Venous Thromboembolism Prophylaxis with Aspirin for Multiple Myeloma Patients Receiving Thalidomide Combination As First-Line Treatment
Authors: Crusoe Edvan de Queiroz , Massarenti Mariana , Almeida Manuella , Cury Priscilla , Higashi Fabiana , Vieira Luiza , Rossato Marina , Peres Ana Lucia , Castro Anna Carolina , Silva Ana Luiza , Hungria Vania T M 
Published: October 2019

Abstract
Introduction: Despite the increase in overall survival in patients with multiple myeloma (MM) over the last decade as a result of the use of new chemotherapeutic agents, the immunomodulators (thalidomide and lenalidomide) are associated with a higher rate of venous thromboembolism (VTE), principally when associated with other chemotherapeutic drugs and erythropoietin (EPO). The incidence of VTE with isolated thalidomide is 3 to 4%, similar to the risk of the disease itself. The association of thalidomide with corticoids or anthracycline agents has led to an increase in the incidence of VTE to 12 and 34%, respectively. The introduction of low-dose aspirin, vitamin K inhibitors or low molecular weight heparin prophylaxis, according to the risk factors present upon diagnosis reduced the risk of thrombosis to 3 to 7%.
Objectives: The objectives were to evaluate thrombotic events during the use of thalidomide as first-line treatment in symptomatic MM patients and the effectiveness of low-dose aspirin prophylaxis.
Casuistic and Methods: This is a descriptive study of thrombotic events by means of a retrospective survey of patient files for MM patients who had been followed up on at the gammopathies outpatient unit at Santa Casa de Misericórdia de São Paulo from January 2009 to April 2014. The following induction therapy schedules with thalidomide for patients eligible or not for bone marrow transplantation were performed: thalidomide + dexamethasone (TD), cyclophosphamide + thalidomide + dexamethasone (CTD) and melphalan + prednisone + thalidomide (MPT). All of the patients received a dose of 100mg/day of the antiplatelet agent (aspirin) as prophylaxis.
Results: In the aforementioned period, 219 patients had been diagnosed with symptomatic MM and of these, 149 patients had received thalidomide-based chemotherapy. The thalidomide group had a median age of 61 years (40 to 88). In the DS IIIA-IIIB stage, there were 131 (87.9%), 14 (9.4%) IIA-IIB, 1 (0.7%) IA and 3 (2%) had not been evaluated. According to the ISS Classification, 36 (24.2%) were ISS I, 41 (27.5%) II and 58 (38.9%) III, with 9.4% not evaluated. The most frequent isotope was IgG (56%). In relation to chemotherapy, 34 (22.8%) received TD, 98 (65.8%) CTD, 17 (11.4%) MPT. We identified 10 (6.7%) cases of thrombotic events in patients using thalidomide, thus distributed: 8 deep vein thrombosis (DVT), one case of DVT/ pulmonary embolism and one case of thrombophlebitis. Only one patient with thrombosis did not follow the prophylactic treatment at the service, which was 100mg/day of aspirin. The events occurred on average 72 days after initiating thalidomide use. Five cases were related to mobility reduction, 2 cases to obesity, 2 to smoking, 3 being ex-smokers, 3 to infection concomitant with the thrombotic event, 2 to diabetes and 1 case of previously treated breast cancer. All of the cases presented some associated risk factor.
Conclusion and Discussion: The use of aspirin as prophylaxis in the group of MM patients being treated with thalidomide demonstrated efficacy in the control of risk for thrombosis. We observed 6.7% of VTE with the prophylactic use of low-dose aspirin in recently diagnosed MM patients without a history of thrombotic events, as described in the literature. Thalidomide is made available free of charge for MM treatment by the Brazilian public health system. Therefore, it is the main drug used in the MM treatment in Brazil. A better understanding of adequate thrombophylaxis according to the present risk factors is important for the optimization of the treatment of MM patients.

Disclosures
No relevant conflicts of interest to declare.