Abstract
Multiple myeloma (MM) is associated to an increased incidence of venous thromboembolism (VTE). IMPEDE-VTE score constitutes a valuable risk assessment tool for VTE prediction in first-line MM patients. Nevertheless, refinement of the primary thromboprophylaxis category of this score (which pools aspirin and heparin) seems desirable. To investigate the role of the type of thromboprophylaxis, within IMPEDE-VTE score, for VTE prediction in MM patients. Retrospective analysis of a single-center cohort of 438 MM patients receiving first-line antimyeloma treatment (1991–2020). IMPEDE-VTE score was calculated. Primary thromboprophylaxis was additionally stratified into aspirin- and heparin-based regimen subgroups. VTE risk was analyzed by Cox regression. Median follow-up during first-line antimyeloma treatment was 6.0 months (IQR 4.1–9.0 months). Twenty-three patients developed VTE (5.3%, 95%CI 3.4–7.8%). IMPEDE-VTE score showed a notable predictive value (area under the ROC curve: 0.70, 95%CI 0.60–0.80). Cox analysis confirmed that 1-point increase in the score resulted in a 1.3-fold increase in VTE risk (HR 1.30, 95%CI 1.13–1.53, p < 0.001). In the multivariable analysis, the type of primary thromboprophylaxis (heparin versus aspirin) was an independent predictive factor (HR 0.15, 95% CI 0.05–0.47, p = 0.001). The combined model showed a higher goodness-of-fit (Akaike Information Criterion [AIC]: 99) than IMPEDE-VTE separately (AIC:235). Our analysis contributes to the external validation of IMPEDE-VTE score for the prediction of VTE in MM. But more interestingly, our results demonstrate that among those patients receiving thromboprophylaxis, the type of regimen (heparin versus aspirin) adds independent predictive value and should be explored for a more accurate risk assessment.
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Derived data supporting the findings of this study are available from the corresponding author CBP on request.
References
Srkalovic G, Cameron MG, Rybicki L et al (2004) Monoclonal gammopathy of undetermined significance and multiple myeloma are associated with an increased incidence of venothromboembolic disease. Cancer 101:558–566. https://doi.org/10.1002/cncr.20405
Bick RL (2003) Cancer-associated thrombosis. N Engl J Med 349:109–111. https://doi.org/10.1056/NEJMp030086
Rajkumar SV, Blood E, Vesole D et al (2006) Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: a clinical trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol 24:431–436. https://doi.org/10.1200/JCO.2005.03.0221
Cavo M, Zamagni E, Tosi P et al (2004) First-line therapy with thalidomide and dexamethasone in preparation for autologous stem cell transplantation for multiple myeloma. Haematologica 89:826–831
Raghupathy R, Ayyappan S, Prabhakar D et al (2017) Retrospective study of the incidence and patterns of arterial and venous thrombosis in Chinese versus African American patients with multiple myeloma. Br J Haematol 176:315–317. https://doi.org/10.1111/bjh.13942
Zonder JA, Barlogie B, Durie BGM et al (2006) Thrombotic complications in patients with newly diagnosed multiple myeloma treated with lenalidomide and dexamethasone: benefit of aspirin prophylaxis. Blood 108:403; author reply 404
Palumbo A, Rajkumar SV, Dimopoulos MA et al (2008) Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia 22:414–423. https://doi.org/10.1038/sj.leu.2405062
Crowley MP, Eustace JA, O’Shea SI, Gilligan OM (2014) Venous thromboembolism in patients with myeloma: incidence and risk factors in a “real-world” population. Clin Appl Thromb 20:600–606. https://doi.org/10.1177/1076029614521280
Sanfilippo KM, Luo S, Wang T-F et al (2019) Predicting venous thromboembolism in multiple myeloma: development and validation of the IMPEDE VTE score. Am J Hematol 94:1176–1184. https://doi.org/10.1002/ajh.25603
Chalayer E, Teste A, Guyotat D et al (2020) Predicting the risk of venous thromboembolism in newly diagnosed myeloma with immunomodulatory drugs: external validation of the IMPEDE VTE score. Am J Hematol 95:E18–E20
IMWG (2010) IMWG guidelines for the prevention of thalidomide and lenalidomide-associated thrombosis in myeloma. IMWG, North Hollywood, CA, USA. Available from https://www.myeloma.org/resource-library/imwg-guidelines-prevention-thalidomide-lenalidomide-associated-thrombosis-myeloma
Streiff MB, Holmstrom B, Angelini D et al (2018) NCCN guidelines insights: cancer-associated venous thromboembolic disease, version 2.2018. J Natl Compr Canc Netw 16:1289–1303. https://doi.org/10.6004/jnccn.2018.0084
Fotiou D, Gavriatopoulou M, Terpos E (2020) Multiple myeloma and thrombosis: prophylaxis and risk prediction tools. Cancers (Basel). https://doi.org/10.3390/cancers12010191
McElreath R (2020) Statistical rethinking. Chapman and Hall/CRC Press, Boca Raton, p 239
National Statistics Institute of Spain (2020) Foreign population by sex, provinces and nationality in Spain. https://www.ine.es/jaxi/Tabla.htm?path=/t20/e245/p04/provi/l0/&file=0ccaa002.px
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C. Bravo-Perez is the recipient of a Río Hortega contract for medical research investigator training from Instituto de Salud Carlos III (CM20/00094).
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MDG-M, AJ and FdA enrolled study cohort patients. CB-P, MF-C and ES-E performed and/or supervised data extraction. CB-P, MF-C, EG-T and MS analyzed data, made figures and wrote the paper. VV, VR and FdA supervised the work, discussed the results and wrote the paper. All authors revised the manuscript.
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All included subjects gave their informed consent for their inclusion in this cohort, which was approved by the Ethics Committee of Morales Meseguer Hospital, and performed in accordance with the 1964 Declaration of Helsinki and their later amendments.
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Bravo-Perez, C., Fernández-Caballero, M., Soler-Espejo, E. et al. Heparin versus aspirin thromboprophylaxis adds independent value to IMPEDE-VTE score for venous thrombosis prediction in multiple myeloma. J Thromb Thrombolysis 52, 848–853 (2021). https://doi.org/10.1007/s11239-021-02407-5
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DOI: https://doi.org/10.1007/s11239-021-02407-5