Abstract

Background The pathogenesis of thalidomide induced DVT is poorly understood. It has been suggested that effect may involve a direct action of thalidomide on endothelial cells previously damaged by chemotherapy agents. The purpose of the present study was to examine the efficacy of daily low-dose (81 mg orally) in decreasing the incidence of venous thromboembolic events (VTE’s) in patients with multiple myeloma receiving thalidomide plus dexamethasone as primary therapy and the comparison with a control group of MM patients without aspirin.

Material and methods Patients with newly diagnosed multiple myeloma treated with thalidomide plus dexamethasone were assigned to receive aspirin at lower doses and were compared with an historical cohort of patients without thromboprophylaxis. We enrolled patients who fulfilled entire criteria for multiple myeloma between January 2003 and May 2006. Thalidomide was prescribed in an oral dose of 100 mg qhs and increased by 50 mg every 7 days to a maximum dose of 200 mg, depending on side effects. Dexamethasone was given in an oral dose of 20 mg/m2 each morning after breakfast on days 1–4, 9–12 and 17–20, followed by 10 days without therapy prior to the next cycle. Treatment combination was continued for at least 6 months or until the earliest occurance of maximum plateau of myeloma protein reduction, autologous transplant-supported intensification or other treatments. Coagulations tests and thrombosis: Citrate plasma was used to investigate coagulation and anticoagulation parameters. The coagulations tests include: prothrombin time, activated partial thromboplastic time (aPTT), fibrinogen, anticardiolipin antibodies, lupus anticoagulant, antithrombin III, protein C and protein S activities, activated protein C (APC) resistance, Factor V Leiden, and D-dimers.

Results Sixty multiple myeloma patients treated with thalidomide plus dexamethasone were included. Patients were assigned to receive either aspirin at a dose of 81 mg qd (newly diagnosed, n20) or nothing (newly diagnosed n20, relapsed n10 or refractory n10). DVT was developed in 7 patients (17.5%) in the NARG (Non aspirin group) and only in 1 patient for the ARG (5%, Aspirin receiver group) P0.005. Five patients were confirmed to have acquired activated C protein resistance (NARG 4/ARG1). Known risk factors for DVT, such as central venous catheters (CVC) (present in 16% patients), performance status, and hormonal therapy were not significantly different between these 2 groups of patients (all p values >0.2) None patient has prior history of DVT and neither one was receiving anticoagulation at the time of enrollment.

Conclusions Low dose aspirin (81 mg) given daily to patients with newly diagnosed and relapsed/refractory MM treated with thalidomide plus dexamethasone. To fully evaluate the potential synergistic anticancer activity of combinations of chemotherapy and thalidomide, effective prophylactic anticoagulation should be implemented in all controlled trials, at least during the first few cycles of treatment.

Disclosure: No relevant conflicts of interest to declare.

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