An expert panel of European hematologists has published guidelines for treating newly diagnosed multiple myeloma patients with thalidomide (Thalomid) in addition to melphalan (Alkeran) and prednisone. The guidelines are intended to help physicians and patients manage the side effects commonly associated with thalidomide treatment.

For the last four decades, the standard front-line therapy for newly diagnosed myeloma patients who are ineligible for stem cell transplantation has been a combination regimen of melphalan and prednisone (MP). However, the results from five Phase 3 clinical trials have indicated that the addition of thalidomide to MP (MPT) significantly improved response rates over MP alone.

Two studies demonstrated that patients receiving MPT had an extended survival time of 18 months, compared to patients receiving only MP. Other studies noted that the addition of thalidomide resulted in a longer median progression-free survival or superior event-free survival.

Based on the findings of these five trials, MPT was recently approved for the treatment of newly diagnosed, transplant-ineligible myeloma patients in Europe.

However, thalidomide is associated with several known side effects, including blood clots, low blood cell counts, pain in patients’ legs and arms, and skin rashes.  An expert panel of European hematologists therefore agreed to develop and publish guidelines on how to effectively manage thalidomide’s side effects.

Blood Clots

Patients receiving thalidomide as a first-line treatment have an increased risk of venous thromboembolism (VTE), a condition in which a blood clot forms in a vein, limiting the blood flow in the affected vein. It is also possible for part of the clot to break off, travel through the vein, and block an artery to the lungs. Studies have noted that the occurrence of VTE was highest during the first four months of MPT treatment.

In developing an appropriate treatment plan, the panel advised physicians to assess if the patient has any additional VTE risk factors, which include high-dose dexamethasone (Decadron) treatment, diabetes, infections, cardiovascular disease, immobility, prior history of VTE events, hormone replacement therapy, and a central venous catheter.

The panel recommended that high-risk patients receive 40 mg daily of low molecular weight heparin for a duration of four to six months. Low-risk patients should receive 100 mg of aspirin during the full treatment period and for 30 days following discontinuation of thalidomide treatment.

Low Blood Cell Counts

Although a reduction in blood cell production (cytopenia) has been observed in patients receiving MP, the addition of thalidomide increases the severity and incidence of this side effect. Researchers noted that up to 15 percent of patients receiving MPT experienced low platelet counts and low red blood cell counts (anemia), and up to 50 percent experienced low white blood cell counts (neutropenia).

The panel recommended that prior to a new cycle of MPT, physicians should assess a patient’s blood counts. If the blood counts are low, physicians should delay treatment for two weeks and reassess blood counts before starting a new treatment cycle. Once treatment begins, the thalidomide and melphalan dosage should be reduced, and patients should receive granulocyte colony stimulating factor (G-CSF), which is a hormone that stimulates white blood cell production.

Tingling And Pain In Extremities

Patients receiving thalidomide-based treatment commonly experience pain in the legs and arms, known as peripheral neuropathy. Patients with this condition may feel numbness, tingling, discomfort, and abnormal coordination or weakness.

The panel recommended that physicians assess patients prior to and during treatment; if a patient exhibits symptoms of peripheral neuropathy, the dose of thalidomide should be reduced.

Slow Heartbeat

Thalidomide may also induce an abnormally slow heartbeat (bradycardia), which is associated with dizziness, weakness, and possibly convulsions or sudden cardiac death.

The panel recommended that all patients undergo a cardiologic examination prior to starting thalidomide treatment. Physicians should continue to monitor patients during therapy; if a patient exhibits symptoms of bradycardia, the dose of thalidomide should be reduced or treatment should be discontinued.

Skin Rashes

Skin rashes are frequent complications with thalidomide treatment. Minor to moderate skin reactions have been observed in 46 percent of patients, with up to 6 percent experiencing more severe and possibly life-threatening skin reactions.

The panel recommended that in the most severe cases, treatment should be discontinued until the severity is reduced to mild; the treatment can then be restarted at 50 percent of the original dose. If a patient experiences a toxic reaction, such as Stevens-Johnson Syndrome, treatment with thalidomide should be permanently discontinued.

Birth Defects

If taken immediately before conception or during pregnancy, thalidomide may cause severe, life-threatening birth defects. The panel noted that most countries require patients to participate in a risk management plan.

The panel concluded that the MPT drug combination is an effective treatment for patients ineligible for stem cell transplants. Physician and patient awareness of thalidomide’s side effects and optimal management of these side effects may maximize the treatment’s efficacy and lead to further improvements in response and survival rates.

For more information, please read the panel’s recommendations in the journal Annals of Hematology (abstract).