MM-450: Anti-Thrombotic Therapy for Ambulatory Patients with Multiple Myeloma Receiving Immunomodulatory Agents: A Systematic Review

Abstract

Context Multiple myeloma (MM) is a malignant plasma cell disorder characterized by clonal plasma cells and is associated with an increased risk of thromboembolism, especially in people receiving immunomodulatory agents, including lenalidomide, pomalidomide, and thalidomide. Objective 1) To systematically review the evidence for the relative efficacy and safety of anticoagulants in MM patients; and (2) to maintain this review as a living systematic review. Design Comprehensive literature search that included (1) major electronic searches (February 2021) of the following databases: CENTRAL, MEDLINE, and Embase; (2) conference proceedings; (3) reference lists of included studies; and (4) ongoing studies in trial registries. As part of the living systematic review approach, we are running continual searches on a monthly basis. Setting Randomized controlled trials (RCTs). Participants Ambulatory people with MM receiving immunomodulatory agents who otherwise have no standard therapeutic or prophylactic indication for anticoagulation. Interventions Any of: Aspirin (ASA), vitamin K antagonist (VKA), low-molecular-weight heparin (LMWH), or direct oral anticoagulants (DOAC). Main Outcomes Measures All-cause mortality, symptomatic deep vein thrombosis (DVT), pulmonary embolism (PE), major bleeding, and minor bleeding. Results Of 1004 identified citations, we included nine articles reporting four RCTs that enrolled 813 participants. ASA versus VKA: One RCT compared ASA to VKA at six months and at two years follow-up. The data did not confirm or exclude a beneficial or detrimental effect of ASA relative to VKA on studied outcomes. ASA versus LMWH: Two RCTs compared ASA to LMWH at six months and at two years follow-up. The pooled data failed to confirm or exclude a beneficial or detrimental effect of ASA relative to LMWH on studied outcomes. VKA versus LMWH: One RCT compared VKA to LMWH at six months and at two years follow-up. The data did not confirm or exclude a beneficial or detrimental effect of VKA relative to LMWH on studied outcomes. ASA versus DOAC: One RCT compared ASA to DOAC at six months follow-up. The data did not confirm or exclude a beneficial or detrimental effect of ASA relative to DOAC on studied outcomes. Conclusions People with MM considering anti-thrombotic agents should balance the possible benefits of reduced thromboembolic complications with the possible harms and burden of anticoagulants.