摘要目的:探讨奥布替尼联合R-CHOP（OR-CHOP）方案治疗MCD亚型弥漫大B细胞淋巴瘤（DLBCL）患者的疗效及安全性。方法:对2022年6月至2023年6月共23例在南京医科大学第一附属医院血液科确诊为DLBCL且基线肿瘤组织和（或）基线血浆根据LymphGen算法为MCD亚型的患者进行回顾性分析，患者第1个疗程使用R-CHOP或R-miniCHOP方案，第2～6个疗程使用OR-CHOP或OR-miniCHOP方案（21 d为1个疗程），第7～8个疗程使用利妥昔单抗单药。结果:23例患者的中位年龄58（30～81）岁，11例（47.8%）年龄>60岁，15例（65.2%）国际预后指数（IPI）评分为3～5分。组织突变频率前10的基因分别为：PIM1（78.3%）、MYD88（69.6%）、ETV6（43.5%）、BTG1（39.1%）、CD79B（43.5%）、HIST1H1E（39.1%）、BTG2（34.8%）、KMT2D（30.4%）、CD58（26.1%）和CDKN2B（21.7%）。组织和血浆基因检测突变的一致率为80%，且基线血浆循环肿瘤DNA（ctDNA）负荷与LDH以及IPI评分密切相关（ P<0.05）。所有患者均接受5个疗程OR-CHOP方案治疗，中期（3个疗程后）评估总有效率（ORR）为100%（23/23），22例（95.65%）患者获得完全缓解（CR），1例（4.35%）患者获得部分缓解（PR）。治疗结束后ORR为95.65%（22/23），21例（91.30%）患者获得CR，1例（4.35%）患者获得PR，1例（4.35%）患者疾病进展（PD）。21例患者有治疗后血浆ctDNA（EOT-ctDNA）的动态随访结果，4例（19.0%）未达到EOT-ctDNA清零，17例（81.0%）得EOT-ctDNA清零。中位随访时间为20.8（15.3～30.0）个月，中位无进展生存（PFS）和总生存（OS）期均未达到。2年PFS率为71.8%（95% CI 54.7%～94.2%），2年OS率为91.3%（95% CI 80.5%～100.0%）。此外，OR-CHOP方案临床应用的总体耐受良好，主要不良反应是血液学毒性。 结论:OR-CHOP方案治疗MCD亚型DLBCL患者是安全且存在临床获益的。

abstractsObjective:To investigate the efficacy and safety of orelabrutinib combined with R-CHOP in the treatment of MCD subtype diffuse large B cell lymphoma (DLBCL) .Methods:Twenty-three MCD subtype patients whose gene-subtype classification was based on baseline tumor tissue and/or baseline plasma using the LymphGen algorithm from June 2022 to June 2023 in the First Affiliated Hospital of Nanjing Medical University were retrospectively enrolled in the analysis. All patients were treated with R-CHOP or R-miniCHOP in Course 1, OR-CHOP or OR-miniCHOP (21 days for one course) in Courses 2-6, and R-monotherapy in Courses 7-8.Results:Of the 23 patients, the median age was 58 years (range: 30-81 years), and 11 (47.8% ) aged >60 years. Fifteen cases (65.2% ) had international prognostic index (IPI) scores of 3 to 5. The top 10 mutated genes in the gDNA tissues were PIM1 (78.3% ), MYD88 (69.6% ), ETV6 (43.5% ), BTG1 (39.1% ), CD79B (43.5% ), HIST1H1E (39.1% ), BTG2 (34.8% ), KMT2D (30.4% ), CD58 (26.1% ), and CDKN2B (21.7% ). The consistency rate of the tissue and plasma mutations was 80%, while the baseline plasma ctDNA burden was closely correlated with the LDH levels and IPI scores ( P<0.05). All patients received 5 courses of OR-CHOP regimens. The mid-term (after 3 courses) evaluation showed that the overall response rate (ORR) was 100% (23/23), with 22 patients (95.65% ) achieving complete remission (CR), and 1 patient (4.35% ) achieving partial remission (PR). The ORR after the end of treatment (EOT) was 95.65% (22/23). Moreover, 21 patients (91.30% ) obtained CR, 1 patient (4.35% ) obtained PR, and 1 patient (4.35% ) obtained progression disease (PD). Of the 21 patients who had the dynamic EOT-ctDNA burden, only four patients (19.0% ) did not achieve EOT-ctDNA clearance, while the other 17 patients (81.0% ) achieved EOT-ctDNA clearance. The median follow-up time was 20.8 (15.3-30.0) months, while the median progression-free survival (PFS) and overall survival (OS) were not reached. The 2-year PFS rate was 71.8% (95% CI 54.7% -94.2% ), while the 2-year OS rate was 91.3% (95% CI 80.5% -100.0% ). Furthermore, the OR-CHOP regimen was generally well tolerated during clinical use, with hematological toxicity being the main adverse effect. Conclusion:This study revealed that the OR-CHOP regimen can be used as an effective and safe first-line treatment for MCD subtype DLBCL.