Data_Sheet_1_Ki67 Immunohistochemical Expression Level ≥70%, Bulky Presentation ≥7.5 cm, Meningeal Lymphomatosis, and Interim PET ΔSUVmax After 4 Treatment Cycles <71% as Parts of a Practical Scoring System to Predict Progression-Free Survival and Overall Survival in Diffuse Large B-Cell Lymphoma.PDF

Currently, prognostic models in diffuse large B-cell lymphoma (DLBCL) fail to closely reflect patients' biological, clinical, and survival heterogeneity. We, therefore, assessed the impact of clinical, biological, immunohistochemical (IHC), baseline (0), and interim (after 2 and 4 treatment cycles) PET (PET0, PET2, and PET4) data not yet included in any scoring system on DLBCL outcome. The analysis was conducted on 89 previously untreated adult patients of the Finistere Observatory Cohort (O.Ly.Fin) with documented DLBCL, recruited between January 2010 and December 2017, with progression-free survival (PFS) and overall survival (OS) as primary and secondary endpoints, respectively. Seventy-eight patients were treated with rituximab, cyclophosphamide, hydroxyadriamycin, vincristine, and prednisone (R-CHOP), while 11 received R-dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and hydroxyadriamycin (EPOCH). Patients were followed up until June 20, 2020. On multivariate analysis, Ki67 ≥ 70% on IHC (K), bulky presentation ≥7.5 cm (B), meningeal lymphomatosis (M), and PET0–PET4 ΔSUVmax <71% (P4) were identified as strong independent predictors of PFS, and all variables but bulky disease also strongly and independently predicted OS. Using these 4 parameters, we designed a scoring model named KBMP4 stratifying patients into low- (0 parameter), intermediate- (1 or 2), and high-risk (≥3) subgroups by the Kaplan–Meier analysis. At a median follow-up of 43 months, PFS and OS were both 100% in the low-risk subgroup, 71.4 and 90.5%, respectively, in the intermediate-risk subgroup, and 0 and 55.5%, respectively, in the high-risk subgroup. Use of the KBMP4 model in clinical practice may improve accuracy in prognostic prediction and treatment decisions in de novo DLBCL patients.

当前，弥漫大B细胞淋巴瘤（diffuse large B-cell lymphoma, DLBCL）的现有预后模型难以精准反映患者的生物学、临床及生存异质性。为此，本研究评估了尚未纳入任何评分系统的临床、生物学、免疫组化（immunohistochemical, IHC）、基线（治疗前0周期）以及中期（完成2和4个治疗周期后）PET显像（分别记为PET0、PET2及PET4）数据对DLBCL预后的影响。

本分析纳入2010年1月至2017年12月间招募的、经确诊的89例初治成人DLBCL患者，来自菲尼斯泰尔观测队列（Finistere Observatory Cohort, O.Ly.Fin），以无进展生存期（progression-free survival, PFS）和总生存期（overall survival, OS）分别作为主要和次要研究终点。其中78例患者接受利妥昔单抗、环磷酰胺、多柔比星、长春新碱及泼尼松（R-CHOP）方案治疗，11例接受剂量调整的依托泊苷、泼尼松、长春新碱、环磷酰胺及多柔比星（R-EPOCH）方案治疗。所有患者随访至2020年6月20日。

多因素分析显示，免疫组化Ki67≥70%（K）、大肿块病变（最大径≥7.5cm，B）、脑膜淋巴瘤浸润（M）以及PET0至PET4的最大标准化摄取值变化量（ΔSUVmax）<71%（P4）是PFS的强独立预测因子；除大肿块病变外，其余变量同样对OS具有显著独立预测价值。

基于上述4项参数，我们构建了名为KBMP4的评分模型，通过Kaplan-Meier分析将患者分为低危（0项参数阳性）、中危（1或2项参数阳性）及高危（≥3项参数阳性）三个亚组。中位随访时长为43个月时，低危亚组的PFS和OS均为100%；中危亚组分别为71.4%和90.5%；高危亚组分别为0%和55.5%。

在临床实践中应用KBMP4模型，可提升初治DLBCL患者的预后预测准确性，并辅助治疗决策制定。