Prospective Study of Cardiac Events During Proteasome Inhibitor Therapy for Relapsed Multiple Myeloma
Prospective Study of Cardiac Events During Proteasome Inhibitor Therapy for Relapsed Multiple Myeloma
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DOI：
10.1200/jco.19.00231
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发表时间：
2019-08-01
影响因子：
45.3
通讯作者：
Lenihan, Daniel
中科院分区：
文献类型：
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作者：
Cornell, Robert F.;Ky, Bonnie;Lenihan, Daniel
目的蛋白酶体抑制剂 (PI) 治疗期间可能会发生心血管不良事件 (CVAE)。我们进行了一项前瞻性、观察性、多机构研究，以确定接受 PI 治疗的多发性骨髓瘤 (MM) 患者的危险因素和结果。 患者和方法 开始基于卡非佐米或硼替佐米治疗的复发性 MM 患者接受基线评估，并在 6 个月内定期进行重复评估，包括心脏生物标志物（肌钙蛋白 I 或 T、脑钠尿肽 [BNP] 和 N 末端） proBNP）、心电图和超声心动图。对 CVAE 的发展进行了超过 18 个月的监测。 结果 在 95 名入组患者中，65 名接受卡非佐米，30 名接受硼替佐米，中位随访时间为 25 个月。发生了 64 起 CVAE，其中 55% 的严重程度为 3 级或以上。接受卡非佐米治疗的患者中有 51% 发生了 CVAE，而接受硼替佐米治疗的患者中有 17% 发生了 CVAE (P = .002)。从治疗开始到首次 CVAE 的中位时间为 31 天，86% 发生在前 3 个月内。接受基于卡非佐米治疗且基线 BNP 水平高于 100 pg/mL 或 N 末端 proBNP 水平高于 125 pg/mL 的患者发生 CVAE 的风险增加（比值比，10.8；P < .001）。卡非佐米治疗第一个周期中期出现的钠尿肽升高与 CVAE 风险显着升高相关（比值比，36.0；P < .001）。经历 CVAE 的患者无进展生存期 (对数秩 P = .01) 和总生存期 (对数秩 P < .001) 较差。 89% 的患者安全地恢复了 PI 治疗，尽管 41% 的患者需要对化疗进行修改。 结论 在复发 MM 的 PI 治疗期间，CVAE 很常见，尤其是卡非佐米，特别是在治疗的前 3 个月内。 CVAE 与较差的总体结果相关，但通常不需要停止治疗。利尿钠肽对 CVAE 有高度预测作用；然而，在统一纳入接受卡非佐米患者的常规管理之前，有必要验证这一发现。
PURPOSECardiovascular adverse events (CVAEs) can occur during proteasome inhibitor (PI) therapy. We conducted a prospective, observational, multi-institutional study to define risk factors and outcomes in patients with multiple myeloma (MM) receiving PIs.PATIENTS AND METHODSPatients with relapsed MM initiating carfilzomib- or bortezomib-based therapy underwent baseline assessments and repeated assessments at regular intervals over 6 months, including cardiac biomarkers (troponin I or T, brain natriuretic peptide [BNP], and N-terminal proBNP), ECG, and echocardiography. Monitoring occurred over 18 months for development of CVAEs.RESULTSOf 95 patients enrolled, 65 received carfilzomib and 30 received bortezomib, with median 25 months of follow-up. Sixty-four CVAEs occurred, with 55% grade 3 or greater in severity. CVAEs occurred in 51% of patients treated with carfilzomib and 17% of those treated with bortezomib (P = .002). Median time to first CVAE from treatment start was 31 days, and 86% occurred within the first 3 months. Patients receiving carfilzomib-based therapy with a baseline elevated BNP level higher than 100 pg/mL or N-terminal proBNP level higher than 125 pg/mL had increased risk for CVAE (odds ratio, 10.8; P < .001). Elevated natriuretic peptides occurring mid-first cycle of treatment with carfilzomib were associated with a substantially higher risk of CVAEs (odds ratio, 36.0; P < .001). Patients who experienced a CVAE had inferior progression-free survival (log-rank P = .01) and overall survival (log-rank P < .001). PI therapy was safely resumed in 89% of patients, although 41% required chemotherapy modifications.CONCLUSIONCVAEs are common during PI therapy for relapsed MM, especially with carfilzomib, particularly within the first 3 months of therapy. CVAEs were associated with worse overall outcomes, but usually, discontinuation of therapy was not required. Natriuretic peptides were highly predictive of CVAEs; however, validation of this finding is necessary before uniform incorporation into the routine management of patients receiving carfilzomib.