Outcomes and prognostic factors in 3306 patients with relapsed/refractory chronic lymphocytic leukemia treated with ibrutinib outside of clinical trials: A nationwide study

IF 7.6 2区 医学 Q1 HEMATOLOGY HemaSphere Pub Date : 2024-10-08 DOI:10.1002/hem3.70017
Gian Matteo Rigolin, Pier Paolo Olimpieri, Valentina Summa, Simone Celant, Lydia Scarfò, Maria Pia Ballardini, Antonio Urso, Silvia Gambara, Francesco Cavazzini, Paolo Ghia, Antonio Cuneo, Pierluigi Russo
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Abstract

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.

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在临床试验之外接受伊布替尼治疗的 3306 例复发/难治性慢性淋巴细胞白血病患者的疗效和预后因素:一项全国性研究。
我们开展了一项队列研究,纳入了意大利国家医疗服务机构所有接受伊布替尼治疗的复发/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),共涉及 3306 名患者,中位年龄为 72.1 岁,其中 42.6% 的患者曾接受过≥2 次治疗。估计24个月内接受治疗和存活的概率分别为57.9%(95%置信区间[CI]:59.6-56.2)和76.6%(95%置信区间:75.2-78.1)。停止治疗的中位时间(TTD)为 31.3 个月(95% 置信区间:29.5-33.5)。在 3306 例患者中,2015 例(60.9%)中止了治疗,其中 993 例是由于死亡或疾病进展(占所有病例的 30.0%)。在因病情进展或死亡以外的原因而中断治疗的 1022 例患者中,有 564 例(17.1%)患者是由于毒性或医疗决定而中断治疗,另有 458 例(13.8%)患者失去了随访机会。多变量分析显示,年龄、东部合作肿瘤学组(Eastern Cooperative Oncology Group)表现状态、既往治疗次数、对上次治疗的耐受性以及肾功能减退与较短的TTD和总生存期(OS)有关。17p基因突变和TP53基因突变同时存在对TTD和OS有不利影响。非标准剂量与较短的TTD有关,晚期与较短的OS有关。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)。这项大型真实世界研究表明,伊布替尼是治疗R/R CLL的有效方法。基线患者特征和双击TP53畸变与不良预后有关,因CLL进展而停药预示着不良预后。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
HemaSphere
HemaSphere Medicine-Hematology
CiteScore
6.10
自引率
4.50%
发文量
2776
审稿时长
7 weeks
期刊介绍: HemaSphere, as a publication, is dedicated to disseminating the outcomes of profoundly pertinent basic, translational, and clinical research endeavors within the field of hematology. The journal actively seeks robust studies that unveil novel discoveries with significant ramifications for hematology. In addition to original research, HemaSphere features review articles and guideline articles that furnish lucid synopses and discussions of emerging developments, along with recommendations for patient care. Positioned as the foremost resource in hematology, HemaSphere augments its offerings with specialized sections like HemaTopics and HemaPolicy. These segments engender insightful dialogues covering a spectrum of hematology-related topics, including digestible summaries of pivotal articles, updates on new therapies, deliberations on European policy matters, and other noteworthy news items within the field. Steering the course of HemaSphere are Editor in Chief Jan Cools and Deputy Editor in Chief Claire Harrison, alongside the guidance of an esteemed Editorial Board comprising international luminaries in both research and clinical realms, each representing diverse areas of hematologic expertise.
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