Multiple Myeloma and Thrombosis: Prophylaxis and Risk Prediction Tools

Abstract

Thromboembolism in multiple myeloma (MM) patients remains a common complication that renders the optimization of our thromboprophylaxis practice necessary. This review aims to make clear the need for the development of more accurate risk assessment tools and means of thrombosis prevention. Current clinical practice is guided by available guidelines published by the IMWG in 2014, but the extent to which these are implemented is unclear. Recently, several groups developed clinical scores for thrombosis risk in MM in an attempt to improve risk stratification, but these have not been validated or used in clinical practice so far. Research in this field is increasingly focusing on understanding the unique coagulation profile of the MM patient, and data on potential biomarkers that accurately reflect hypercoagulability is emerging. Finally, promising evidence on the effectiveness of direct oral anticoagulants (DOACs) in the context of thrombosis prevention in MM patients is increasingly becoming available. The critical appraisal of the above research areas will establish the necessity of combining disease-specific clinical risk factors with coagulation biomarkers to allow more effective risk stratification that will eventually lead to the reduction of this significant complication. Results from ongoing clinical trials on the role of DOACs are much anticipated.

A Real-Life Survey of Venous Thromboembolic Events Occurring in Myeloma Patients Treated in Third Line with Second-Generation Novel Agents

“…The poor concordance with IMWG guidelines regarding ASA or LMWH use for VTE prophylaxis in MM patients has been well documented in other studies dealing with "real life" experiences [48]. A retrospective French study conducted on 236 patients treated with an IMiDs-based regimen demonstrated that only 43% high-risk and 34% low-risk patients received a thrombo-prophylaxis [19].…”

“…One of the reasons for the poor adherence of physicians to the IMWG indications could be related to the fact that the definition of the risk of developing a VTE remains too vague and the different parameters used to define the risk are equally considered, while they have probably a different strength as risk factors [48,49]. For example, the use of erythropoietin is considered a risk factor in the same way as others, but it must be taken into account that erythropoietin increases the risk of developing VTE especially when it determines a significant increase in hematocrit and hemoglobin (Hb) [19,55].…”

“…As shown in Figure 2, in all, 10 (9%) patients treated with new agents developed VTE, including 7 uncomplicated DVT and 3 pulmonary embolism (PE). As shown in Table 2, no patients had therapy-related risk factors, including high dose dexamethasone defined as more than 480 mg/month [48]. All patients in the KRd and Daratumumab groups had at least one individual risk factors.…”

“…All patients in the KRd and Daratumumab groups had at least one individual risk factors. Among MM-related risk factors we included hyperviscosity defined as IgG >15 g/dL, IgA >10 g/dL and for IgM >3 g/dL [48], present in five patients: two treated with pomalidomide and thre with KRd. Detailed analysis of both individual and MM-related risk factors for each treatment group is reported in Table 3.…”

“…Little is known about vascular toxicity of Carfilzomib [46] and more studies are needed to understand the underlying mechanism of endothelial injury [46,47]. Concerning ixazomib, elotuzumab and daratumumab, VTE is not reported as an adverse event for these drugs; thus, no thromboprophylaxis is currently recommended [5,7,48]. However, recommendations on next generation myeloma drugs are derived from clinical trials where patients are selected and do not fully reflect the heterogeneity of patients in the real-life setting, in the presence of multiple risk factors for VTE [17,[48][49][50].…”