Breinholt Marie Fredslund, Schejbel Lone, Gang Anne Ortved, Christensen Ib Jarle, Nielsen Torsten Holm, Pedersen Lars Møller, Høgdall Estrid, Nørgaard Peter
Department of Pathology, Herlev-Gentofte Hospital, Herlev, Denmark.
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Eur J Haematol. 2025 Mar;114(3):573-579. doi: 10.1111/ejh.14364. Epub 2024 Dec 18.
Large B-cell lymphoma (LBCL) taxonomy has moved in the direction of a molecular classification, but further clinical experience is needed. We present high-risk gene mutations, which predict outcome in an exploratory study of a consecutive real-world cohort of patients with primary LBCL treated with R-CHOP or R-CHOP-like therapy.
The study was a Registry Study Research Project. Sixty-one patients with LBCL, who had a diagnostic tumor sample successfully examined with a 59-gene next-generation sequencing (NGS) panel as a part of routine clinical work, were included in an otherwise unselected cohort. Data were extracted from patient files and pathology reports.
Mutations in NOTCH2 (HR 9.69; 95% CI [2.46-38.11]; p = 0.0012), PRDM1 (HR 3.54; 95% CI [1.03-12.22]; p = 0.045), and TP53 (HR 5.89; 95% CI [1.71-20.32]; p = 0.005) were significantly associated with inferior survival in patients with primary LBCL treated with intention to cure with at least three series of R-CHOP or R-CHOP-like therapy. Neither MYD88 (HR 0.66; 95% CI (0.17-2.49), p = 0.54) nor CD79B (HR 0.84;95% CI (0.18-3.88), p = 0.82) mutations were associated with inferior survival.
With a targeted gene panel and NGS methodology feasible in daily diagnostic routine, we identified high-risk gene mutations with a significant prognostic impact of which TP53 mutations were reproducible across validation cohorts.
大B细胞淋巴瘤（LBCL）的分类已朝着分子分类的方向发展，但仍需要更多的临床经验。我们在一项探索性研究中展示了高危基因突变，该研究针对接受R-CHOP或类似R-CHOP疗法治疗的原发性LBCL患者的连续真实世界队列进行，这些突变可预测预后。
该研究是一项注册研究项目。61例LBCL患者作为常规临床工作的一部分，其诊断性肿瘤样本成功通过59基因下一代测序（NGS）面板进行检测，被纳入一个未经过其他筛选的队列。数据从患者病历和病理报告中提取。
在接受至少三个疗程R-CHOP或类似R-CHOP疗法进行根治性治疗的原发性LBCL患者中，NOTCH2突变（风险比[HR] 9.69；95%置信区间[CI] [2.46 - 38.11]；p = 0.0012）、PRDM1突变（HR 3.54；95% CI [1.03 - 12.22]；p = 0.045）和TP53突变（HR 5.89；95% CI [1.71 - 20.32]；p = 0.005）与较差的生存率显著相关。MYD88突变（HR 0.66；95% CI（0.17 - 2.49），p = 0.54）和CD79B突变（HR 0.84；95% CI（0.18 - 3.88），p = 0.82）均与较差的生存率无关。
通过在日常诊断流程中可行的靶向基因面板和NGS方法，我们鉴定出具有显著预后影响的高危基因突变，其中TP53突变在验证队列中具有可重复性。
