Thalomid®

What is Thalomid?

Thalomid (thalidomide, Celgene) is an oral cancer drug that was originally developed in the 1950s as a treatment for insomnia and morning sickness. Further research on Thalomid showed it to be highly active against myeloma. When the findings of that research were published in 1999, Thalomid was considered to be the first new agent with major activity against myeloma in more than 30 years.

Thalomid is part of a class of drugs called immunomodulatory drugs (IMiDs). IMiDs work against cancer cells partly by supporting the functioning of the immune system.


How is Thalomid used in multiple myeloma?

Thalomid in combination with dexamethasone is approved for the treatment of patients with newly diagnosed multiple myeloma.

The National Comprehensive Cancer Network (NCCN), which develops guidelines for cancer treatments based on evidence from clinical trials, suggests that Thalomid-dexamethasone can also be used in combination with Velcade (bortezomib, Takeda Oncology) for treatment before transplantation.

Another combination recommended by NCCN as an alternative treatment option for patients with newly diagnosed or relapsed/refractory disease is dexamethasone-Thalomid-cisplatin-doxorubicin-cyclophosphamide-etoposide (DT-PACE) with or without Velcade (VTD-PACE).

How does Thalomid work?

Thalomid increases the immune system’s response against myeloma cells, but its precise mechanism of action is unknown. The drug appears to have multiple actions, including the ability to inhibit the growth and survival of myeloma cells in a variety of ways.

Recently, it has been shown in studies funded by the Multiple Myeloma Research Consortium (MMRC) that Thalomid and other IMiDs bind a protein in myeloma cells called cereblon. This binding triggers myeloma cell death. In some studies, higher levels of cereblon are associated with better outcomes after treatment.

What types of individuals benefit from Thalomid?

Thalomid-based treatment has been shown to be effective in a wide range of patients with multiple myeloma.

Patients who should not take Thalomid include:

  • Pregnant or nursing women (male and female individuals of childbearing potential must be willing to take extreme precautions to avoid pregnancy, including registering with the Thalomid Risk Evaluation and Mitigation Strategies (REMS) program)
  • Patients with a history of moderate peripheral neuropathy or of blood clots (known as deep vein thrombosis or DVT) because of the increased risk of these conditions as a side effect

How is Thalomid administered?

Thalomid is administered orally and is available as 50 mg, 100 mg, 150 mg, and 200 mg capsules. According to the manufacturer’s label, the dose of Thalomid is 200 mg per day. However, doctors may choose to start treatment at a lower dose to help reduce the likelihood of side effects. When the starting dose is lower, it may be gradually increased by 50 mg or 100 mg to achieve maximum effectiveness, and patients are monitored closely to ensure that side effects remain manageable. For best results, Thalomid should be taken once daily with water, preferably at bedtime, and at least 1 hour after the evening meal.

When used in combination with dexamethasone, Thalomid is taken once daily in 28-day treatment cycles. The standard dose of dexamethasone is 40 mg, taken on days 1–4, 9–12, and 17–20 of each month for the first 4 months. Starting at month 5, dexamethasone is taken only on days 1–4 of each month.

The optimal length of treatment with Thalomid has not been determined. Patients with multiple myeloma typically continue to take Thalomid as long as the side effects remain manageable and disease does not progress.

Doctors evaluate the response to treatment with Thalomid after about 1 month. Some sign of benefit may be seen within this time, but it is usually 2–3 months before response occurs. Because a response can often improve with continued treatment, discontinuing Thalomid therapy after a short period of time may fail to provide the full therapeutic benefit of the drug. Increasing the dose slowly and managing side effects may help individuals continue treatment with Thalomid. Once a good response has been achieved, the doctor may reduce the Thalomid dose for maintenance therapy.

For patients who do not have a response after 3 months of treatment, a doctor may increase the dose of Thalomid or may add another drug to the treatment regimen.


What are Thalomid side effects?

Thalomid side effects have been observed in clinical studies. The side effects associated with Thalomid can range from mild to severe, and not all patients experience them. It is important to note that the frequency of side effects usually increases as the dose of Thalomid is increased. The incidence of severe side effects is low, and severe side effects appear to be related to higher doses of the drug.

 

Fatigue and peripheral neuropathy, a disorder of the nerves that can result in abnormal or decreased sensation or burning/tingling in the hands and feet, are usually the most common reasons for discontinuing treatment with Thalomid. Other side effects seen in clinical studies of Thalomid-dexamethasone include:

  • Blood clots
  • Low blood calcium levels (hypocalcemia)
  • Swelling (edema)
  • Constipation, nausea
  • Difficulty breathing
  • Fatigue, muscle weakness, or lack of energy
  • Low white blood cell and neutrophil counts
  • Rash, dry skin, or  skin reactions resulting in blistering or peeling
  • Lack of appetite, weight loss, weight gain
  • Fever
  • Confusion, anxiety/agitation, dizziness, clumsiness, tremor

Side effects can usually be minimized or controlled by reducing the dose of Thalomid or by using an appropriate strategy to manage a particular side effect.

Serious side effects

The most serious side effect associated with Thalomid is its effect on a fetus. If Thalomid is taken immediately prior to conception or at any time during pregnancy, the drug is associated with serious birth defects, including malformed limbs, gastrointestinal disorders, and fetal death. To ensure that Thalomid is used safely, Celgene has developed a unique restricted distribution program called Thalomid REMS. Individuals eligible to receive Thalomid must be registered in the program.

Deep-vein thrombosis (DVT), a blood clot that develops and obstructs blood flow in one of the large veins in the legs (or less commonly, the arms), is a side effect of Thalomid that can be serious if not recognized and treated. Signs and symptoms of DVT include an area on one limb that is warm, painful, or tender to the touch; is reddened or discolored; or feels hardened. Patients that have any of these symptoms  should contact their doctor immediately.

The risk of DVT is higher when Thalomid is used with dexamethasone and some chemotherapy agents, such as doxorubicin. However, patients receiving Thalomid also receive preventative treatment with a blood thinner (anticoagulant). The choice of agent is based on a patient’s individual risk factors for blood clots and may include aspirin, a low-molecular weight heparin, or warfarin.

Other Thalomid side effects that can be severe at times include peripheral neuropathy, increased risk of death, dizziness and low blood pressure, drowsiness/sleepiness, heart attack and stroke, decreased heart rate, low neutrophil count, seizures, and skin reactions resulting in blistering or peeling.


What have Thalomid clinical studies shown?

Is Thalomid effective in previously untreated myeloma?

Thalomid clinical studies have shown that adding Thalomid to one or more other drugs to treat newly diagnosed/untreated multiple myeloma has improved response rates and survival time. Combination therapies that include Thalomid have been shown to be effective for patients who are to have stem cell transplantation.

Several studies have shown the combination of Thalomid-dexamethasone plus Velcade (bortezomib, Takeda Oncology) to be more effective than Thalomid-dexamethasone when given prior to stem cell transplantation. For example, in one study involving 255 patients, Thalomid-dexamethasone-Velcade led to a complete response (before transplantation) of 36% compared with 9% for Thalomid-dexamethasone alone. The rate of complete response after transplantation was 57% for Thalomid-dexamethasone-Velcade and 28% for Thalomid-dexamethasone alone.

Is Thalomid effective for relapsed/refractory myeloma?

Thalomid is used in combination with a variety of other agents in the treatment of relapsed/refractory myeloma. Combination therapy that includes Thalomid-dexamethasone and the chemotherapy agents cisplatin, doxorubicin, cyclophosphamide, and etoposide (referred to as DT-PACE) with or without Velcade (VTD-PACE) was shown to be an effective alternative treatment for progressive disease.

Updated March 2019

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