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Venous thromboembolism (VTE) is a common cause of morbidity and mortality among patients with multiple myeloma (MM). The International Myeloma Working Group (IMWG) developed guidelines recommending primary thromboprophylaxis, in those identified at high‐risk of VTE by the presence of risk factors. The National Comprehensive Cancer Network (NCCN) has adopted these guidelines; however, they lack validation. We sought to develop and validate a risk prediction score for VTE in MM and to evaluate the performance of the current IMWG/NCCN guidelines. Using 4446 patients within the Veterans Administration Central Cancer Registry, we used time‐to‐event analyses to develop a risk score for VTE in patients with newly diagnosed MM starting chemotherapy. We externally validated the score using the Surveillance, Epidemiology, End Results (SEER)‐Medicare database (N = 4256). After identifying independent predictors of VTE, we combined the variables to develop the IMPEDE VTE score (Immunomodulatory agent; Body Mass Index ≥25 kg/m2; Pelvic, hip or femur fracture; Erythropoietin stimulating agent; Dexamethasone/Doxorubicin; Asian Ethnicity/Race; VTE history; Tunneled line/central venous catheter; Existing thromboprophylaxis). The score showed satisfactory discrimination in the derivation cohort, c‐statistic = 0.66. Risk of VTE significantly increased as score increased (hazard ratio 1.20, P = <.0001). Within the external validation cohort, IMPEDE VTE had a c‐statistic of 0.64. For comparison, when evaluating the performance of the IMWG/NCCN guidelines, the c‐statistic was 0.55. In summary, the IMPEDE VTE score outperformed the current IMWG/NCCN guidelines and could be considered as the new standard risk stratification for VTE in MM.

IntroductionPlatelets arise as cytoplasmic fragments from megakaryocytes in the bone marrow. Thus they are anucleate, but retain megakaryocyte-derived cytoplasmic pre-mRNA, at least some of which is spliced into mRNA and translated into protein in response to external stimulation through surface receptor activation and outside-in signaling. [1][2][3] Previously unrecognized synthetic capabilities of platelets have recently emerged and the profi le of proteins released by activated platelets (the "secretome") has been well characterized. 4Prior studies have shown that the platelet transcriptome correlates well with platelet proteomic data, demonstrating that transcriptional analysis is relevant to the study of platelet biology, and can likely provide insights into platelet function and the mechanisms of platelet disorders. In one study, platelet proteomic data correlated well with the transcriptome, with 69% of secreted proteins detectable at the mRNA level.5 Using microarray analysis, Gnatenko et al reported that approximately 2,000 transcripts (13-17% of probed genes) are present in unstimulated platelets and concluded that evaluating the platelet transcriptome will be useful for identifying proteins that regulate normal and pathologic platelet functions. 6Platelets play a major role in the metastatic dissemination of tumor cells in vivo .7-10 Because of the leaky vasculature of angiogenic tumors, platelets are in contact with tumor cells and are therefore able to secrete multiple factors upon activation. 11Numerous tumor cell lines (e.g. MDA-MB-231 breast cancer cells) interact with platelets and stimulate platelet aggregation in vitro . 12Th e requirement of platelets for murine lung metastasis to occur has been long recognized and antibody-induced thrombocytopenia has been shown to markedly reduce the number and volume of metastasis associated with Lewis lung carcinoma, CT26 colon adenocarcinoma, and B16 amelanotic melanoma. 13Platelets facilitate metastasis through multiple mechanisms. [11][12][13][14][15] Tumor cell survival in the circulation is helped when they nest within platelet aggregates-this shields them from natural killer cell-mediated cell death and the eff ects of vascular shear stress. Platelets facilitate adhesion of blood-borne cancer cells to endothelium through selectins, along with transmigration at metastatic sites where they also enhance angiogenesis and release growth factors such as PDGF that have been shown to act as a mitogenic stimulus. While these observations are well accepted, the detailed mechanisms behind them remains uncertain. 16In this study, we sought to identify the relationship between platelet gene expression and lung cancer metastasis and surprisingly found near universal downregulated expression of the 200 genes with the most altered expression. Th ese genetic fi ndings further support the long-held view that platelet function is signifi cantly altered in the presence of cancer metastasis and that screening employing the tools outlined here may form the basis of an ef...