Chromosome 1 abnormalities and survival of patients with multiple myeloma in the era of novel agents
Chromosome 1 abnormalities and survival of patients with multiple myeloma in the era of novel agents
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DOI：
10.1182/bloodadvances.2019001425
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发表时间：
2020-05-26
期刊：
影响因子：
7.5
通讯作者：
Neparidze, Natalia
中科院分区：
文献类型：
--
作者：
Giri, Smith;Huntington, Scott F.;Neparidze, Natalia
1号染色体异常（C1 A）是多发性骨髓瘤（MM）患者中常见的遗传畸变。我们的目的是评估C1 A在美国MM患者当代队列中的意义。我们使用Flatiron Health数据库中的电子健康记录，选择2011年1月至2018年3月期间新诊断为MM的患者，这些患者在诊断后90天内使用荧光原位杂交进行检测。我们将患者的特征描述为有记录的C1 A或其他高危染色体异常（HRCA），如国际修订分期系统（R-ISS）定义的del（17 p），t（14;16），st和t（4;14）。我们使用Kaplan-Meier方法比较有或无C1 A患者的总生存期（OS），并使用分层对数秩检验（以HRCA作为分层变量）。我们使用考克斯比例风险回归模型比较OS，调整年龄、性别、分期、HRCA和一线治疗类型。在3578例合格患者中，844例（24%）记录了C1 A。与无C1 A的患者相比，C1 A患者更有可能患有更高的分期（R-ISS分期18% vs 12%）、HRCA（27% vs 14%）和接受蛋白酶体抑制剂和免疫调节剂联合治疗（41% vs 34%）。C1 A患者的中位OS较低（46.6 vs 70.1个月;对数秩P <0.001）。C1 A与OS恶化独立相关（校正的风险比，1.42; 95%置信区间，1.19-2.69; P <0.001），年龄较大、R-ISS分期较高、HRCA和免疫球蛋白A同种型也是如此。C1 A与较差OS相关，独立于其他HRCA，尽管更多地使用新疗法。测试高危MM的新疗法的临床试验应纳入C1 A患者。
Chromosome 1 abnormalities (C1As) are common genetic aberrations among patients with multiple myeloma (MM). We aimed to evaluate the significance of C1As among a contemporary cohort of patients with MM in the United States. We used electronic health records from the Flatiron Health database to select patients newly diagnosed with MM from January 2011 to March 2018 who were tested using fluorescence in situ hybridization within 90 days of diagnosis. We characterized patients as having documented C1As or other high-risk chromosomal abnormalities (HRCAs) as defined by the Revised-International Staging System (R-ISS) such as del(17p), t(14;16), st and t(4;14). We used Kaplan-Meier methods to compare overall survival (OS) of patients with or without C1As and stratified log-rank tests (with the presence of HRCAs as a stratifying variable). We used Cox proportional hazards regression models to compare OS, adjusting for age, sex, stage, HRCAs, and type of first-line therapy. Of 3578 eligible patients, 844 (24%) had documented C1As. Compared with patients without C1As, patients with C1As were more likely to have higher stage (R-ISS stage 18% vs 12%), to have HRCAs (27% vs 14%), and to receive combinations of proteasome inhibitors and immunomodulatory agents (41% vs 34%). Median OS was lower for patients with C1As (46.6 vs 70.1 months; log-rank P < .001). C1As were independently associated with worse OS (adjusted hazard ratio, 1.42; 95% confidence interval, 1.19-2.69; P < .001), as were older age, higher R-ISS stage, HRCAs, and immunoglobulin A isotype. C1As were associated with inferior OS, independent of other HRCAs, despite greater use of novel therapies. Clinical trials testing newer therapies for high-risk MM should incorporate patients with C1As.