Risk of thromboembolism in patients with multiple myeloma treated with daratumumab: a systemic review and meta-analysis
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ORIGINAL ARTICLE
Risk of thromboembolism in patients with multiple myeloma treated with daratumumab: a systemic review and meta‑analysis Jiasheng Wang1 · Yeseong Kim1 Received: 27 June 2020 / Revised: 9 July 2020 / Accepted: 14 July 2020 © Japanese Society of Hematology 2020
Abstract Background Patients with multiple myeloma (MM) have increased risks of venous thromboembolism (VTE) and arterial thromboembolism (ATE). The risk of thrombosis differs among different treatment regimens. It is unknown if daratumumab could affect thrombosis risk. Methods A comprehensive search was conducted until April 2020. Events of VTE, including pulmonary embolism and deep venous thrombosis, as well as events of ATE, including acute ischemic stroke and myocardial infarction, were extracted from trials. In addition, events of thrombocytopenia and gastrointestinal (GI) bleeding were also extracted. Results Six trials were included in the meta-analysis. Daratumumab was associated with a lower risk of VTE compared with non-daratumumab regimen (Risk ratio [RR], 0.60; 95% confidence interval [CI], 0.40–0.91). The risk of ATE had no significant difference (RR, 0.80; 95% CI, 0.48–1.33). Daratumumab was also associated with a trend of higher risk of Grade 3/4 thrombocytopenia (RR, 1.14; 95% CI, 0.94–1.38), while the risk of GI bleeding was not significantly different (RR, 1.32; 95% CI, 0.38–4.65). Conclusion Daratumumab is associated with lower risk of VTE in clinical trials. Keywords Multiple myeloma · Daratumumab · Venous thromboembolism · Arterial thromboembolism
Background Cancer patients are known to have a higher incidence of thromboembolism than the general population. Patients with malignant hematologic diseases, in particular those with multiple myeloma (MM), are among the highest risk group [1, 2]. In a population study, the hazard ratio was 7.5 for venous thromboembolism (VTE) and 1.7 for arterial thromboembolism (ATE) in patients with MM, compared with their matched controls [3]. Studies have shown that the risk of thromboembolism in MM is modified by patient factors, disease status, as well as treatment regimen [4]. Indeed, in patients receiving immunomodulatory drugs (IMiDs) Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12185-020-02954-2) contains supplementary material, which is available to authorized users. * Jiasheng Wang [email protected] 1
Department of Internal Medicine, MetroHealth Medical Center, Case Western Reserve University, 2500 MetroHealth Dr, Cleveland, OH 44109, USA
containing regimen, the incidence of VTE could be as high as 20% [5]. Therefore, routine VTE prophylaxis is recommended for patients receiving IMiD-containing regimen [6]. Daratumumab, an anti-CD38 monoclonal antibody, is becoming the first-line treatment for relapsed/refractory MM, as well as newly diagnosed MM with high risk features. However, its association with thromboembolism has not been well studied. Given that CD38 plays a critical role in the procoagulant activity of p
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