Antithrombotic utilization, adverse events, and associations with treatment outcomes in multiple myeloma: pooled analysis of three clinical trials.

IF 4.3 2区医学 Q2 ONCOLOGY Therapeutic Advances in Medical Oncology Pub Date : 2024-09-02 eCollection Date: 2024-01-01 DOI:10.1177/17588359241275387

Sara A Almansour, Mohammad A Y Alqudah, Ziad Abuhelwa, Humaid O Al-Shamsi, Ahmad Alhuraiji, Mohammad H Semreen, Yasser Bustanji, Karem H Alzoubi, Natansh D Modi, Ross A Mckinnon, Michael J Sorich, Ashley M Hopkins, Ahmad Y Abuhelwa

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Abstract

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), p = 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).

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多发性骨髓瘤患者抗血栓使用情况、不良事件及其与治疗结果的关系：三项临床试验的汇总分析。

背景：多发性骨髓瘤（MM）患者有静脉血栓栓塞症（VTE）的风险，免疫调节药物会加重这种风险。虽然建议使用抗血栓药物进行预防，但现有指南并不理想，治疗效果也不明确：本研究旨在调查开始使用多种药物免疫调节联合疗法的 MM 患者的不良事件、抗血栓药物使用情况及其与生存结果的关系：设计：对个体参与者水平数据（IPD）进行事后分析：汇总三项达拉单抗临床试验（MAIA、POLLUX和CASTOR）的IPD。评估了不良事件发生率和抗血栓药物使用情况。利用逻辑回归和 Cox 回归研究抗血栓药物的使用与不良事件以及基线和 6 个月生存结果之间的关系：在 1804 名患者中，10% 的患者发生了 VTE，14% 的患者发生了出血，4% 的患者发生了缺血性心脏病，2% 的患者发生了中风。发生这些不良事件的患者中，发生⩾3级不良事件的比例较高。抗血小板（主要是阿司匹林）和抗凝剂（主要是 LMWH 和直接口服抗凝剂）处方从基线（分别为 25% 和 14%）到 6 个月（分别为 35% 和 31%）期间有所增加。使用这些药物的主要适应症是预防。6 个月内使用抗凝剂与减少 VTE 相关（OR (95% CI) = 0.45 (0.26-0.77)，p = 0.004），而使用抗血小板与任何评估的不良事件均无关联。抗血栓药物与生存结果无明显关联：本研究强调了抗血栓治疗和MM不良事件的复杂性，并强调由于3级不良事件的增加，需要警惕和积极的管理。虽然抗凝剂的使用与VTE风险的降低有关，但仍需进一步研究以优化血栓预防指南，并探索MM患者的抗血栓疗效和安全性：MAIA（NCT02252172）、POLLUX（NCT02076009）、CASTOR（NCT02136134）。

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来源期刊

Therapeutic Advances in Medical Oncology ONCOLOGY-

CiteScore

8.20

自引率

2.00%

发文量

160

审稿时长

15 weeks

期刊介绍： Therapeutic Advances in Medical Oncology is an open access, peer-reviewed journal delivering the highest quality articles, reviews, and scholarly comment on pioneering efforts and innovative studies in the medical treatment of cancer. The journal has a strong clinical and pharmacological focus and is aimed at clinicians and researchers in medical oncology, providing a forum in print and online for publishing the highest quality articles in this area. This journal is a member of the Committee on Publication Ethics (COPE).