Thalomid (thalidomide) for Treatment in Myeloma

THALOMID® is an oral immunomodulatory drug, an agent that can modify or regulate the immune system. It has both anti-inflammatory and anti-cancer activities. Thalidomide was first used to treat multiple myeloma in 1997. It was officially approved for use in treating myeloma in combination with the steroid dexamethasone in 2006. The first effective new drug to treat MM in decades, Thalomid launched a new era of "novel therapies." It gave rise to a next generation of immune modulators with increased efficacy and reduced side effects, or the drugs Revlimid® (lenalidomide) and Pomalyst® (pomalidomide). 

Currently, thalidomide is used infrequently in the U.S. Yet, it is still sometimes used during late stage of disease, in cases of renal failure, or when the patient has low blood counts. Thalidomide is sometimes used in induction therapy and consolidation therapy. Thalidomide continues to be used more often abroad. Because Revlimid can cause low blood counts. thalidomide may be an alternative therapy. Thalidomide has a more minor impact on the bone marrow’s ability to make new blood cells. Moreover, thalidomide may be a more affordable option for patients whose insurers cover the cost of Revlimid inadequately or not at all. 

How Does Thalomid Work?

Thalidomide is an oral, small-molecule immunomodulatory agent that has both anti-inflammatory and anti-cancer activities. Immunomodulatory agents can modify, enhance, or suppress the functioning of the immune system. 

Immunomodulatory agents inhibit inflammation by altering the levels of growth factors called cytokines and interleukins. Immunomodulatory agents kill cancer cells by enhancing the activation of specialized T cells (T lymphocytes) called natural killer (NK) cells and by inhibiting the growth of blood vessels upon which cancer cells depend for sustenance and growth.  

Response to thalidomide therapy takes time. In myeloma, improvement is typically seen after about 3 months of treatment. Yet, improvement has also occurred as early as 2 weeks and as late as 8 months after initiating treatment. Once a response is achieved, your doctor will determine if ongoing maintenance therapy is appropriate. 

Thalidomide is not chemotherapy. Immunomodulatory agents work very differently from chemotherapy agents. Chemotherapy agents kill cells that are dividing rapidly, including cancer cells as well as normal cells like hair cells and the cells of the mucosa lining the mouth and digestive tract.

How Is Thalidomide Taken? 

Thalidomide is taken by mouth. Since you do not need to be at the doctor’s office or in a clinic or hospital to receive thalidomide, it is your responsibility to take thalidomide as directed by your doctor.  

Make sure to read and understand the information in the IMF publication Understanding Thalidodmide Therapy in Myeloma and in any other materials your doctor provides. Before you begin taking thalidomide, we recommend that you also read a related IMF tip card, Adherence to Oral Cancer Therapy. 

What Is the Dose and Schedule of Thalidomide? 

Your dose of thalidomide will be determined by your doctor based on the following: 

• whether thalidomide is being given alone or in combination with other drugs 
• how thalidomide is tolerated by your body 

To ensure that the most effective dose is given as safely as possible, your dose may be gradually increased over time. The dose may be modified only under the direction of your doctor. 

Over the years, with the data gathered from clinical trials, doctors have learned to tailor the dose and schedule of thalidomide, dexamethasone [Td] combination therapy to improve patients’ quality of life. When quality of life improves, patients can adhere better to a treatment protocol, and in turn respond better to the treatment. A study of low-dose versus high-dose thalidomide for advanced myeloma was published in 2012 in the European Journal of Hematology by Intergroupe Francophone du Myélome (IFM), the French myeloma research group. The study concluded that “low-dose thalidomide 100 mg/day has significant activity in advanced myeloma with an improved safety profile.”  

Thalidomide is rarely prescribed at doses greater than 100 mg/day. Dexamethasone 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. Many factors are taken into consideration by your myeloma doctor when determining your dose of dexamethasone, including age and fitness. The use of low-dose dexamethasone has been well established.  

Dexamethasone is usually prescribed at a dose of 20 mg to 40 mg once-weekly. For patients who cannot tolerate these doses, dexamethasone has proven to be effective at doses as low as 4 mg once-weekly. For more information about dexamethasone, read the IMF’s publication Understanding Dexamethasone in the Treatment of Myeloma. 

Thalidomide in the Maintenance Setting  

Thalidomide has been tested extensively in the maintenance setting. In the British MRC IX study in 2012, thalidomide was demonstrated to improve progression-free survival (PFS), but not overall survival (OS) in newly diagnosed patients who had received a wide variety of prior therapies. In that study, maintenance thalidomide was given at 50 mg/day, increasing to 100 mg/day after 4 weeks, if tolerated, and continuing until progression. Thalidomide at the low 50–100 mg/day dose level remains an option for maintenance therapy. In 2017, a study published in the journal Leukemia compared maintenance therapy with thalidomide and Velcade to either thalidomide alone or recombinant interferon alpha-2b alone in newly diagnosed myeloma patients after their induction therapy. Recombinant interferon alpha-2b is an antiviral and anticancer drug with immune-modulating effects. After a median follow-up of 58.6 months, median PFS was significantly longer with thalidomide and Velcade than with either of the other two therapies alone. There was no significant difference in overall survival between the three maintenance therapy arms.

Thalidomide in the 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. Thalidomide continues to be studied in clinical trials. For up-to-date information, contact the IMF InfoLine or visit clinicaltrials.gov. For a broader discussion about clinical trials, read the IMF publication Understanding Clinical Trials in Myeloma. 

Possible Side Effects of Thalidomide 

 The REMS program  

Thalidomide can cause severe birth defects or the death of a developing fetus. Thalidomide should never be used by women who are pregnant or who could become pregnant while taking the drug. Thalidomide may be detected in male sperm. For that reason, both males and females of reproductive potential must follow strict rules for birth control while taking thalidomide. 

In the U.S., the FDA’s Risk Evaluation and Mitigation Strategy (REMS) program is a mandatory safety measure for medications with serious safety concerns. The aim of the REMS program is to help ensure that the benefits of the medication outweigh its risks. To minimize the risk of exposure for an unborn child, the thalidomide REMS program includes the following requirements:  

• Male and female patients must provide informed consent, complete confidential enrollment, and complete follow-up surveys throughout treatment with thalidomide.  
• Females of reproductive potential must have pregnancy tests every week during the first month of thalidomide therapy. Afterwards, females with regular menstrual cycles must have pregnancy tests monthly, and females with irregular menstrual cycles must have pregnancy tests every 2 weeks. Females must receive contraceptive counseling and use 2 methods of birth control 4 weeks before, during, and at least 4 weeks after completing thalidomide therapy. 
• Males with female partners of reproductive potential must use a latex condom during and until at least 4 weeks after completing thalidomide therapy. 

Drowsiness 

Thalidomide often causes drowsiness, a feeling of being sleepy and lethargic. Talk to your doctor about methods that may help relieve drowsiness, such as taking thalidomide at bedtime, avoiding alcohol, avoiding other drugs that may contribute to feelings of drowsiness, and taking medication prescribed by your doctor to alleviate drowsiness.  

Drowsiness may impair your mental and physical abilities. This may be problematic or dangerous in certain situations. For example, you may need help from your care partners with tasks such as driving a car.  

Peripheral neuropathy  

Peripheral neuropathy (PN) is a serious condition that affects 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 such as thalidomide. Symptoms may include a feeling of numbness, tingling, burning, and/or pain 

Alert your doctor as soon as you begin experiencing any symptoms of PN. Typically, PN from thalidomide occurs after a long period of taking this drug, but it can occur sooner. Ask your doctor about walking and other forms of exercise. Avoid tight shoes and socks with elastic. Your doctor may reduce your dose of thalidomide or prescribe additional medications. If your PN is severe, thalidomide therapy may need to be discontinued. 

Dizziness  

Dizziness may occur during treatment with thalidomide. Sitting up and waiting a few minutes before standing or getting out of bed may help reduce dizziness. Report any occurrences of dizziness to your doctor.  

Constipation 

The medical definition of constipation is 3 or fewer bowel movements within 1 week. The stool may be hard, dry, and difficult to pass. You may also experience stomach cramps or bloating. Constipation may occur during treatment with thalidomide, but it is rarely severe. Prevention is the key to management.  

Discuss with your doctor strategies that may help alleviate constipation, such as how much fluid you should drink daily, if consuming dietary fiber is appropriate, and which form of exercise may be helpful. Do not take stool softeners or laxatives without first asking your doctor. If your constipation is severe, your doctor may lower your dose of thalidomide or it may be temporarily discontinued.  

Rash 

A rash may develop while taking thalidomide. A mild rash is red or discolored skin, with or without raised bumps, which usually begins on the body and spreads to the arms and legs. Ask your doctor if taking anti histamines or topical steroids is appropriate for your rash. Using oatmeal soap and calendula or cocoa butter cream may help with dry skin. Some rashes are a potentially serious reaction to thalidomide. Rare reactions include Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN). Symptoms of Stevens-Johnson syndrome include persistent fever, rash, blisters, or red splotches on the skin and blisters in the mouth, eyes, ears, nose, and genital area. TEN is characterized by blistering and peeling of large sections of skin. Contact your doctor immediately if a fever or a drop in blood pressure occur.  

Leukopenia  

Your doctor will monitor your blood counts for leukopenia, which is a decrease in white blood cells (WBC). If your WBC count becomes too low, your dose of thalidomide may be lowered or interrupted.  

Other side effects 

Other side effects have been reported, although infrequently. Promptly report to your doctor all the side effects you experience while receiving treatment for myeloma. In addition, any changes in your overall health or well-being should also be reported to your doctor. 

Additional Information

Thalomid® website

Celgene's website for Thalomid® with information on clinical information, prescribing guidelines, benefits and risks, and so forth.

Patient Assistance

Celgene's Patient Support Coordinator Program

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 Thalomid.

Fast Track for First Prescription™

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. A Celgene Patient Support coordinator will ensure that “all the ducks are in a row” as quickly as possible, and remove the hurdles to accessing that first cycle of medication. To be eligible, patients must be receiving their first prescription of either Thalomid or Revlimid, 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 800-452-2873.

Clinical Trials

Open Thalomid® (thalidomide) Trials

Clinical trials list from clinicaltrials.gov.