■在弥漫性大B细胞淋巴瘤(DLBCL)的老年患者中,需要明确基于简化的老年评估来预测治疗相关毒性和生存率的最佳风险分层。
■这项多中心前瞻性队列研究纳入了2015年9月至2018年4月期间新诊断的DLBCL患者(≥65岁)。在基线时使用日常生活活动(ADL)进行简化的老年评估,器乐ADL(IADL),和Charlson的合并症指数(CCI)。主要终点是无事件生存期(EFS)。
■该研究包括249名患者,中位年龄为74岁(范围,65-88),女性125人(50.2%)。在多变量Cox分析中,ADL,IADL,CCI和年龄是EFS的独立因素;得出综合老年评分,并将患者分为三个老年类别:适合(n=162,65.1%),中等拟合(n=25,10.0%),体弱多病(n=62,24.9%)。建立的老年模型与EFS显著相关(拟合与中等配合,HR2.61,p<0.001;拟合与脆弱,HR4.61,p<0.001),并且优于单独或组合的每个协变量。在87名中等健康或虚弱的患者中,相对阿霉素剂量强度(RDDI)≥62.4%与EFS恶化显著相关(HR,2.15,95%CI1.30-3.53,p=0.002)。它与≥3级症状性非血液学毒性的发生率较高有关(63.2%vs.27.8%,p<0.001)和早期治疗停药(34.5%vs.8.0%,p<0.001)RDDI≥62.4%的患者比RDDI<62.4%的患者。
■该模型整合了简化的老年评估,可以对患有DLBCL的老年患者进行风险分层,并确定那些对标准剂量强度化学免疫疗法非常脆弱的患者。
OBJECTIVE: Optimal risk stratification based on simplified geriatric assessment to predict treatment-related toxicity and survival needs to be clarified in older patients with diffuse large B-cell lymphoma (DLBCL).
METHODS: This multicenter prospective cohort study enrolled newly diagnosed patients with DLBCL (≥ 65 yr) between September 2015 and April 2018. A simplified geriatric assessment was performed at baseline using Activities of Daily Living (ADL), Instrumental ADL (IADL), and Charlson\'s Comorbidity Index (CCI). The primary endpoint was event-free survival (EFS).
RESULTS: The study included 249 patients, the median age was 74 years (range, 65-88), and 125 (50.2%) were female. In multivariable Cox analysis, ADL, IADL, CCI, and age were independent factors for EFS; an integrated geriatric score was derived and the patients stratified into three geriatric categories: fit (n = 162, 65.1%), intermediate-fit (n = 25, 10.0%), and frail (n = 62, 24.9%). The established geriatric model was significantly associated with EFS (fit vs. intermediate-fit, HR 2.61, p < 0.001; fit vs. frail, HR 4.61, p < 0.001) and outperformed each covariate alone or in combination. In 87 intermediate-fit or frail patients, the relative doxorubicin dose intensity (RDDI) ≥ 62.4% was significantly associated with worse EFS (HR, 2.15, 95% CI 1.30-3.53, p = 0.002). It was related with a higher incidence of grade ≥ 3 symptomatic non-hematologic toxicities (63.2% vs. 27.8%, p < 0.001) and earlier treatment discontinuation (34.5% vs. 8.0%, p < 0.001) in patients with RDDI ≥ 62.4% than in those with RDDI < 62.4%.
CONCLUSIONS: This model integrating simplified geriatric assessment can risk-stratify older patients with DLBCL and identify those who are highly vulnerable to standard dose-intensity chemoimmunotherapy.