Çağlayan Çağlar, Terawaki Hiromi, Ayer Turgay, Goldstein Jordan S, Rai Ashish, Chen Qiushi, Flowers Christopher
H. Milton Stewart School of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, GA.
Winship Cancer Institute of Emory University, Atlanta, GA.
Clin Lymphoma Myeloma Leuk. 2019 May;19(5):300-309.e5. doi: 10.1016/j.clml.2018.12.019. Epub 2019 Jan 3.
Disease progression within < 2 years of initial chemoimmunotherapy and patient age > 60 years have been associated with poor overall survival (OS) in follicular lymphoma (FL). No standard treatment exists for these high-risk patients, and the effectiveness of sequential therapies remains unclear.
We studied the course of FL with first-, second-, and third-line treatment. Using large population-based data, we identified 5234 patients with FL diagnosed in 2000 to 2009. Of these patients, 71% had received second-line therapy < 2 years, and 29% had received no therapy after first-line therapy, with a median OS of < 3 years. Treatment included rituximab, R-CVP (rituximab, cyclophosphamide, vincristine), R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine), R-Other (other rituximab-containing), and other regimens. The Aalen-Johansen estimator and Cox proportional hazards models were used to quantify the outcomes and assess the effects of the clinical and sociodemographic factors.
R-CHOP demonstrated the most favorable 5-year OS among first- (71%), second- (55%), and third-line (61%) therapies. First-line R-CHOP improved OS (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.50-0.64) and reduced the mortality risks after first-line (HR, 0.60; 95% CI, 0.47-0.77), second-line (HR, 0.40; 95% CI, 0.29-0.53), and third-line (HR, 0.63; 95% CI, 0.53-0.76) treatments. B-symptoms, being married, and histologic grade 1/2 were associated with the use of earlier second-line therapy. Early progression from second- to third-line therapy was associated with poor OS. The repeated use of R-CHOP or R-CVP as first- and second-line treatment yielded high 2-year mortality rates (R-CHOP + R-CHOP, 17.3%; R-CVP + R-CVP, 21.1%).
Our multistate approach assessed the effect of sequential therapy on the immediate and subsequent treatment-line outcomes. We found that R-CHOP in any line improved OS for patients with high-risk FL.
在滤泡性淋巴瘤(FL)中,初始化疗免疫治疗后<2年疾病进展以及患者年龄>60岁与总生存期(OS)较差相关。对于这些高危患者不存在标准治疗方案,序贯治疗的有效性仍不明确。
我们研究了FL一线、二线和三线治疗的过程。利用基于人群的大型数据,我们确定了2000年至2009年诊断的5234例FL患者。在这些患者中,71%在<2年时接受了二线治疗,29%在一线治疗后未接受治疗,中位OS<3年。治疗包括利妥昔单抗、R-CVP(利妥昔单抗、环磷酰胺、长春新碱)、R-CHOP(利妥昔单抗、环磷酰胺、羟基柔红霉素、长春新碱)、R-其他(其他含利妥昔单抗方案)以及其他方案。使用Aalen-Johansen估计器和Cox比例风险模型来量化结局并评估临床和社会人口统计学因素的影响。
在一线(71%)、二线(55%)和三线(61%)治疗中,R-CHOP显示出最有利的5年OS。一线使用R-CHOP改善了OS(风险比[HR],0.57;95%置信区间[CI],0.50-0.64),并降低了一线(HR,0.60;95%CI,0.47-0.77)、二线(HR,0.40;95%CI,0.29-0.53)和三线(HR,0.63;95%CI,0.53-0.76)治疗后的死亡风险。B症状、已婚以及组织学1/2级与较早使用二线治疗相关。从二线到三线治疗的早期进展与较差的OS相关。一线和二线重复使用R-CHOP或R-CVP导致2年死亡率较高(R-CHOP+R-CHOP,17.3%;R-CVP+R-CVP,21.1%)。
我们的多状态方法评估了序贯治疗对直接和后续治疗线结局的影响。我们发现,任何治疗线使用R-CHOP均可改善高危FL患者的OS。