Predicting the risk of venous thromboembolism in newly diagnosed myeloma with immunomodulatory drugs: External validation of the IMPEDE VTE score
Authors: Emilie Chalayer, Alice Teste, Denis Guyotat, Ismail Elalamy, Xavier Leleu, Bernard Tardy
Journal: American Journal of Hematology (2019)

In patients with multiple myeloma (MM), starting treatment increases the risk of venous thromboembolic event (VTE) by over 10% a year.1 This is due to the patient's risk factors as well as the type of chemotherapy prescribed1. Thus, we found great interest in the article by Sanfilippo et al. reporting on the first risk assessment score, the IMPEDE VTE score in order to evaluate VTE risk in newly diagnosed MM (nMM) starting any chemotherapy.2 We strongly agree with the author's perspective. Indeed, MM does require specific management because of the common use of corticosteroids like dexamethasone and agents such as immunomodulatory drugs (IMiDs) which increase the risk of VTE.3 According to current guidelines, thromboprophylaxis is advised in treated MM based on VTE risk stratification. However, VTE risk factors are still unclear except IMiDs initiation and a recombinant erythropoietin (rEPO) treatment.3, 4 The issue was raised in a French large prospective multicenter observational study including 524 MM patients receiving IMIDs either in first, second or third line of chemotherapy (MELISSE).4 This study aimed at assessing the VTE incidence and the associated risk factors. VTE was reported at 4 and 12 months. We decided to carry on a new analysis of the MELISSE database, computed the IMPEDE VTE score so as to evaluate the accuracy of this score in the screening of VTE risk in patients with nMM patients starting chemotherapy, in French real-life practice. In the MELISSE database, 190 patients were treated for nMM. The median age of the study population was 75.5 years old and the sex ratio was 1.21 (male/female). The characteristics of patients and VTE risk factors are available in the previous publication about MELISSE database3 and specific IMPEDE VTE items in the Table 1. VTE was defined as objectively-confirmed pulmonary embolism (PE) and/or deep vein thrombosis (DVT). VTE was specifically asked in the MELISSE case report form. A total of 177 patients were evaluable with an incidence of 7.3% VTE events at 6 months (95% CI 4.1-12.4; 8 PE and 9 DVT). Using R software, our Receiver Operating Characteristic (ROC) curve was 0,65. The IMPEDE VTE score ranged from −3 to +10, with a median of 3 (IQR 3-4, n = 13) in the thrombosis group whereas the median was 2 (IQR 1,8-4, n = 164) in the group without thrombosis (P = .08, Wilcoxon test). A total of 118 patients (67%) were classified as low risk by the score (≤3), 53 (30%) as intermediate risk (4-7) and 6 (3%) as high-risk (≥7). VTE was diagnosed in 7 patients (5.9%) of the low-risk IMPEDE VTE score group, in 6 (9.4%) of the intermediate and in one patient (16.7%) of the high-risk group. The ROC in MELISSE database and the San Filippo c-statistic (both internal and external validation) are similar. They show only a modest discriminating ability of the score. The addition of biomarkers such as thrombin generation evaluation to improve IMPEDE VTE should be considered as a potential incremental for the score performance in a future study.5 In addition, regarding the intermediate and high-risk groups, our results seem similar to the IMPEDE VTE cohort. Contrariwise, our VTE risk in the low-risk group was 5.9% whereas it was 3.3% in IMPEDE VTE (representing 67% of our patients vs 52%). Our database focused on IMiDs drug, with 100% of the patients under IMIDs vs 44% in the IMPEDE VTE cohort. This can explain why there is a difference between VTE incidences in both studies. However, when the score is computed without negative points due to thromboprophylaxis, only 8% of patients had a low-risk (no VTE reported in this group). In the San Filippo cohort, the sample was nationwide so very few women and few Asians and pacific Islanders were part of it. In France, few people are from Asia or Pacific Islands according to our national data (INSEE). So we can suppose the lack of such data did not impact our study. For Sanfilippo et al, thromboprophylaxis should be avoided in low-risk population. This still needs proving. In our opinion, neither a 3.3% nor a 5.9% early-VTE incidence should allow no thromboprophylaxis. Moreover, can we really consider heparin and aspirin as equal thromboprophylaxis? Pooling together prophylactic by heparin and aspirin to prevent thrombosis seems arguable. There is no denial that the score could be improved. Yet, since judging and classifying patients with MM in a VTE risk group is difficult,6 we recommend physicians to use the IMPEDE VTE score.