Thromboprophylaxis in Multiple Myeloma: Indian Perspective

Background: Hypercoagulability has been observed in patients of multiple myeloma and has been associated with deep venous thrombosis (DVT). There is growing evidence of increased rate of venous thromboembolism associated with use of thalidomide, an anti angiogenesis drug, especially when combined with other agents such as dexamethasone and doxorubicin. Currently there is no consensus on the most appropriate prophylactic approach for thrombotic episodes in patients of multiple myeloma treated with thalidomide containing regimen. Although newer thalidomide derivatives with less thrombogenic adverse effects are being used in the developed countries, in developing countries like India due to financial constraints thalidomide remains the 1^st line drug for multiple myeloma. Further there are scant reports of multiple myeloma related thrombosis and thrombo prophylactic regimen from developing countries.

Objectives: To evaluate the incidence of symptomatic as well as asymptomatic thrombosis at onset of the disease as well as during treatment, the efficacy of low dose aspirin and low molecular weight heparin as thromboprophylaxis and their adverse effects in multiple myeloma patients treated with thalidomide and dexamethasone regimen.

Patients and Methods: 30 patients of multiple myeloma reporting to our centre from May 2006 to March 2008 comprised the study group. Patient with past history of bleeding, thrombocytopenia and deranged coagulation parameters were excluded from the study. The male to female ratio was 3:2. The median age was 56 years (39–70). 23 patients were de-novo and 7 patients were relapse cases. Before starting therapy in addition to diagnostic and prognostic work up, all patients were evaluated for symptomatic as well as asymptomatic DVT with the help of Color Doppler Flow Index (CDFI) study and d-dimer estimation. Patients were randomized to low dose aspirin (Aspirin 150 mg once a day) and low molecular weight heparin (Enoxapirin 40 mg once a day). All patients were administered dexamethasone pulses of 40 mg once a day from day 1 to 4 in each cycle of 28 days. Thalidomide was started at a dose of 100mg once a day and increased to maximum of 400 mg depending on tolerability (median dose 200 mg). None of the patients received erythropoietin. All patients were evaluated for DVT at the beginning of each cycle during the first three cycles. Thromboprophylaxis was administered for first three cycles only. The response to therapy was evaluated at completion of 3^rd and 6^th cycles. Criteria for response were as previously reported by Blade et al.

Results: The overall response (OR) after 3 cycles was 18/30 (60%), complete response (CR)-10/30(33.3%), partial response (PR)-8/30(26.7%) and after 6 cycles was 22/28 (78.5%), CR-16/28(57.1%), PR-6/28(21.4%). 2 patients who had progressive disease after 3 cycles were changed to Bortezumib containing regimen. Out of 30 patients only one patient (3.3%) a 70 yr old male had deep vein thrombosis at diagnosis which was asymptomatic and the diagnosis was based on CDFI findings. One patient on low dose aspirin had one episode of upper GI bleed on 5^th day of the first cycle and thromboprophylaxis was stopped. During the follow up, none of the patient had any evidence of symptomatic as well as asymptomatic DVT.

Conclusion: This study suggests that the incidence of venous thrombosis in our cohort of patients were much lower than reported from the west. Both low doses Aspirin as well as low molecular weight heparin are effective agents for thromboprophylaxis. The adverse effects were acceptable. Larger trials would be required to confirm these findings.