Xu Tian-Yuan, Mu Rong-Ji, Zhang Hui-Lai, Xu Bing, Li Rong, Wang Nan, Sun Rui, Li Rui-Chi, Fu Di, Wang Xian-Huo, Li Zhi-Feng, Zhao Yan, Xu Peng-Peng, Cheng Shu, Wang Li, Tang Wei, Zheng Zhong, Zhao Wei-Li
Shanghai Institute of Hematology, State Key Laboratory of Medica Genomics, National Research Center for Translational Medicine at Shanghai Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China.
Clinical Research Institute Shanghai Jiao Tong University School of Medicine Shanghai China.
Hemasphere. 2025 May 7;9(5):e70141. doi: 10.1002/hem3.70141. eCollection 2025 May.
Follicular lymphoma (FL) patients with low tumor burden at diagnosis frequently undergo the watch-and-wait (W&W) strategy. The study aimed to facilitate risk assessment in predicting the time to lymphoma treatment (TLT) for W&W patients through an integrated analysis of clinical factors and genetic mutations. A retrospective study was conducted on 214 FL patients managed with W&W between 2016 and 2023. Among them, 184 patients underwent targeted sequencing. The median follow-up was 30.4 months (IQR 21.4-41.9, range 6.4-95.8). A clinico-genetic model m3-PRIMA-PI was developed using the multivariate Cox proportional hazards method, incorporating two clinical parameters (bone marrow involvement and elevated β2-MG) and three gene mutations (, , and ). Patients were categorized into low (69.0%), intermediate (21.7%), and high (9.2%) risk groups. Probabilities of treatment initiation at one year were 11.0% (95% CI, 5.2%-16.5%), 26.0% (95% CI, 10.7%-38.7%), and 54.3% (95% CI, 22.3%-73.1%); and at 2 years were 29.4% (95% CI, 20.2%-37.5%), 49.8% (95% CI, 31.1%-63.4%), and 93.5% (95% CI, 56.7%-99.0%), respectively. The predictive performance for TLT was superior with m3-PRIMA-PI, achieving a C-index of 0.66 (95% CI, 0.63-0.69), compared to established indexes like FLIPI (C-index 0.59, 95% CI, 0.56-0.62) and FLIPI2 (C-index 0.59, 95% CI, 0.55-0.61). The above results were further validated in an independent external cohort. The m3-PRIMA-PI may provide a promising tool for risk stratification in W&W FL patients.
诊断时肿瘤负荷较低的滤泡性淋巴瘤（FL）患者通常采用观察等待（W&W）策略。本研究旨在通过综合分析临床因素和基因突变，促进对W&W患者淋巴瘤治疗时间（TLT）预测的风险评估。对2016年至2023年间采用W&W策略治疗的214例FL患者进行了回顾性研究。其中，184例患者接受了靶向测序。中位随访时间为30.4个月（四分位间距21.4 - 41.9，范围6.4 - 95.8）。使用多变量Cox比例风险法建立了临床遗传模型m3-PRIMA-PI，纳入了两个临床参数（骨髓受累和β2-MG升高）和三个基因突变（，，和）。患者被分为低风险组（69.0%）、中风险组（21.7%）和高风险组（9.2%）。一年时开始治疗的概率分别为11.0%（95%置信区间，5.2% - 16.5%）、26.0%（95%置信区间，10.7% - 38.7%）和54.3%（95%置信区间，22.3% - 73.1%）；两年时分别为29.4%（95%置信区间，20.2% - 37.5%）、49.8%（95%置信区间，31.1% - 63.4%）和93.5%（95%置信区间，56.7% - 99.0%）。与FLIPI（C指数0.59，95%置信区间，0.56 - 0.62）和FLIPI2（C指数0.59，95%置信区间，0.55 - 0.61）等既定指标相比，m3-PRIMA-PI对TLT的预测性能更优，C指数达到0.66（95%置信区间，0.63 - 0.69）。上述结果在一个独立的外部队列中得到了进一步验证。m3-PRIMA-PI可能为W&W FL患者的风险分层提供一个有前景的工具。
