Universal Use of Novel Oral Anticoagulant Prophylaxis in Myeloma Patients Undergoing IMiD-Based Therapy: Real-World Experience

Background/Objectives: Multiple myeloma (MM) patients receiving immunomodulatory drugs (IMiDs) are at increased risk of venous thromboembolism (VTE). Standard prophylaxis typically involves aspirin or low-molecular-weight heparin (LMWH), guided by risk assessment tools such as SAVED and IMPEDE-VTE. However, these models have practical limitations, and real-world evidence supporting novel oral anticoagulants (NOACs) as primary prophylaxis remains limited. Methods: In this retrospective, single-center study, we analyzed 101 MM patients treated with IMiD-based therapy between January 2020 and December 2024. All patients received NOAC prophylaxis (apixaban 2.5 mg twice daily or rivaroxaban 10–20 mg once daily), irrespective of baseline thrombotic risk. Clinical characteristics, comorbidities, and treatment details were collected. The primary outcome was objectively confirmed VTE, while secondary outcomes included bleeding events and treatment feasibility, assessed by treatment continuation without clinically significant bleeding. Results: Median age was 63 years (range 35–89); 36.6% were female. Lenalidomide and pomalidomide were used in 86.1% and 13.9%, respectively. Twenty-eight patients (27.7%) had relapsed/refractory disease, while 72.3% were newly diagnosed. Over a median NOAC exposure of 6 months, two patients (2.0%) developed VTE (both deep vein thrombosis). One major bleeding event (1.0%) occurred. Conclusions: Universal NOAC prophylaxis in MM patients receiving IMiD-based therapy was associated with a low incidence of thromboembolic events and an acceptable safety profile. These real-world findings suggest that NOACs may represent a practical and effective alternative to aspirin or LMWH, potentially overcoming the limitations of score-based prophylaxis strategies.