Assessing Venous Thromboembolism Risk in Patients with Multiple Myeloma: A Nationwide Population-Based Study in Taiwan

Background. Venous thromboembolism (VTE) represents a significant disease- and treatment-related complication in multiple myeloma (MM). The studies of VTE in Asian myeloma patients are limited due to the low incidence of VTE in the Asian population. We conducted a comprehensive nationwide population-based study to elucidate the incidence and risk factors of VTE among MM patients in Taiwan.

Material and methods. We consecutively enrolled all patients newly diagnosed with MM in Taiwan from 2000 to 2021. The patients aged less than 18 or those without baseline data were excluded. The primary endpoint was the occurrence of VTE, including deep venous thrombosis and pulmonary embolism. Hazard ratios (HRs) for VTE risk in MM patients relative to an age- and sex-matched cohort were computed using Cox proportional regression analysis. Therapeutic agents were integrated into the Cox models as time-dependent covariates to mitigate immortal time bias. Multivariable Cox proportional hazards models were employed to identify independent predictors of VTE.

Results. This study encompassed 10,865 patients with MM and the same matched individuals, with a median age of 68 years (interquartile range 60–77). Among the MM patients, 57.0% were male. The most common comorbidities were dyslipidemia (76.3%), hypertension (67.5%), chronic kidney disease (45.2%), coronary artery disease (CAD; 44.0%), and chronic obstructive pulmonary disease (COPD; 39.3%). One hundred sixty-four VTE events developed among the MM patients, with a follow-up of 31,078.0 person-years. The VTE incidence was 14.5 times higher in the MM cohort than in the matched cohort (5.3 vs. 0.4 cases per 1,000 person-years; p < 0.001). Univariate analysis identified several significant predictors of VTE, including CAD (HR 1.81), COPD (HR 1.37), cerebrovascular accident (HR 1.60), heart failure (HF; HR 1.47), hypertension (HR 1.85), prior VTE (HR 24.29), age ≥ 65 years (HR 1.54), male gender (HR 0.75), and immunomodulatory drug (IMiD) therapy (HR 1.70). The multivariable Cox proportional hazards models highlighted CAD (adjusted HR 1.43; 95% CI 1.01–2.01, p = 0.042), prior VTE (adjusted HR 21.12; 95% CI 11.30–39.47, p < 0.001), and IMiD therapy (adjusted HR 1.68; 95% CI 1.19–2.37, p = 0.003) as independent risk factors for VTE in MM patients. Further analysis of IMiD therapy revealed adjusted HRs of 1.53 (95% CI 1.09–2.17; p = 0.015) for thalidomide and 2.05 (95% CI 1.34–3.13; p = 0.001) for lenalidomide.

Conclusion. This study substantiates the elevated risk of VTE in MM patients compared to an age- and sex-matched cohort. CAD, prior VTE, and immunomodulatory drug treatment are linked to an increased VTE risk in this population. These findings underscore the importance of implementing targeted preventive strategies for this high-risk group.