Tang Wenjiao, Yang Jinrong, Li Yan, Zhang Li, Li He, Wang Jie, Liao Yi, Zhang Chunlan, Qu Ying, Zheng Yuhuan, Niu Ting
Department of Hematology, Institute of Hematology, West China Hospital Sichuan University, Chengdu, China.
Front Pharmacol. 2023 Jan 12;14:979111. doi: 10.3389/fphar.2023.979111. eCollection 2023.
For multiple myeloma (MM), the proportions of patients reaching the subsequent line of therapy (LOT) decline gradually and real-world data describing the attrition rates of LOT in Chinese MM were limited. Herein, we investigated the attrition rates by subsequent LOTs and their relevant risk factors in MM patients in China. MM patients who had been hospitalized and received at least one LOT from January 2008 to August 2019 in West China Hospital Sichuan University were retrospectively recruited. Demographic and clinical characteristic data were obtained from the "HemaTank" Chinese Multiple Myeloma Database. The Cox proportional hazards regression model was applied to analyze the risk factors of frontline treatment attrition. A total of 1,255 newly diagnosed MM were enrolled, with 573 (45.7%) patients receiving only one LOT and 682 (54.3%) patients receiving more than one LOT. Thalidomide with dexamethasone/prednisone was the most common frontline treatment before 2017, while bortezomib-based regimens constituted the majority of frontline treatment in 2017 and beyond. The attrition rates from the first to the fifth LOT exhibited a gradual upward trend (45.7%, 48.7%, 58.9% and 62.5%, respectively). Meanwhile, 54.3%, 27.9%, 11.5%, and 4.3% of all the enrolled MM patients received a second, third, fourth and fifth LOT. MM who underwent autologous stem cell transplantation (ASCT) showed lower attrition rates across all LOTs (range 12%-56.8%) than MM without ASCT (range 49.1%-64.5%). The multivariate Cox regression model revealed that ISS stage III (HR 2.07, < .001), elevated LDH (HR 1.47, = .006), and comorbidities such as amyloidosis (HR 1.63, = 0 .01), hepatic disease (HR 1.36, = .022), pulmonary disease (HR 1.38, = .022), and cardiac disease (HR 1.62, = .004) were independent risk factors for MM patients attritted from the frontline treatment. In this study, the attrition rates were generally high and increased gradually across all LOTs. Nearly half of MM patients received only one LOT, and higher tumor burden and more comorbidities may be associated with fewer subsequent LOTs. The high attrition rates highlight the importance of applying the most optimal frontline treatment regimen rather than salvaging subsequent LOTs.
对于多发性骨髓瘤（MM），进入后续治疗线（LOT）的患者比例逐渐下降，而描述中国MM患者LOT损耗率的真实世界数据有限。在此，我们调查了中国MM患者后续LOT的损耗率及其相关危险因素。回顾性招募了2008年1月至2019年8月在四川大学华西医院住院并接受至少一次LOT的MM患者。人口统计学和临床特征数据来自“血液库”中国多发性骨髓瘤数据库。应用Cox比例风险回归模型分析一线治疗损耗的危险因素。共纳入1255例新诊断的MM患者，其中573例（45.7%）患者仅接受一次LOT，682例（54.3%）患者接受不止一次LOT。沙利度胺联合地塞米松/泼尼松是2017年前最常见的一线治疗方案，而2017年及以后以硼替佐米为基础的方案构成了一线治疗的大部分。从第一LOT到第五LOT的损耗率呈逐渐上升趋势（分别为45.7%、48.7%、58.9%和62.5%）。同时，所有纳入的MM患者中，54.3%、27.9%、11.5%和4.3%接受了第二、第三、第四和第五LOT。接受自体干细胞移植（ASCT）的MM患者在所有LOT中的损耗率（范围为12%-56.8%）低于未接受ASCT的MM患者（范围为49.1%-64.5%）。多变量Cox回归模型显示，国际分期系统（ISS）III期（风险比[HR]2.07，P<0.001）、乳酸脱氢酶（LDH）升高（HR 1.47，P = 0.006）以及淀粉样变性（HR 1.63，P = 0.01）、肝病（HR 1.36，P = 0.022）、肺病（HR 1.38，P = 0.022）和心脏病（HR 1.62，P = 0.004）等合并症是MM患者一线治疗损耗的独立危险因素。在本研究中，损耗率总体较高，且在所有LOT中逐渐增加。近一半的MM患者仅接受一次LOT，较高的肿瘤负荷和更多的合并症可能与较少的后续LOT相关。高损耗率凸显了应用最优化一线治疗方案而非挽救后续LOT的重要性。
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