Incidence of Venous Thromboembolism in Patients with Hematologic Malignancies Receiving Immunomodulators and Concurrent Anticoagulation Therapy: A Single-Center Retrospective Study

Introduction:The incidence of venous thromboembolism (VTE) has been shown to be 28-times higher in patients with hematologic malignancies when compared with the general population. Among all of the hematologic malignancies, multiple myeloma has been associated with the highest risk for VTE. The pathophysiology of VTE in multiple myeloma is complex and the exact mechanism has not been fully elucidated. Prior studies have found a higher risk of VTE in patients with newly diagnosed multiple myeloma receiving combination therapies when compared with patients with relapsed or refractory disease. In addition to the disease itself, myeloma treatment and individual patient factors may also contribute to the risk of VTE. Oral immunomodulators (IMiDs) such as thalidomide, lenalidomide, and pomalidomide are the mainstay of myeloma treatment. Immunomodulators have been shown to improve response rate in myeloma patients but further increase the risk of VTE, especially when given in combination with dexamethasone and other chemotherapy agents.

The International Myeloma Working Group (IMWG) and the National Comprehensive Cancer Network (NCCN) recommend the use of thromboprophylaxis in myeloma patients receiving immunomodulator-based regimens. Enoxaparin or warfarin are recommended in patients with two or more risk factors or in patients receiving high-dose dexamethasone, doxorubicin or combination chemotherapy, while aspirin is recommended in patients with one or no known risk factors. However, the selection of the most appropriate thromboprophylaxis remains challenging due to the lack of an accurate risk prediction model. Several studies have demonstrated a reduced rate of VTE after implementation of thromboprophylaxis in myeloma patients receiving IMiDs. Another study found no statistical significant difference in the incidence of developing a first episode of thrombosis in previously untreated myeloma patients receiving thromboprophylaxis with warfarin, aspirin, or enoxaparin. This suggests that all three agents may have similar efficacy but the results may not be applicable to all myeloma patients. Conversely, a more recent observational study found an overall significantly higher rate of VTE in patients who received thromboprophylaxis with aspirin than with a vitamin K antagonist. Since the publication of these studies, there has also been a rise in the prescribing rates of new oral anticoagulants (NOACs) despite limited evidence for the use in patients with cancers. Given the mixed results that are demonstrated by prior research and the utilization of a new class of agents, further investigation is needed to establish the efficacy of different thromboprophylaxis strategies.

Objectives: Our primary objective is to determine the incidence of VTE episodes in patients with hematologic malignancies receiving an immunomodulator-based regimen and any concurrent anticoagulation therapies. Our secondary objectives are to classify anticoagulation therapies being used in combination with IMIDs, to identify the relationship between occurrence of new acute thrombosis and various anticoagulation therapies and to determine the clinical efficacy of different aspirin doses that are used for thromboprophylaxis.

Methods: This single center, retrospective study will include patient data from July 1, 2014 to December 31, 2016. Patients who are 18 years old and above are eligible for inclusion if they received at least 2 documented consecutive cycles of an oral IMID (thalidomide, lenalidomide, and pomalidomide) for a hematologic malignancy with or without concurrent anticoagulation therapy. Patients are only included if their IMiD prescriptions were written by one of the hematologists at our cancer center. Patients receiving IMiDs while enrolled in a clinical trial are also allowed for inclusion in our analysis. Basic demographic information, relevant past medical history, concurrent chemotherapy, anticoagulation agents, and rates of VTE will be collected through a review of the electronic medical record. Chi-square or Fischer's exact test will be used for group comparison of categorical variables and Mann-Whitney U test will be used for the comparison of continuous variables.

Results: In process.