Adverse effects of thalidomide administration, in patients with myeloma multiplex?

Myeloma multiplex is defined by the presence of monoclonal plasma cell population in the bone marrow>10%,M protein in the serum and/or urine ,and clinical evidence of end organ damage like hypercalcemia ,renal failure, anemia, or bone lesions. In the most hematologic malignancies the role of induction treatment is to achieve complete remission (CR). Thalidomide became a new therapeutic approach but use of Thalidomide as a single agent or combination with steroids or chemotherapy is associated with several side effects like deep vein thrombosis (DVT), peripheral neuropathy (PN), constipation, somnolence, pyrexia, pain, fatigue osteonecrosis of jaw, and teratogenicity that is the most worrying adverse event. Risk of appearance of DVT increased if we use combination of Thalidomide plus Dexamethasone plus cytotoxic chemotherapy such Cyclophosphamide. >30% DVT usually occurs during the first months of treatment and is more frequent in newly diagnosed patients with a high tumor burden. The second side effect is peripheral neuropathy (PN) which occurs in 50% of patients with MM treated with Thalidomide plus Dexamethasone and chemotherapy.

Eighty patients of both sexes (43 males and 37 females) at the age of 31-81 (median range 58 years) with MM, were treated-one group with combinations of Thalidomide plus Dexamethasone plus Cyclophosphamide (CyThalDex) 4 cycle(>4months), and the other group with Thalidomide plus Dexamethasone plus Melphalan (MPT), (>4month) and third group with high dose of chemotherapy and continue with ThalDex (TD), the fourth group with CyThalDex, > than 5 cycles, and the fifth group with ThalDex (TD) only.

It is obvious while myelo-suppression is very rare, the incidence of nonhematologic side effects is high and dose dependent. Eight (or 10%) patients that developed DVT and CVI were initially treated with antiaggregation therapy of Aspirin 100mg per day, but those that already developed were treated with low dose of Heparin 40000 iE per day in ten days and continued with oral anticoagulans therapy. However, besides the given therapy in four (or 5 %) patients there was exitus letalis. PN was developed in twentyone patients (or 26.25%) from the total number of patients treated with Thalidomide, in ten patients the dosage of Thalidomide was decreased to 50mg per day, in one patient with Epi attacks it was interrupted and the other was with paresis n.occulomotorius and n.abducens.

Patients treated with thalidomide have an increased risk of arterial thromboembolism, including myocardial infarction and cerebrovascular events, in addition to the established risk of venous thromboembolism, but most patients who presenting DVT or some of thromboembolic events have had identifiable risk factors. The prolonged exposure to Thalidomide seems to induce resistance of MM reducing overall survival (OS). We must evaluate consolidation and maintenance therapies with Thalidomide, determinate which regimens provide a highness benefit with favorable side effect profiles in specific subgroups of patients.