Venous thromboembolism prophylaxis in multiple myeloma patients receiving immunomodulatory therapy: a systematic review and meta-analysis.

Patients with multiple myeloma receiving immunomodulatory drugs have an increased risk of venous thromboembolism (VTE), but the comparative effectiveness and safety of available prophylactic strategies remain uncertain. A systematic review and meta-analysis of randomized and prospective studies was conducted in accordance with PRISMA 2020. Studies evaluating aspirin, low-molecular-weight heparin (LMWH), warfarin, direct oral anticoagulants (DOACs), or no prophylaxis in patients receiving immunomodulatory therapy were included. Primary outcomes were symptomatic VTE and major bleeding. Twelve studies (n=2,435; 25 arm-level observations) were included. Descriptive pooled VTE incidence was 2.2% with apixaban, 5.1% with rivaroxaban, 5.6% with LMWH, 7.9% with aspirin, 9.1% with warfarin and 20.9% with no prophylaxis; these single-arm estimates are descriptive summaries of heterogeneous arms rather than adjusted between-class comparisons. LMWH significantly reduced VTE compared with warfarin, and aspirin reduced VTE compared with no prophylaxis. Major bleeding rates were low across active prophylaxis groups (0.3-1.6%). Evidence certainty was low or very low for every included study and very low for all DOAC evidence, reflecting small, heterogeneous and largely non-randomised studies. Active thromboprophylaxis is associated with substantially lower VTE incidence than no prophylaxis in patients with multiple myeloma receiving immunomodulatory therapy. Among established agents, LMWH has the most robust evidence base, though that base is itself of low certainty. Observations relating to DOACs, including apixaban, rest exclusively on very low certainty evidence from small prospective cohorts and feasibility studies and are strictly hypothesis-generating. Because the evidence is dominated by thalidomide-era regimens whereas contemporary therapy has evolved substantially, external validity to modern practice remains limited, and adequately powered randomised trials in current regimens are needed.