我们进行了一项队列研究，纳入了在意大利国家卫生服务中心接受依鲁替尼治疗的所有复发/难治性慢性淋巴细胞白血病 (R/R CLL) 患者。该研究的中位随访时间为 42.2 个月（IQR 30.8-54.6 个月），涉及 3306 名患者，中位年龄为 72.1 岁，其中 42.6% 曾接受过 ≥2 种既往治疗。接受治疗并存活的估计 24 个月概率分别为 57.9%（95% 置信区间 [CI]：59.6-56.2）和 76.6%（95% CI：75.2-78.1）。中止治疗时间 (TTD) 为 31.3 个月 (95% CI: 29.5-33.5)。在 3306 名患者中，2015 年（60.9%）停止了治疗，其中 993 例归因于死亡或疾病进展（占所有病例的 30.0%）。在因疾病进展或死亡以外的原因停止治疗的 1022 名患者中，564 名患者 (17.1%) 是由于毒性或医疗决定而停止治疗，而 458 名患者 (13.8%) 失访。多变量分析显示，年龄、东部肿瘤合作组表现状态、既往治疗次数、最后一次治疗的难治性以及肾功能下降与较短的 TTD 和总生存期 (OS) 相关。 17p-和TP53突变的共存对TTD和OS具有独立的不利影响。非标准剂量与较短的 TTD 和晚期 OS 相关。进展后和因其他原因停药后的中位 OS 估计分别为 12.9 个月（95% CI：11.3-16.2）和 22.7 个月（95% CI：20.2-28.3）。这项大型现实世界研究表明，依鲁替尼是治疗 R/R CLL 的有效方法。基线患者特征和双重打击 TP53 畸变与较差的预后相关，并且由于 CLL 进展而停药预示着不良的结果。© 2024 作者。约翰·威利 (John Wiley) 出版的 HemaSphere

We performed a cohort study that included all patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) who received ibrutinib in the Italian National Health Service. With a median follow-up of 42.2 months (IQR 30.8-54.6 months), the study involved 3306 patients with a median age of 72.1 years, of whom 42.6% had received ≥2 previous lines of treatment. The estimated 24-month probabilities of being on treatment and alive were 57.9% (95% confidence interval [CI]: 59.6-56.2) and 76.6% (95% CI: 75.2-78.1), respectively. The median time to treatment discontinuation (TTD) was 31.3 months (95% CI: 29.5-33.5). Out of 3306 patients, 2015 (60.9%) discontinued treatment, with 993 cases attributed to death or disease progression (30.0% of all cases). Among the 1022 patients who discontinued treatment for reasons other than progression or death, 564 (17.1%) patients did so due to toxicity or medical decision, while 458 patients (13.8%) were lost to follow-up. Multivariable analysis revealed that age, Eastern Cooperative Oncology Group Performance Status, the number of previous lines of therapy, refractoriness to the last treatment, and reduced renal function were associated with shorter TTD and overall survival (OS). The coexistence of 17p- and TP53 mutations had an independent unfavorable impact on TTD and OS. Nonstandard doses were associated with shorter TTD and advanced stage with shorter OS. The median OS postprogression and postdiscontinuation for other reasons were estimated at 12.9 (95% CI: 11.3-16.2) and 22.7 months (95% CI: 20.2-28.3), respectively. This large real-world study shows that ibrutinib is an effective treatment for R/R CLL. Baseline patient characteristics and double-hit TP53 aberrations were associated with inferior prognosis, and discontinuation due to CLL progression portended a poor outcome.© 2024 The Author(s). HemaSphere published by John Wiley & Sons Ltd on behalf of European Hematology Association.