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• W3168080535 abstract "Venous thromboembolism (VTE), which comprises deep-vein thrombosis and pulmonary embolism, is a well-described complication of cancer leading to significant morbidity and mortality. It was first described in 1865 by Armand Trousseau who recognized the association between thrombophlebitis migrans and cancer.1 However, it was only in 2002 that Prandoni and colleagues reported that patients with active malignancy have a threefold higher risk of VTE recurrence compared to non-cancer patients while on therapeutic warfarin for treatment of an acute venous thromboembolic event [hazard ratio (HR) = 3·2; 95%, confidence interval (CI) = 1·9–5·4].2 Subsequently, a number of clinical trials followed to compare different treatment strategies for cancer and VTE, assess primary thromboprophylaxis in cancer and to predict VTE risk in ambulatory cancer patients.3-9 Multiple myeloma (MM) encompasses 10% of all haematological cancers and 1% of all cancers. It affects mainly individuals at age 70 or older and it is slightly more prevalent in males (1·3:1·0).10 Amongst the haematological malignancies, myeloma has the highest incidence of VTE followed by acute leukaemias and lymphomas.11-15 Interestingly, different from solid tumours, VTE is not associated with disease aggressiveness or mortality risk in myeloma.16 Nevertheless, the pathophysiology of VTE in myeloma has several similar aspects to solid tumours. It is directly associated with patient-, therapy- and disease-related factors that will trigger both the primary and secondary phases of coagulation through overproduction and expression of P-selectin, von Willebrand factor, vascular endothelial growth factor and pro-inflammatory cytokines that will perpetuate the activation of the coagulation cascade and stimulate neo-angiogenesis.14, 15, 17-22 The hypercoagulability characteristic of myeloma may be further exacerbated by agents commonly used to treat MM: immunomodulatory drugs (IMiDs), alkylating agents, dexamethasone; and the less frequently used, but also pro-thrombotic doxorubicin. Despite the known hypercoagulable state related to MM, there is significant equipoise in which is the best thromboprophylaxis strategy for those patients given the published studies have not been appropriately powered to assess the efficacy and safety of the various anticoagulant medications in this population. Our group has summarized these data on a systematic review of trials that included MM patients on lenalidomide-based therapy.23 We demonstrated the heterogeneity in reporting of VTE risk assessment and we found that aspirin (ASA) is the most frequent thromboprophylaxis option used regardless of patients’ individual VTE risk stratification. The preference for ASA over low-molecular-weight heparin (LMWH) may be explained by the avoidance of self-injection and the high cost of LMWH. Low-dose ASA is oral, widely available, inexpensive and effective for the prevention of VTE in various clinical settings.10, 24, 25 The International Myeloma Working Group (IMWG) VTE risk criteria were developed by consensus to try to mitigate the risk of VTE in myeloma patients on IMiDs.26 It includes several potential predictors such as BMI > 30 kg/m2, previous VTE, central venous lines, comorbidities, immobilization and use of IMiDs or doxorubicin, among others. Low-dose ASA (81–325 mg daily) is recommended for those with one or no risk factors; LMWH or warfarin for those with more than one risk factor. Unfortunately, the IMWG criteria are largely based on expert opinion and it was never appropriately, systematically or prospectively evaluated or validated. Recently, Sanfillippo and colleagues evaluated 4 446 MM patients on IMId-based therapy and retrospectively derived the IMPEDE VTE score for risk stratification of VTE in MM patients.27 The score incorporated several of the risk factors included in the IMWG criteria, namely IMIDs; BMI; Pelvic, hip or femur fracture; use of ESAs, use of Dexamethasone/Doxorubicin; Ethnicity/Race; VTE history; central venous lines; and Existing thromboprophylaxis. The six-month cumulative incidence of VTE showed good discrimination with 3% for low-risk, 8% for intermediate and 15% for high-risk patients. Subsequently, IMPEDE VTE was externally validated and confirmed its reproducibility using the SEER-Medicare database; even though information on BMI and use of ASA were lacking for assessment of the accuracy and generalisability of the prediction model.27 Regardless, this was a first very important step towards understanding the potential independent predictors of VTE in MM. In the current issue of BJH, Covut et al. have successfully externally validated the IMPEDE VTE score. They were able to demonstrate the validity, generalisability and robustness of the score in a large cohort of 575 newly diagnosed MM patients followed at the Cleveland Clinic in the US. As in Sanfillippo et al., the six-month cumulative incidence rate of VTE was 10·7% in the overall study population, in which VTE occurred in only 5% of the low-risk and 24% of the high-risk category. They also demonstrated that Eastern Cooperative Oncology Group (ECOG) performance status may be a relevant independent predictor that needs to be further evaluated in future studies. This is a highlight of the study given ECOG is an important predictor of frailty in myeloma.28, 29 It is imperative to note, however, that a clinical prediction rule (CPR) is an algorithmic decision-making tool that, ideally, is derived from original research using strict methodological guidelines. CPRs are appealing because they offer several potential benefits for practitioners, patients and the Health Care System, such as reduction in the clinical uncertainty at the bedside and improvement in quality of care for patients, and may decrease exposure to costly and potentially hazardous or unnecessary procedures. Wasson published the methodological standards for clinical prediction rules which were later on updated.30-32 Among other criteria, ideally, a CPR should be prospectively derived and the reproducibility of the clinical findings used as predictive variables must be demonstrated. The IMPEDE VTE score has been derived and validated in retrospective studies only. This is a potential weakness of the score. Nevertheless, the score was assessed in different myeloma populations which confirms its generalisability and there was a good concordance amongst them, confirming its reproducibility. In the future, it will be important to further validate the score in a prospective trial and consider the relevance, efficacy and safety of direct oral anticoagulants in this context." @default.
• W3168080535 created "2021-06-22" @default.
• W3168080535 creator A5046056355 @default.
• W3168080535 date "2021-06-01" @default.
• W3168080535 modified "2023-10-17" @default.
• W3168080535 title "Thrombosis and myeloma: it is time to get the elephant out of the room" @default.
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• W3168080535 doi "https://doi.org/10.1111/bjh.17507" @default.
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