. In the human body, adrenal glands produce both steroids and hormones. Steroids can suppress certain actions of the immune system. Steroids influence the regulation of carbohydrates, proteins, and fats. Steroids also inhibit cytokines that control inflammation. Steroids can prevent or decrease allergic and other immune responses.
Synthetic steroids like dex imitate the functions of naturally occurring steroids. Dex can replace or supplement the steroids produced naturally by the adrenal glands. Dex can decrease inflammation by stopping white blood cells (WBC) from traveling to areas of the body where there is swelling. Dex can stop the swelling around tumors and the pain caused by tumors pressing on nerve endings.
Benefits of dexamethasone
Dex is useful in the treatment of conditions that affect the immune system, such as myeloma. Dex has been proven to be effective in myeloma even when used alone as a single agent (monotherapy). But dex is typically given in combination with other drugs as it improves their ability to destroy myeloma cells. In brief, dex is helpful in several myeloma-related settings:
¡ Dex kills myeloma cells directly.
¡ Dex enhances the benefits of other anti-myeloma drugs.
¡ Dex is helpful during treatment with bispecific antibodies or CAR T-cell therapies.
¡ Dex is used to help patients reduce their nausea.
¡ Dex is an effective defensive measure against allergic reactions, nausea, and infusion-related reaction (IRR).
¡ Dex can quickly reduce pain and swelling, including bone pain, pressure on nerves, and compression of the spinal cord.
How dexamethasone is given
Dex can be given by mouth as an oral tablet or as an intravenous (IV) infusion into a vein. If you are taking all your medications by mouth, your dex will be given to you in tablet form. If you are receiving some of your medications through an IV, your dex may be given to you by IV or you may still take it as a tablet.
IMPORTANT: Steroid therapy cannot be stopped abruptly. This can lead to withdrawal symptoms. If steroid therapy must be discontinued, your myeloma doctor must supervise a gradual tapering of this medication.
Dose and schedule of dexamethasone
In April 2026, the Journal of Clinical Oncology (JCO), the official journal of the American Society of Clinical Oncology (ASCO), published the review article “Past, Present, and Future of Dexamethasone in Multiple Myeloma and AL Amyloidosis,” which covers the use of dex in myeloma since the 1950s. You can read the full text at pubmed.ncbi.nlm.nih.gov.
Dexamethasone at 40 mg vs. 160 mg
Originally, dex was given to patients 4 days per week at 40 milligrams (mg) – a total of 160 mg weekly, a very high dose with numerous side effects! Then the ECOG E4A03 clinical trial compared combining Revlimid® (lenalidomide) + high-dose dex vs. Revlimid + lower-dose dex in patients with newly diagnosed multiple myeloma (NDMM). A clinical trial is a medical research study with people who volunteer to test scientific approaches
and answer scientific questions. A clinical trial is launched only after laboratory studies have shown the potential of a treatment or procedure to be more effective and/or less harmful than previous methods.
The ECOG E4A03 study’s conclusion was published in the journal Lancet Oncology in 2010. The lower-dose dex regimen of 40 mg given once-weekly was proven to be superior, with higher response rates and far fewer side effects. Importantly, the ECOG E4A03 study showed increased mortality with high-dose dex. The overall survival (OS) was 96% in the low-dose dex group compared to 87% in the high-dose group. The improvement in survival and toxicity was so decisive that the Data Monitoring Committee stopped the trial early to switch all the patients in the high-dose dex study group to low-dose dex.
In a clinical trial, OS represents the amount of time from diagnosis or start of treatment until death from any cause. OS used to be the standard for assessing if a treatment extends a patient’s life. As myeloma therapies become more effective and OS duration is increased, clinical trials are using faster endpoints to validate outcomes.
At that time, the 2-drug Rd combination therapy was considered a standard of care for NDMM. Since then, dex doses of 40 mg once weekly have been given to myeloma patients – and often continued for months or years. However, evidence continued to show dose-dependent side effects, such as cataracts and infections and more. These side effects can have a significant negative effect on a patient’s quality of life.
Dexamethasone at 20 mg to 40 mg once-weekly
Authors of the JCO article state that dex at a dose of 20 mg to 40 mg onceweekly is still associated with dose-related side effects. In patients with RRMM, clinical trials have shown that indefinite once-weekly doses of dex cause more side effects.
Published in 2021, a study comparing Sarclisa® (isatuximab) + dexamethasone [Isa-d] vs. Sarclisa alone showed that patients in the dex group experienced 25% insomnia vs. 2% in the Sarclisa alone group.
The GEM-CLARIDEX clinical trial of Rd with or without the antibiotic clarithromycin in NDMM saw an increase in infectious deaths in the clarithromycin arm. This was attributed to clarithromycin-related CYP3A4 inhibition that led to increased dex exposure above the dose of 20 mg once-weekly given to most patients.
The negative impacts of chronic steroid use on bone health, glycemic control, and peptic ulcers have not been studied in myeloma. However, several reviews – in healthy adults and people with autoimmune conditions – have identified negative associations even with low-dose steroids.
Split dosing of dexamethasone
There is no consensus among myeloma specialists about once-weekly dosing vs. split dosing. Which is better, taking split doses of 20 mg of dex for 2 consecutive days or taking 40 mg at once? If you are at higher risk of side effects such as dizziness or hyperglycemia, ask your doctor if split dosing should be considered in your particular case of myeloma.
In one study, patients receiving twice-per-week Velcade® (bortezomib) received split-dosing of dex with each of their Velcade doses. Patients receiving their dex twice per week had less numbness, tingling, burning, and/or pain caused by nerve damage. This is called neuropathy and 46% of patients on split-dosing developed it. Of the patients receiving once-weekly dosing, 64% developed neuropathy.
However, this split-dosing schedule may not be applicable to patients receiving Velcade once-weekly, which is a schedule used far more frequently with Velcade.
Dexamethasone with/without transplant
All modern phase III clinical trials with NDMM patients who are eligible for an autologous stem cell transplant (ASCT) have used weekly dex doses of 40 mg and higher. Clinical trials with NDMM patients who are not eligible for ASCT have used average total dex doses below 60 mg weekly; half of these studies used individualized dosing strategies, such as 20 mg once-weekly for patients age 75 or older.
A pooled analysis of two studies assessed more than 500 patients who received dex at 40 mg to 60 mg once-weekly with Rd, Velcade + Rd [ VRd], or Empliciti® (elotuzumab) + VRd [Elo-VRd]. Only 31% of patients stayed on their dex doses for the 24-week period of frontline therapy, the initial treatment given to a patient with NDMM. There were no significant differences between the two groups in OS or progression-free survival (PFS). PFS is 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.
Published in 2021, the MAIA phase III clinical trial studied a group of patients who received Darzalex® (daratumumab) + Rd [DRd], with dex dosing at 20 mg to 40 mg once-weekly until progression. Published in 2024, the phase III IFM2017-03 clinical trial of older and more frail patients compared Rd vs. a modified version of the DRd regimen, with the DRd patients receiving only 8 weeks of dex at 20 mg once-weekly.
The total exposure to dex in the IFM2017-03 study was less than 5% of the total exposure to dex in the MAIA study. The median PFS was 53.4 months
in IFM 2017-03 vs. 22.5 months in MAIA. The IFM2017-03 dosing of 8 weeks of dex at 20 mg once-weekly is an evidence-based standard-of-care for ASCT-ineligible patients.
Published in 2025, the REST phase II single-arm clinical trial of Sarclisa + VRd [Isa-VRd] studied frontline therapy in ASCT-ineligible patients. Several studies of Isa-VRd have been conducted in ASCT-ineligible patients but the REST study patients included 31% of patients who were 80 years and older, and 45% were considered frail. Dex at 20 mg onceweekly was stopped after 8 weeks. Quality of life was preserved with this approach. The overall response rate (ORR) was 100% and MRD negativity was 41%. This shows that more exposure to dex is largely unnecessary in NDMM patients.
Dexamethasone after frontline therapy
Post-induction therapy is given after ASCT as maintenance therapy for transplant-eligible patients. It is also given to transplant-ineligible patients as their treatment is reduced. Post-induction therapy can continue for many years, in which case the side effects from the total amount of dex received by the patient most likely outweigh the benefits of dex.
In 2021, a study published in the journal Blood compared continuous Rd with 20 mg dex once-weekly in elderly, intermediate-fit patients with NDMM vs. dose/schedule-adjusted Rd with dex that was stopped after 9 months and maintenance with Revlimid alone at 10 mg per day [Rd-R]. PFS was comparable between the two groups of patients, but the Rd-R group met the study’s primary endpoint for superior event-free survival. At 3 years, OS was 74% in the Rd-R group vs. 63% in the Rd group, demonstrating that dex should not be routinely used in maintenance therapy.
Dexamethasone in the modern era
Given the many significant advances in the treatment of myeloma, many myeloma specialists would agree that doses of dex are generally still too high for most patients. The National Comprehensive Cancer Network (NCCN) guidelines recommend using the lowest possible effective dose of steroid for older adults. But the NCCN has made no recommendations on how to determine the dose.
Data from several clinical trials support stopping dex after 1 or 2 cycles in patients who are older and frailer. In addition, data suggest that patients who are given dex indefinitely may experience reduced efficacy of therapies if their myeloma progresses. Dex in supportive care is often sufficient at lower doses of 4 mg to 8 mg given as needed.
All steroids can have short-term and long-term side effects. More studies are needed to better understand the use of dex in myeloma. The dose of dex depends on the age and fitness or frailty of the myeloma patient. Ideally, you tolerate your dose of dex well. But don’t wait to ask your doctor if your dex dosing and schedule should be personalized.
Your myeloma doctor takes many factors into account when advising you about your overall treatment strategy, including your dose and schedule of dex. Shared decision-making takes into account your current and future preferences. For more information, read the IMF’s publication Myeloma Treatment Discussion Tool.
Possible side effects of dexamethasone
Dex can cause side effects. Few patients experience all of the possible side effects. Some patients do not experience any side effects at all.
Alert your doctor if you experience any side effects or if you notice changes in your health. Do not skip or stop taking your medication. Do not reduce your doses on your own.
The longer you take dex and the higher your dose, the greater your chances of having side effects. Most side effects will go away when treatment is completed. Ask your doctor how you can avoid or reduce side effects from dex, or manage the side effects if they occur.
The most important side effects are described in this booklet.
Infections
Any drug that suppresses your immune system increases your risk of infections. Steroids can make you vulnerable to bacterial, viral, or fungal infection. Steroids can cause existing infections to get worse. Generally, steroids should not be given to a patient who has an infection. But steroids may be necessary to treat serious infections that cause major inflammation or tissue destruction, such as septic shock (an infection that involves the whole body).
Alert your doctor as soon as possible if you have been exposed to an infectious illness. Your doctor must know your entire vaccination history. Also, make sure to wash your hands frequently, especially after being in public places.
Steroids can hide the signs of infection. But a blood test can detect that your immune system is fighting an infection if it shows abnormal white blood cell counts, elevated inflammatory markers, or microscopic germs in your bloodstream.
Heart conditions and high blood pressure
Steroids can raise blood pressure, make the body hold more salt and water, and cause it to lose potassium and calcium. This can cause swelling (edema), especially in the feet and ankles.
Extra fluid and low potassium can be serious for people who have high blood pressure or congestive heart failure. Your doctor may direct you to modify your diet, restrict salt intake, or add foods higher in potassium and calcium.
The steroid methylprednisolone tends to cause less fluid retention. Ask your doctor if it may be an appropriate option for you.
Skin side effects
Steroids can cause increased sweating, acne, rashes, and bruising. It may take longer than usual for wounds to heal. Proper hygiene is especially important when taking steroids. If your skin is injured, administer first aid and contact your doctor.
Endocrine side effects
Steroids can interfere with how you metabolize carbohydrates and can cause blood glucose levels to rise. Patients with diabetes can take steroids but may need to monitor their blood glucose levels more frequently. Your doctor will decide if additional medication to control blood sugar levels is needed; do not adjust your medication on your own.
Steroids can also cause menstrual irregularities. Women of reproductive potential should take added precautions not to become pregnant while taking dex. If you are pregnant, ask your doctor about the potential effects of your medications on the developing child.
Gastrointestinal (GI) effects
Steroids can irritate the stomach. Dex should be taken with food or after meals to avoid or minimize bloating, nausea, vomiting, hiccups, and heartburn.
Steroids can increase the risk of GI holes (perforations). Patients with peptic ulcers, diverticulitis, and ulcerative colitis may be prescribed antacid therapy to take between meals.
To decrease nausea, eat small and frequent meals. Medication may be prescribed to treat constant hiccups. Avoid alcoholic beverages and limit caffeine.
Steroids can decrease or increase appetite. Increased caloric intake can cause weight gain. Reducing carbohydrate intake is especially helpful during steroid therapy. Alert the doctor if you gain of 5 pounds or more over only a day or two.
Musculoskeletal side effects
Steroids affect bones because they decrease calcium absorption and increase calcium excretion. This can lead to pain and osteoporosis. Patients with myeloma who already have bone loss and bone pain must be monitored carefully by their doctors. Appropriate care can prevent further bone damage.
Steroids can cause muscle weakness and muscle pains due to the loss of potassium. Do not take any supplements or change your diet without consulting your doctor. Potassium is available in many fruits and vegetables, leafy greens, beans, nuts, dairy foods, and starchy vegetables.
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.
Many patients with myeloma receive bisphosphonate therapy as treatment for myeloma-related bone disease. Bisphosphonate therapy also reduces the negative effects of steroids on bone strength and density. For more information, read the IMF’s publication Understanding Treatment of Myeloma Bone Disease.
Eye (ophthalmologic) side effects
Prolonged steroid treatment may raise intraocular pressure that could lead to glaucoma, optic nerve damage, cataracts, and eye infections.
Cataracts are common in older age and usually take years to develop. Steroids can speed up this process. Cataract surgery involves replacing a cataract with a new lens to improve vision. Be sure to have your eyes checked regularly. Report any change in vision immediately to your doctor.
Allergic reactions
Allergic hypersensitivity reactions to steroids are rare but possible, and more likely in patients who have been allergic to other drugs. Alert your doctor if you have a history of allergic responses to any medication.
Symptoms of allergic reactions include difficulty breathing, closing of the throat, swelling of the lips and tongue, and skin hives.
Psychiatric and neurologic effects
Steroids can cause irritability, mood swings, personality changes, insomnia, and depression. Patients taking dex may have cognitive and behavioral changes, which can affect the patient and/or those around them.
Psychotic tendencies may become worse during steroid therapy. Patients have also reported headaches and dizziness. Your doctor may need to reduce or stop your steroid therapy temporarily or permanently; do not make any changes on your own.
If you have insomnia, ask your doctor if taking dex earlier in the day can lower the chances of dex interfering with your sleep. However, taking dex before going to bed can be very effective in helping you sleep through the night, with sleep medication prescribed if needed.
Message to care partners
If your loved one is receiving steroid therapy, they may become more short-tempered. The stresses and pressures of a myeloma diagnosis added to life’s other challenges may feel overwhelming for the patient. Counseling may be helpful to both the patient and to the care partners. Visit carepartners.myeloma.org for available resources.
Possible drug interactions
It is possible for steroids to interact and interfere with other medications. Most myeloma therapies are made up of several medications. Some myeloma patients have other medical conditions that also require treatment. The more medications you take, the greater the chances of drug interactions. Below is a partial list of prescription and over-the-counter medications that may interact with steroids:
¡ Amphotericin B,
¡ Antibiotics,
¡ Anticoagulants,
¡ Barbiturates,
¡ Cyclosporine,
¡ Diabetes medications,
¡ Digitalis,
¡ Diuretics,
¡ Ephedrine,
¡ Phenytoin,
¡ Nonsteroidal anti-inflammatory drugs (NSAIDs),
¡ Estrogen-containing medications (including oral contraceptives and hormone-replacement therapy products).
In closing
This booklet is not meant to replace the advice of your doctors and nurses who are best able to answer questions about your specific healthcare management plan. The IMF provides educational information that will guide you in your conversations with your healthcare team.
To help ensure a good quality of life through effective treatment, you must have an active role in your own medical care. Please visit myeloma.org and join the IMF Myeloma Knowledge Platform at myprofile.myeloma.org.
Click on the links included in this booklet for quick access to a variety of resources. Sign up at subscribe.myeloma.org for our quarterly journal Myeloma Today and weekly e-newsletter Myeloma Minute, as well as alerts about IMF news, events, and actions.
Notes
Founded in 1990, the International Myeloma Foundation (IMF) is the world’s leading organization dedicated to multiple myeloma. The IMF is steadfast in its mission: Accelerating the prevention and cure of myeloma and improving the quality of life for patients and families.
The IMF serves people impacted by myeloma at every stage of the disease by combining world-class research, trusted education, global advocacy, and direct support. A cornerstone of this work is the International Myeloma Working Group® (IMWG) – a network of more than 300 internationally renowned researchers and clinicians who establish the guidelines that shape how myeloma is diagnosed, treated, and managed across the globe.
Through its global network of support groups, educational programs, its 24/7 generative-AI myeloma assistant Myelo® , its InfoLine staff, and its advocacy for greater healthcare access, the IMF helps people living with myeloma and their care partners navigate diagnosis, treatment, and survivorship. At the same time, the IMF ensures scientific advances translate into better care and outcomes.