Thromboprophylaxis in patients with multiple myeloma.

Abstract

Malignancy is a strong risk factor for venous thromboembolism (VTE), either from the malignancy itself or from other factors such as cancer treatments.1 VTE can lead to morbidity and mortality, delay cancer treatments, and increase hospitalisations and healthcare utility. Multiple myeloma (MM) is associated with a 4- to 7·5-fold increased risk of VTE compared with age- and sex-matched controls, with highest risk observed in the year following MM diagnosis, and in patients exposed to immunomodulatory drugs.2 Therefore, effective VTE prevention strategies are crucial in this patient population. International guidelines have recommended thromboprophylaxis with aspirin or low-molecular-weight heparin (LMWH) in patients with MM receiving immunomodulatory agents.3 However, aspirin poorly prevents VTE, and LMWH has not been adopted routinely as primary thromboprophylaxis given the burden and cost of daily injections. In recent years, two large randomised controlled trials, the AVERT and CASSINI studies, established the role of apixaban and rivaroxaban respectively, as primary thromboprophylaxis in ambulatory cancer patients with Khorana score ≥ 2 starting chemotherapy.4, 5 However, patients with MM were underrepresented in these studies, with only 15 out of 574 (2·6%) patients in the AVERT study and none in the CASSINI study. The applicability of Khorana score to patients with MM has also been challenged,6 and they were not included in the initial population from which Khorana score was derived.7 Therefore, whether direct oral anticoagulants (DOACs) can be effective and safe thromboprophylactic options in patients with MM remains unclear. Cornell and colleagues report their results of a single arm pilot study of using apixaban 2·5 mg orally twice daily as primary thromboprophylaxis in 50 patients with MM receiving immunomodulatory agents. Over the study period of six months, no patients developed VTE (the primary efficacy outcome) nor major bleeding complications (part of the composite primary safety outcome), and only three developed clinically relevant non-major bleeding events (another part of the composite primary safety outcome). In addition, no arterial thrombotic events were observed. The results are encouraging, although this may be a relatively ‘lower risk’ group, given that 40% of patients were on maintenance therapy with a low disease burden and a low dose of immunomodulatory agents with or without dexamethasone. Recently two risk stratification models, the SAVED and IMPEDE VTE scores, have been developed in the MM population.8, 9 Li et al. identified a high-risk group representing 30% of MM patients, with a six-month cumulative VTE incidence of 11–12%, while Sanfilippo et al. identified 10% of MM patients in the highest risk group with a six-month cumulative incidence of VTE of >15%.8, 9 These unacceptable rates of thrombosis urge evaluation of new tailored thromboprophylaxis strategies using DOACs to achieve an optimal risk:benefit ratio. This pilot study is important because it establishes the feasibility of larger trials investigating thromboprophylaxis in patients with MM. It also opens ways to further important trials assessing thromboprophylaxis in high-risk patients with other haematological malignancies. Specific VTE risk assessment models have already been developed for acute leukaemia (Al-Ani risk score), myeloproliferative diseases (IPSET-thrombosis), or lymphoma (ThroLy score).10-12 However, to date, only one randomised pilot trial assessing a DOAC for thrombosis prevention in adult patients with malignant haematologic conditions has been registered with ClinicalTrials.gov. This pilot study will assess the feasibility of a full-scale trial comparing a prophylactic dose of apixaban to aspirin in addition to cytoreductive therapy in patients with JAK2-positive myeloproliferative neoplasm (NCT04243122). In light of the AVERT and CASSINI studies, evaluation of the potential benefits of DOACs for the prevention of thrombosis in patients with haematological malignancies is urgently needed.