title: Clinical and genetic factors associated with venous thromboembolism in myeloma patients treated with lenalidomide-based regimens.
abstract: Lenalidomide has significant antimyeloma activity but it is associated with a significant risk of venous thromboembolism (VTE). In this study, we assessed clinical and genetic risk factors that may predispose for VTE in myeloma patients who were treated with lenalidomide-based regimens. We analyzed common clinical and selected genetic factors in 200 consecutive, unselected myeloma patients who were treated with lenalidomide-based regimens in a single institution. Twelve patients (6%) developed a VTE (nine deep venous thrombosis and three pulmonary embolism). All VTEs occurred in patients who were receiving aspirin prophylaxis; no patient who received LMWH or acenocoumarol had a VTE. The frequency of VTEs was 9.4% in previously untreated and 4.5% in previously treated patients. VTEs were more frequent in patients >65 years (8.1% vs. 1.6%) especially among patients receiving aspirin as prophylaxis (10.4% vs. 1.8% for patients ≤65 years). In patients who received prophylaxis with low dose aspirin a single-nucleotide polymorphism in NFκB1 (rs3774968) gene was associated with increased risk of VTE (OR 3.76, 95%CI 1-16, P = 0.051). None of the patients who developed VTEs had common genetic variations that are associated with increased risk of VTEs in the general population, such as FVLeiden and FIIG20210A. Our data indicated that LMWH or vitamin K antagonists (with a target INR 2-3) effectively reduce the risk of VTEs. In patients who received prophylaxis with aspirin genetic variants of genes that are involved directly or indirectly in inflammatory response may be associated with increased risk of VTE.
authors.affiliation: Department of Clinical Therapeutics, University of Athens, School of Medicine, Athens, Greece.
authors.forename: Tina
authors.initials: T
authors.lastname: Bagratuni
authors.forename: Efstathios
authors.initials: E
authors.lastname: Kastritis
authors.forename: Marianna
authors.initials: M
authors.lastname: Politou
authors.forename: Maria
authors.initials: M
authors.lastname: Roussou
authors.forename: Efthimios
authors.initials: E
authors.lastname: Kostouros
authors.forename: Maria
authors.initials: M
authors.lastname: Gavriatopoulou
authors.forename: Evangelos
authors.initials: E
authors.lastname: Eleutherakis-Papaiakovou
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Kanelias
authors.forename: Evangelos
authors.initials: E
authors.lastname: Terpos
authors.forename: Meletios A
authors.initials: MA
authors.lastname: Dimopoulos
mesh_terms: D000074:Acenocoumarol / Q000627:therapeutic use; D000367:Age Factors; D000970:Antineoplastic Agents / Q000009:adverse effects; D001241:Aspirin / Q000009:adverse effects; D005260:Female; D020022:Genetic Predisposition to Disease; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects; D000077269:Lenalidomide; D008297:Male; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D021122:Protein Subunits / Q000235:genetics*; D011655:Pulmonary Embolism / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control; D013792:Thalidomide / Q000009:adverse effects / Q000031:analogs & derivatives*; D020246:Venous Thrombosis / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control
chemical_list: D000970:Antineoplastic Agents; D006495:Heparin, Low-Molecular-Weight; D007155:Immunologic Factors; D016328:NF-kappa B; D021122:Protein Subunits; D013792:Thalidomide; D000077269:Lenalidomide; D000074:Acenocoumarol; D001241:Aspirin