Revlimid® (lenalidomide), an immunomodulatory drug (IMiD®), is the first oral medication that was developed for treatment of multiple myeloma. It is used in the newly diagnosed, maintenance therapy, and relapsed and/or refractory settings.
How Does It Work?
Revlimid has multiple actions, including both anti-cancer and anti-inflammatory activities. It induces immune responses, prevents inflammation, and enhances the activity of immune cells—specialized white blood cells known as T cells and natural killer (NK) cells. Revlimid also prevents the formation of new blood vessels that cancer cells depend upon for sustenance and growth.
How Is Revlimid Given?
Revlimid is given as capsules that are swallowed with water. The most common dosing used in myeloma is 25 mg given orally daily on days 1–21 and repeated every 28 days (days 22–28 are rest days). Doses are then modified based on side effects.
Patients with kidney disease may take Revlimid, but the dosage must be adjusted according to the level of remaining kidney function. Your doctor must follow the “Recommended Dosage for Patients with Renal [kidney] Impairment” included in the Revlimid prescribing information.
Possible Side Effects
Animal studies have shown that Revlimid can cause severe birth defects. To prevent severe birth defects from occurring as a result of pregnancy during treatment, the FDA required that a risk management program be established. The goals of the Revlimid Risk Evaluation and Mitigation Strategy (known as Revlimid REMS™) are as follows:
- To prevent the risk of embryo-fetal exposure to the drug.
- To inform prescribers, patients, and pharmacists on the serious risks and safe-use conditions for Revlimid.
Female patients of childbearing potential must undergo mandatory pregnancy testing and give informed consent before taking Revlimid. Female patients of childbearing potential and all male patients are also required to complete a monthly phone survey. Since most female myeloma patients are beyond the age of childbearing, they are enrolled in the REMS program by their physicians with a lower risk classification, and only have to do the phone survey once every six months. They will, however, have monthly counseling with the specialty pharmacy that dispenses their Revlimid.
Neutropenia (low levels of neutrophils)
Your neutrophil count will be monitored frequently while you are being treated, and your dose of Revlimid may be interrupted and/or lowered if your neutrophils are too low. For more information on neutropenia, visit Myelosuppression. In the maintenance therapy studies, severe neutropenia was reported in up to 59% of Revlimid-treated patients. Fever is the most common sign of neutropenia. If you have a fever, you need to contact your doctor immediately.
Thrombocytopenia (decreased platelet levels)
Patients taking Revlimid may experience thrombocytopenia, a lowered level of platelets in the blood. Platelets help blood to clot after an injury; fewer platelets can lead to bruising, bleeding, and slower healing. For more information on thrombocytopenia, visit Myelosuppression.
Venous thromboembolism (VTE)
VTE is a condition that includes both deep vein thrombosis (DVT) and pulmonary embolism (PE).
DVT is a blood clot (thrombus) in a deep vein of the lower extremities, usually occurring in the leg or thigh, very occasionally occurring in the neck or upper arm. A blood clot from a DVT can break loose (embolize) and travel to the heart or lungs. An embolus is very dangerous, and is potentially life-threatening.
PE is a condition that occurs when a blood clot in the vein breaks loose, travels through the bloodstream, and lodges in a lung, blocking blood flow.
Blood clots in the arteries, veins, and lungs occur more often in people who take take Revlimid than in the healthy population. Patients with multiple myeloma who take Revlimid in combination with dexamethasone increase the risk of developing blood clots. Heart attacks and strokes are also more frequent in people who take Revlimid with dexamethasone.
For more information on DVT, visit Heart and Lung Complications.
Other Side Effects
Diarrhea is defined as 3 or more loose stools per day, and severe diarrhea is defined as 7 or more loose stools per day requiring treatment with intravenous fluids or hospitalization. Diarrhea can be a troubling side effect of long-term Revlimid therapy that can severely affect quality of life and may lead to discontinuation of therapy if not well managed.
Revlimid modulates the immune system throughout the body to fight myeloma, including the immune system in the gut. The good news/bad news is that development of severe diarrhea among Revlimid-treated patients is associated with improved overall survival and is a sign of Revlimid’s immune control of the myeloma. For more information on diarrhea, see Gastrointestinal Problems.
Fatigue is commonly associated with Revlimid therapy. Even though fatigue is generally not severe, use caution if you are operating machinery, including automobiles.
The effects of fatigue may be minimized by
- A moderate level of activity
- A healthy diet and proper fluid intake
- A consistent sleeping schedule
Red blood cells contain hemoglobin, a protein that contains iron and transports oxygen from the lungs to the body’s organs and tissues. A low level of red blood cells results in low levels of oxygen in the body, which may cause shortness of breath and feelings of exhaustion. For more information, visit Multiple Myeloma and Anemia.
Rash is a serious concern. It is potentially dangerous, as a rash may be mild initially and then escalate in severity. Drug rashes vary in severity from mild redness with tiny bumps over a small area to peeling of the entire skin. Rashes may appear suddenly within minutes after a person takes a drug, or they may be delayed for hours or days.
If you develop a rash while taking Revlimid, report it to your doctor and/or nurse right away. Your doctor may interrupt or discontinue Revlimid if you have a moderate to severe skin rash.
Although it is rare, some Revlimid-related rashes can become very severe and life-threatening. Patients with a prior history of severe rash associated with Thalomid® treatment should not receive Revlimid.
Decreased appetite occurred in 23% of the newly diagnosed patients in the above-referenced clinical trial, only 3% of which was severe enough to cause weight loss or malnutrition.
Visit National Cancer Institute’s Eating Hints: Before, During, and After Cancer Treatment for helpful suggestions to maintain your weight and meet your nutritional needs.
Revlimid + dexamethasone
The major studies that were the basis of Revlimid’s approval in the relapse setting used a combination of Revlimid + dexamethasone. It is important to be aware that additional toxicities can occur with this combination versus Revlimid alone. Side effects that may occur with Revlimid + dexamethasone include muscle weakness, anxiety, agitation, cardiac arrhythmias, nausea, increased blood sugar, elevated liver enzymes, and constipation and/or diarrhea. The use of dexamethasone in myeloma is discussed in a separate IMF booklet, Understanding Dexamethasone and Other Steroids.
Revlimid prescribing information, including updated renal dosing guidelines
Celgene's Patient Support Coordinators assist patients and healthcare providers to navigate the challenges of reimbursement, provide information about co-pay assistance, and answer general questions about Revlimid.
Celgene has developed a new program called Fast Track for First Prescription™ to help eligible patients receive their first prescriptions for a Celgene product quickly and efficiently. Fast Track is an optional service of Celgene Patient Support that facilitates communication between doctors, patients, insurance providers, risk management programs, pharmacies, and co-pay foundations. To be eligible, patients must be receiving their first prescription of either Revlimid or Pomalyst, must have documented proof of insurance, and must be registered in a Celgene risk management program and have a valid authorization number. For more information on the program, call the IMF InfoLine at 1-800-452-2873.