Recognizing, Preventing, and Treating Toxicities
The most common toxicities that occur with agents used to treat patients with multiple myeloma are neuropathy, thromboembolism, myelosuppression (eg, thrombocytopenia, neutropenia, and anemia), and infections. Thalidomide and lenalidomide should not be used during pregnancy.38,39 Bisphosphonate therapy can cause flu-like symptoms, renal impairment, and ONJ.

Neuropathy
Table 2Bortezomib and thalidomide are associated with peripheral neuropathy that is predictable but manageable with patient monitoring; the potential for higher response rates must be weighed against increased adverse effects and requires individual patient consideration.38,40
  
Evaluation of peripheral neuropathy in patients receiving chemotherapy can be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) (Table 2).41 Once the grade of neuropathy is determined, appropriate supportive care can be provided.
  
If severe cases of peripheral neuropathy occur with bortezomib, patients may be managed with dose modification or discontinuation (Table 3). Those with pre-existing severe neuropathy should be treated with bortezomib only after a careful assessment of risk and benefit.40


Table 3Thromboembolism
Use of thalidomide and lenalidomide has resulted in increased risk of thromboembolic events such as DVT and pulmonary embolism in patients with multiple myeloma. When either agent is used in combination with dexamethasone, this risk is increased significantly.38,39 In one controlled trial, the rate of VTE events was 22.5% in patients receiving thalidomide in combination with dexamethasone vs 4.9% in patients receiving dexamethasone alone (P = .002).38 Risk is highest in patients who receive high-dose dexamethasone, doxorubicin, or multiagent chemotherapy in combination with thalidomide or lenalidomide.42
  
Clinicians and patients should observe for signs and symptoms of thromboembolism, and patients should be instructed to seek medical care if they develop symptoms such as shortness of breath, chest pain, or arm or leg swelling.38,39 Preliminary data suggest that patients receiving thalidomide who are appropriate candidates may benefit fromconcurrent prophylactic anticoagulation or aspirin treatment38; however, it is not known whether prophylactic anticoagulation or antiplatelet therapy prescribed in combination with lenalidomide may lessen the potential for VTE. Decisions regardingprophylactic measures should be made carefully after an assessment of an individual patient’s underlying risk factors.39
  
Table 4Palumbo et al have proposed that individual risk factors for VTE associated with thalidomide- or lenalidomide-based therapy are age, history of VTE, central venous catheter, comorbidities (eg, infection, diabetes, cardiac disease), immobilization, surgery, and inherited thrombophilia. Multiple myeloma–associated risk factors for thromboembolism include the diagnosis of multiple myeloma and hyperviscosity.Using a risk assessment model, prophylaxis isbased on the number of risk factors. For example, aspirin is recommended for ≤1 risk factor and low-molecular-weight heparin (eg, enoxaparin 40 mg/d) for patients with ≥2 individual or myeloma-related risk factors and in all patients receiving concurrent high-dose dexamethasone or doxorubicin. Data are limited on the use of full-dose warfarin targeting a therapeutic international normalized ratio of 2 to 3, and newer agents have not yet been studied in this population.42

Table 5Myelosuppression
Bortezomib, thalidomide, and lenalidomide may cause hematologic toxicities such as thrombocytopenia and neutropenia. For anemia caused by bortezomib and lenalidomide when used in combinations, epoetin or darbepoetin may be indicated for hemoglobin levels ≤10 g/dL along with 25% to 50% reduction in dose.43 Suggested dose modification for bortezomib when administered in conjunction with melphalan and prednisone is summarized in Table 4.40
  
Recommended management for patients with multiple myeloma who develop thrombocytopenia or neutropenia while receiving treatment with lenalidomide are summarized in Table 5.39

 

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