Background: Fixed-duration venetoclax plus rituximab (VR) is a standard therapy for relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). However, evidence supporting its use after covalent BTK inhibitor (c-BTKi) therapy is scarce in clinical trials and limited in real-world settings. Objectives: To assess the efficacy and safety of VR in a real-world cohort of patients with R/R CLL, including cBTKi-pretreated individuals, and to contextualize outcomes alongside published real-world studies and registrational trials of alternative therapies. Methods: We retrospectively analyzed 37 patients with R/R CLL treated with VR at our center between April 2018 and November 2024. Baseline characteristics, treatment responses, minimal residual disease (MRD), and adverse events were recorded. Survival was estimated using the Kaplan–Meier method. A structured review of relevant real-world evidence and pirtobrutinib clinical trials was also conducted. Results: Median age was 67 years; 35.1% had prior cBTKi exposure. The overall response rate (ORR) was 91.7% (22/24 evaluable patients), with 66.7% achieving complete remission (CR). Among evaluable c-BTKi-pretreated patients, the ORR was 87.5% (7/8) and the CR rate was 62.5%. Undetectable MRD (uMRD) rates were 78.6% in peripheral blood and 71.4% in bone marrow. Thirty-month progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS) were >90% for the whole cohort and for c-BTKi-pretreated patients. The most frequent adverse event was neutropenia grade ≥ 3, especially during combination therapy, which is easily managed with GCSF support. Conclusions: Our real-world evidence shows that VR is an effective and well-tolerated option even after c-BTKi therapy in R/R CLL. These data complement evidence from emerging therapies and inform post-c-BTKi treatment selection in clinical practice.
背景：固定疗程的维奈托克联合利妥昔单抗（VR）是复发/难治性（R/R）慢性淋巴细胞白血病（CLL）的标准疗法。然而，在临床试验中支持其用于共价BTK抑制剂（c-BTKi）治疗后患者的证据有限，在真实世界环境中的研究也较少。目的：评估VR在真实世界R/R CLL患者队列（包括cBTKi预处理患者）中的疗效和安全性，并将结果与已发表的其他疗法的真实世界研究和注册试验进行背景化比较。方法：我们回顾性分析了2018年4月至2024年11月期间在我中心接受VR治疗的37例R/R CLL患者。记录了基线特征、治疗反应、微小残留病（MRD）和不良事件。使用Kaplan-Meier法估计生存期。同时对相关的真实世界证据和吡托布鲁替尼临床试验进行了结构化综述。结果：中位年龄为67岁；35.1%的患者既往接受过cBTKi治疗。总体缓解率（ORR）为91.7%（24例可评估患者中的22例），其中66.7%达到完全缓解（CR）。在可评估的c-BTKi预处理患者中，ORR为87.5%（8例中的7例），CR率为62.5%。外周血和骨髓中检测不到MRD（uMRD）的比例分别为78.6%和71.4%。整个队列以及c-BTKi预处理患者的30个月无进展生存期（PFS）、至下次治疗时间（TTNT）和总生存期（OS）均>90%。最常见的不良事件是≥3级中性粒细胞减少症，尤其在联合治疗期间，通过GCSF支持易于管理。结论：我们的真实世界证据表明，即使在c-BTKi治疗后，VR对于R/R CLL患者仍是一种有效且耐受性良好的选择。这些数据补充了新兴疗法的证据，并为临床实践中c-BTKi治疗后的方案选择提供了参考。
肿瘤(癌症)患者之家