多发性骨髓瘤的抗血栓形成药物应用、不良事件及其与治疗结局的关联：三项临床试验的汇总分析
Antithrombotic utilization, adverse events, and associations with treatment outcomes in multiple myeloma: pooled analysis of three clinical trials.
作者信息
Almansour Sara A, Alqudah Mohammad A Y, Abuhelwa Ziad, Al-Shamsi Humaid O, Alhuraiji Ahmad, Semreen Mohammad H, Bustanji Yasser, Alzoubi Karem H, Modi Natansh D, Mckinnon Ross A, Sorich Michael J, Hopkins Ashley M, Abuhelwa Ahmad Y
机构信息
Department of Pharmacy Practice and Pharmacotherapeutics, University of Sharjah, Sharjah, United Arab Emirates.
Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan.
出版信息
Ther Adv Med Oncol. 2024 Sep 2;16:17588359241275387. doi: 10.1177/17588359241275387. eCollection 2024.
BACKGROUND
Patients with multiple myeloma (MM) are at risk of venous thromboembolism (VTE), worsened by immunomodulatory drugs. Although antithrombotics are recommended for prophylaxis, existing guidelines are suboptimal and treatment outcomes remain unclear.
OBJECTIVES
This study aimed to investigate adverse events, antithrombotic utilization, and their associations with survival outcomes in patients with MM initiating multi-drug immunomodulatory combinations.
DESIGN
A posthoc analysis of individual-participant level data (IPD).
METHODS
IPD from three daratumumab clinical trials (MAIA, POLLUX, and CASTOR) were pooled. Adverse events incidence and antithrombotic utilization were assessed. Logistic and Cox regression were utilized to examine associations between antithrombotics use with adverse events and survival outcomes at the baseline and 6-month landmark.
RESULTS
Among 1804 patients, VTE occurred in 10%, bleeding in 14%, ischemic heart disease in 4%, and stroke in 2%. Patients with these adverse events demonstrated elevated rates of any grade ⩾3 events. Antiplatelet (primarily aspirin) and anticoagulant (primarily LMWH and direct oral anticoagulants) prescriptions have seen an increase from baseline (25% and 14%, respectively) to 6 months (35% and 31%). The primary indication for their use was prophylaxis. Anticoagulant use within 6 months was associated with reduced VTE (OR (95% CI) = 0.45 (0.26-0.77), = 0.004), while antiplatelet use showed no associations with any evaluated adverse events. Antithrombotics and survival outcomes had no significant associations.
CONCLUSION
This study underscores the complexities of antithrombotic therapy and adverse events in MM and highlights the need for vigilant and proactive management due to increased grade ⩾3 adverse events. While anticoagulant use was associated with reduced VTE risk, further research is needed to optimize thromboprophylaxis guidelines and explore antithrombotic efficacy and safety in patients with MM.
TRIAL REGISTRATION
MAIA (NCT02252172), POLLUX (NCT02076009), CASTOR (NCT02136134).
背景
多发性骨髓瘤（MM）患者存在静脉血栓栓塞（VTE）风险，免疫调节药物会使其风险加剧。尽管推荐使用抗栓药物进行预防，但现有指南并不理想，治疗结果仍不明确。
目的
本研究旨在调查启动多药免疫调节联合治疗的MM患者的不良事件、抗栓药物使用情况及其与生存结果的关联。
设计
对个体参与者水平数据（IPD）进行事后分析。
方法
汇总来自三项达雷妥尤单抗临床试验（MAIA、POLLUX和CASTOR）的IPD。评估不良事件发生率和抗栓药物使用情况。采用逻辑回归和Cox回归分析基线和6个月时抗栓药物使用与不良事件及生存结果之间的关联。
结果
在1804例患者中，VTE发生率为10%，出血发生率为14%，缺血性心脏病发生率为4%，中风发生率为2%。发生这些不良事件的患者⩾3级事件的发生率有所升高。抗血小板药物（主要是阿司匹林）和抗凝药物（主要是低分子肝素和直接口服抗凝剂）的处方从基线时（分别为25%和14%）增加到6个月时（分别为35%和31%）。使用这些药物的主要指征是预防。6个月内使用抗凝药物与VTE风险降低相关（比值比（95%置信区间）=0.45（0.26 - 0.77），P = 0.004），而使用抗血小板药物与任何评估的不良事件均无关联。抗栓药物与生存结果无显著关联。
结论
本研究强调了MM抗栓治疗和不良事件的复杂性，并凸显了因⩾3级不良事件增加而需要进行警惕和积极管理的必要性。虽然使用抗凝药物与降低VTE风险相关，但仍需进一步研究以优化血栓预防指南，并探索MM患者抗栓治疗的疗效和安全性。
试验注册
MAIA（NCT02252172）、POLLUX（NCT02076009）、CASTOR（NCT02136134）。
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