BACKGROUND Thromboprophylaxis is routinely used with lenalidomide-based regimens in multiple myeloma because of a substantial risk of venous thromboembolism (VTE). However, little is known about the incidence of VTE with contemporary lenalidomide-based regimens. The objective of the current study was to estimate the incidence of VTE despite thromboprophylaxis with currently used lenalidomide-based regimens in patients with myeloma. METHODS The Ovid MEDLINE, Embase, and Cochrane databases were queried from study inception to January 2019 for keywords to cover the following concepts: "lenalidomide," "venous thromboembolism," and "multiple myeloma." Phase 1, 2, and 3 clinical trials evaluating lenalidomide-based regimens with thromboprophylaxis were included. The pooled incidence rate of VTE was estimated using a random-effects model. RESULTS The search generated 1372 citations, with 51 clinical trials and 9069 patients included for analysis. The most common thromboprophylaxis agents were aspirin, low-molecular-weight heparin or warfarin, administered either per risk-stratification or at investigators' discretion. The pooled incidence of VTE in trials of patients who had newly diagnosed and relapsed/refractory myeloma was 6.2% (95% CI, 5.4%-7.1%) over median treatment durations ranging from 2 to 34 cycles, which translated into 1.2 VTE events per 100 patient-cycles (95% CI, 0.9-1.7 VTE events per 100 patient-cycles). Among contemporary regimens, the risk of VTE was low with combined lenalidomide and low-dose dexamethasone (0.2 [95% CI, 0.1-0.6] events/100 patient-cycles) and lenalidomide maintenance (0.0 [95% CI, 0.0-0.7] events per 100 patient-cycles). VTE risk was higher with combined lenalidomide and low-dose dexamethasone plus proteasome inhibitors (1.3 [95% CI, 0.7-2.3] events per 100 patient-cycles). CONCLUSIONS Despite adequate thromboprophylaxis, lenalidomide-based regimens have a substantial risk of VTE in controlled clinical trial settings. Further studies are needed on new thromboprophylaxis strategies with regimens that have a high VTE risk.

中文翻译：

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尽管有预防性治疗多发性骨髓瘤，但以来那度胺为基础的当代治疗方案仍有静脉血栓栓塞风险：系统评价和荟萃分析。

背景技术由于静脉血栓栓塞（VTE）的巨大风险，血栓预防通常与基于来那度胺的方案一起用于多发性骨髓瘤。然而，关于基于来那度胺的现代疗法的VTE发生率知之甚少。本研究的目的是评估骨髓瘤患者目前使用来那度胺为基础的方案尽管进行了预防血栓预防的VTE发生率。方法从研究开始到2019年1月，查询Ovid MEDLINE，Embase和Cochrane数据库的关键词，以涵盖以下概念：“来那度胺”，“静脉血栓栓塞”和“多发性骨髓瘤”。包括评估基于来那度胺的血栓预防方案的1、2和3期临床试验。使用随机效应模型估计VTE的合并发生率。结果搜索获得1372次引用，其中51项临床试验和9069例患者被纳入分析。最常见的血栓预防剂是阿司匹林，低分子量肝素或华法林，可根据风险分层或由研究者酌情决定使用。在2到34个周期的中位治疗期间，新诊断和复发/难治性骨髓瘤患者的VTE合并发生率为6.2％（95％CI，5.4％-7.1％），这转化为每个患者1.2 VTE事件100个患者周期（95％CI，每100个患者周期0.9-1.7 VTE事件）。在当代治疗方案中，来那度胺和小剂量地塞米松联合用药发生VTE的风险较低（0.2 [95％CI，0.1-0。6]事件/ 100个患者周期）和来那度胺维持（每100个患者周期0.0 [95％CI，0.0-0.7]个事件）。来那度胺和低剂量地塞米松联合蛋白酶体抑制剂的VTE风险更高（每100个患者周期1.3个事件[95％CI，0.7-2.3]事件）。结论尽管有足够的血栓预防措施，但基于来那度胺的治疗方案在受控的临床试验环境中仍存在很大的VTE风险。需要对具有高VTE风险的方案的新的血栓预防策略进行进一步研究。在控制性临床试验中，来那度胺为基础的治疗方案存在大量VTE风险。需要对具有高VTE风险的方案的新的血栓预防策略进行进一步研究。在控制性临床试验中，来那度胺为基础的治疗方案存在大量VTE风险。需要对具有高VTE风险的方案的新的血栓预防策略进行进一步研究。