基于老年评估的弥漫性大B细胞淋巴瘤老年患者治疗：二十年临床经验的结果

摘要(中文译文)

背景：由于利妥昔单抗、环磷酰胺、阿霉素、长春新碱和泼尼松龙（R-CHOP）对化疗的适应性和耐受性存在异质性，治疗老年弥漫性大B细胞淋巴瘤（DLBCL）患者具有挑战性。因此，我们之前为这一人群建立了年龄、共病和白蛋白（ACA）指数，这是一项包括四个类别的老年评估。然而，它在治疗决策中的作用尚不清楚。方法：我们对患者进行了回顾性研究 ≥ 65 2015年至2022年期间接受R-CHOP治疗的DLBCL患者（ACA后队列），评估初始剂量强度（IDI）、相对剂量强度（RDI）和2年总生存期（OS）。在此期间，多学科肿瘤学团队根据ACA指数类别（优秀、良好、中等和较差）调整了细胞毒性药物的剂量强度。然后，我们将这些结果与2001年至2012年间接受R-CHOP治疗的患者的历史队列（ACA前队列）进行了比较，其中剂量强度由每位医生自行决定。倾向评分匹配（PSM）根据国际预后指数和ACA指数进行调整，用于平衡队列之间的基线特征。结果：在由135名中位年龄为76岁（范围：65-91岁）的ACA后患者组成的队列中，根据上述ACA类别，IDI、RDI和2年OS的中位数分别为97%、80%、70%和70%（p < 0.001);93%、78%、62%和59%（p < 0.001);96%、89%、66%和51%（p < 0.001),分别。PSM后，将ACA前后队列中的98名患者配对。尽管患者的人口统计数据均衡，但粒细胞集落刺激因子预防在ACA后组中更为常用（100%对49%，p < 0.001). 因此，ACA后组的IDI和RDI中位数较高（80%对68%，p < 0.001,77%对47%，p < 0.001,2年OS（81%对66%，p = 0.014). 结论：ACA指数可作为老年DLBCL患者个体化剂量强度调整的可行标准护理框架。尽管这种策略组织了治疗决策，但弱势患者的结果仍然明显较差，这突显了进一步优化治疗和新策略的必要性。

Abstract

BACKGROUND: Treating older patients with diffuse large B-cell lymphoma (DLBCL) is challenging due to heterogeneity in fitness and tolerance to chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). Thus, we previously established the Age, Comorbidity, and Albumin (ACA) index for this population, a geriatric assessment comprising four categories. However, its role in treatment decision-making remains unclear. METHODS: We conducted a retrospective study in patients ≥ 65 years old with DLBCL who were treated with R-CHOP between 2015 and 2022 (post-ACA cohort), evaluating initial dose intensity (IDI), relative dose intensity (RDI), and 2-year overall survival (OS). During this period, dose intensities of cytotoxic drugs were adjusted by the multidisciplinary oncology team according to the ACA index categories (Excellent, Good, Moderate, and Poor). Then, we compared these outcomes with a historical cohort of patients receiving R-CHOP between 2001 and 2012 (pre-ACA cohort), where the dose intensities were determined by each physician’s discretion. Propensity score matching (PSM), adjusted for the International Prognostic Index and the ACA index, was used to balance baseline characteristics between the cohorts. RESULTS: In the post-ACA cohort comprising 135 patients with a median age of 76 years (range: 65–91 years), the median IDI, median RDI, and 2-year OS according to the aforementioned ACA categories were 97%, 80%, 70%, and 70% (p < 0.001); 93%, 78%, 62%, and 59% (p < 0.001); and 96%, 89%, 66%, and 51% (p < 0.001), respectively. After PSM, 98 patients from the pre- and post-ACA cohorts were paired. Despite well-balanced patient demographics, granulocyte-colony stimulating factor prophylaxis was more commonly used in the post-ACA group (100% vs. 49%, p < 0.001). Consequently, the post-ACA group had higher median IDI and RDI (80% vs. 68%, p < 0.001, and 77% vs. 47%, p < 0.001, respectively) and better 2-year OS (81% vs. 66%, p = 0.014). CONCLUSIONS: The ACA index can serve as a feasible standard-of-care framework for individualized dose intensity adjustment in older patients with DLBCL. Although this strategy organizes treatment decision-making, vulnerable patients still exhibit significantly inferior outcomes, highlighting the need for further therapeutic optimization and novel strategies.

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