A systematic review of direct oral anticoagulants for thromboprophylaxis in multiple myeloma

Abstract

Multiple myeloma (MM) is associated with increased venous thromboembolism (VTE) risk. Current guidelines recommend aspirin or low-molecular-weight heparin for thromboprophylaxis depending on VTE risk. Nevertheless, VTE risks remain high: a recent meta-analysis reported an incidence of 6.2% during the entire MM course. Direct oral anticoagulants (DOACs) showed promising results in other malignancies. This systematic review provides an overview of evidence on DOAC thromboprophylaxis in MM. PubMed and Embase were searched up to November 21, 2023, for studies evaluating MM and DOAC thromboprophylaxis (PROSPERO: CRD42022376152). Two authors independently screened titles, abstracts, and texts, assessed bias using a modified version of the Newcastle Ottawa Scale and certainty of evidence with the Grading of Recommendations Assessment, Development and Evaluation approach, and performed data extraction and analysis. Seven articles comprising 416 patients with DOAC thromboprophylaxis were included, primarily involving newly diagnosed patients with MM (56.3%) receiving lenalidomide-based regimens (69.1%). Overall Newcastle Ottawa Scale study quality was moderate. Four studies reported follow-up duration ranging from 90 days after induction to 7 months. VTE proportions ranged from 0% to 23.5%, with 4 studies reporting 0%. The proportions of minor, clinically relevant nonmajor, and major bleeding ranged from 0% to 18.2%, 0% to 7.7%, and 0% to 4.5%, respectively. Arterial thrombosis proportions ranged from 0% to 2.9%. Only 2 studies reported on mortality (2% and 7.1%). Overall Grading of Recommendations Assessment, Development and Evaluation certainty of evidence was very low for all outcomes. Current evidence regarding routine DOACs in MM is insufficient, warranting further research to establish the DOAC thromboprophylaxis risk-to-benefit ratio in MM.

Keywords: anticoagulants; multiple myeloma; systematic review; thrombosis; venous thromboembolism.

Figure

Flowchart of article selection and inclusion. ∗443 duplicates removed from first search and 33 duplicates from second search. ∗∗1318 articles screened during first search and 150 articles during second search. ∗∗∗6 articles included from first search and 1 article from the update search. AT, arterial thromboembolism; DOAC, direct oral anticoagulant; MM, multiple myeloma; RCT, randomized controlled trial; VTE, venous thromboembolism. Records identified from other: from manual screening of appropriate systematic review references.