IMWG GUIDELINES FOR THE PREVENTION OF THALIDOMIDE- AND LENALIDOMIDE-ASSOCIATED THROMBOSIS IN MYELOMA¹

The risk of VTE in cancer patients is greater than 7%; those with myeloma have the highest risk of thrombosis.² The oral immunomodulatory drugs, thalidomide and lenalidomide, further increase that risk. The following guidelines from the International Myeloma Working Group recommend a prophylaxis strategy based upon a risk assessment model. The recommendations have been made in the absence of clear data from randomized studies, and are therefore based on common sense and on data extrapolated from many studies not specifically designed to answer these questions. Treatment decisions must be based on the type of therapy and the patient’s individual risk factors.

Risk factors for venous thromboembolism (VTE) in myeloma patients

• Individual
• Obesity (defined as body mass index > 30kg/m²)
• Previous venous thromboembolism
• Central venous catheter or pacemaker
• Associated disease
• Cardiac disease
• Chronic renal disease
• Diabetes
• Acute infection
• Immobilization
• Surgery
• General surgery
• Any anesthesia
• Trauma
• Medications
• Erythropoietin
• Blood clotting disorders
• Myeloma-related risk factors
• Diagnosis per se
• Hyperviscosity
• Myeloma therapy (all are to be considered high-risk factors)
• High-dose dexamethasone
• Doxorubicin
• Multiagent chemotherapy

Recommendations for VTE prophylaxis in myeloma patients based on risk factors
Both individual and myeloma-related risks of VTE should be taken into account in determining the type of thromboprophylaxis.

• If no risk factor, or any one risk factor is present, aspirin 81-325 mg once daily is recommended.
• If two or more risk factors are present, LMWH (equivalent of enoxaparin 40 mg once daily) or full-dose warfarin, international normalized ratio (INR) 2-3, is recommended.
• If any myeloma therapy-related risk factor is present, then LMWH (equivalent of 40 mg enoxaparin once daily) or full-dose warfarin (target INR 2-3) is recommended.

Recommendations for VTE prophylaxis in myeloma patients based on type of therapy

• Thalidomide
• Patients receiving single-agent thalidomide: anticoagulation therapy not recommended
• Newly diagnosed patients receiving thal/dex: full-dose warfarin
• Newly diagnosed patients treated with combinations that include melphalan (i.e. MPT): low-molecular-weight heparin (LMWH)
• Newly diagnosed patients treated with thalidomide + multiagent chemotherapies: LMWH, low-fixed-dose warfarin, and full-dose aspirin not effective
• Newly diagnosed patients treated with thal + doxorubicin when the regimen contains bortezomib: LMWH effective
• Relapsed patients: anticoagulant prophylaxis suggested only in those with a high risk of VTE
• Lenalidomide
• Patients receiving single-agent lenalidomide: anticoagulation therapy not recommended
• Patients receiving lenalidomide plus low-dose dexamethasone,  melphalan, or doxorubicin: aspirin recommended (if no or one risk factor present)
• Patients receiving high-dose dexamethasone: LMWH or full-dose warfarin recommended

Diagnosis and Management of VTE

• Diagnosis
• Compression ultrasonography the diagnostic test of choice for suspect VTE
• Computed tomography (CT) pulmonary angiography most widely used diagnostic test for pulmonary embolism (PE)
• Magnetic resonance pulmonary angiography may be used as an alternative to CT pulmonary angiography in patients who have a contraindication to iodinized contrast media
• Treatment
• Patients should be instructed to inform the physician if any of the following symptoms occur:
• Redness of the skin
• Pain in the extremities or chest
• Shortness of breath
• Rapid heartbeat
• Appropriate initial therapy for patients with DVT is LMWH
• Discontinue therapy with thalidomide or lenalidomide and resume when full anticoagulation has been established
• If risk of thrombocytopenia is low, oral anticoagulation should be started on the first day of treatment
• Heparin should be given for a minimum of 5 days and not stopped until a patient’s INR is from 2.0-3.0 for 2 consecutive days
• Extended therapy with LMWH should be considered, balancing its advantages with disadvantages such as cost, the need for daily injections, and the risk of osteoporosis