Full Length Article Thromboprophylaxis in multiple myeloma patients treated with lenalidomide – A systematic review Fatimah Al-Ani a,b, ⁎, Jose Maria Bastida Bermejo c , María-Victoria Mateos c , Martha Louzada a,b a University of Western Ontario, Hematology Division, London, Ontario, Canada b Hematology Division, London Health Sciences Center, London, Ontario, Canada c University of Salamanca, Hematology Division, Salamanca, Spain abstract article info Article history: Received 1 September 2015 Received in revised form 1 February 2016 Accepted 4 March 2016 Available online 5 March 2016 Background: Studies have consistently demonstrated the need for venous thromboembolism (VTE) prophylaxis in patients with newly diagnosed multiple myeloma (NDMM) or relapsed refractory multiple myeloma (RRMM), receiving lenalidomide-based therapy. However, the optimal approach has not yet been established. Objective: To compare the efficacy of aspirin (ASA) and low molecular weight heparin (LMWH) prophylaxis in patients with myeloma using lenalidomide-based therapy. Results: Six studies were included with 1125 adult participants with NDMM or RRMM treated with lenalidomide- based therapy with thromboprophylaxis with ASA or LMWH. Pooled data of studies of NDMM showed that the risk of VTE in patients on ASA was 1.5 per 100 patient-cycles with a total risk of VTE of 98 of 915 (10.7%) [95% CI: 8.86–12.88] compared to 3 of 211 (1.4%) [95% CI: 0.48–4.09] with LMWH in NDMM and RRMM patients. Our study demonstrated a significantly higher VTE risk for patients receiving lenalidomide plus high-dose dexa- methasone (RD) on ASA prophylaxis compared to lenalidomide plus low-dose dexamethasone (Rd) [RR = 2.5 (95% CI: 1.68–3.96), P b 0.0001]. Furthermore, patients who received lenalidomide and dexamethasone alone had a significantly higher risk of VTE compared to those on MPR while on ASA prophylaxis (RR = 6.4 [(95% CI: 4.11–9.91), P b 0.0001]). Conclusion: The most frequent thromboprophylaxis option used for myeloma patients on lenalidomide-based therapy is ASA. However, ASA may not confer appropriate thromboprophylaxis in patients using RD, but may be a safe option with MPR. In future studies, the IMWG VTE risk stratification criteria should be validated, incor- porating the thromboprophylaxis option accordingly. More studies comparing the efficacy and safety of ASA to LMWH are warranted. © 2016 Elsevier Ltd. All rights reserved. 1. Background Malignancy is a well-recognized risk factor for venous thromboem- bolism (VTE) [1]. In the general population the annual incidence of VTE is estimated to be 1 to 2 per 1000. In patients with cancer, this risk is 5 to 28-fold higher, depending on various patient and malignancy characteristics [2–4]. In multiple myeloma the incidence of VTE varies between 3% and 10% [5]. Immunomodulatory drugs (IMiDs) play a cru- cial role in the treatment of multiple myeloma and are known to be as- sociated with an increased risk of VTE, particularly in the first four to six months of treatment [6]. In addition, it appears that patients with newly diagnosed multiple myeloma (NDMM) are at higher risk for VTE com- pared to patients with relapsed or refractory myeloma (RRMM) at the start of IMiD therapy [6]. Lenalidomide is a second-generation IMiD which in combination to high or low-dose dexamethasone has shown to be an effective and well-tolerated treatment for patients with both NDMM and RRMM [7–9]. It is becoming the new backbone for myeloma treatment both in clinical trials and in clinical practice [7–11]. Nevertheless, studies have consistently demonstrated the need for VTE prophylaxis in pa- tients receiving the combination lenalidomide-dexamethasone [9,12]. It is well documented that in RRMM, this combination treatment is as- sociated with a 4.4-fold increased risk for VTE compared to dexametha- sone alone in the absence of a prophylactic anticoagulants [7]. Furthermore, in NDMM receiving the same combination VTE rates can be as high as 67% compared to 15% in RRMM [7]. Several different thromboprophylaxis strategies have been effective in lowering the risk of VTE but data are disputable and randomized studies are scarce [3]. In the two randomized trials MM-009 and MM- 010, although used on an individual basis, prophylactic anticoagulation was not mandated [7,8]. Recently, Larocca and colleagues have com- pared the use of aspirin (ASA) with low molecular weight heparin (LMWH) prophylaxis in NDMM patients treated with lenalidomide Thrombosis Research 141 (2016) 84–90 ⁎ Corresponding author at: Hematology Division, London Health Sciences Center, 800 Commissioners Rd E, Rm E6-218, London, Ontario, N6A 5W9, Canada. E-mail address: alani.fatimah99@gmail.com (F. Al-Ani). http://dx.doi.org/10.1016/j.thromres.2016.03.006 0049-3848/© 2016 Elsevier Ltd. All rights reserved. Contents lists available at ScienceDirect Thrombosis Research journal homepage: www.elsevier.com/locate/thromres Descargado de ClinicalKey.es desde Consejeria de Sanidad de Castilla y Leon(Sacyl) mayo 13, 2016. Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2016. Elsevier Inc. Todos los derechos reservados.