Timing matters: Impact of covalent BTK inhibitor dose modifications on outcomes in chronic lymphocytic leukemia/small lymphocytic leukemia—A 7-year real-world study

IF 5.6 2区医学 Q1 ONCOLOGY

Cancer Pub Date : 2026-09-15 DOI:10.1002/cncr.70578

Jiaojiao Zhang MS, Jing Luo MD, Xiaozhong Shen BS, Jiayi Ren MD, Weiyang Liu MD, Li Chen MD, Lu Jiang MD, Xiangqin Weng MD, Jin Wang MD, Jian-Qing Mi MD

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引用次数: 0

Abstract

Background

Covalent BTK inhibitors (cBTKis) are the cornerstone of chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) therapy, yet real-world data on dose modifications and their differential impact on long-term outcomes remain incompletely defined. This study investigated the incidence, timing, and the effectiveness of drug switching in a real-world CLL cohort.

Methods

In this 7-year retrospective real-world study, 324 CLL/SLL patients treated at a specialized Shanghai outpatient clinic (April 2018–April 2025; median follow-up, 42 months) were analyzed. Dose modifications were classified as dose interruption (DI) or dose reduction (DR). Their prognostic impact on progression-free (PFS) and overall survival (OS) was assessed by Kaplan–Meier analysis and multivariate Cox regression.

Results

The 42-month PFS rate was 70.2%. Of 324 patients, 229 (70.7%) experienced dose reductions or interruptions; infections were the predominant cause (61.9%). The full-dose (FD) group (n = 90) demonstrated superior 4-year PFS (93% vs. 58%, p < .001) and OS (98% vs. 76%, p = .007). Early modifications (0–3 months) were independent predictors of inferior PFS (hazard ratio [HR], 3.93, p = .008) and OS (HR, 3.29, p = .014). Prolonged DI (>14 days) was associated with inferior PFS (HR, 2.64) and OS (HR, 2.15), whereas DR and short DI (≤14 days) had negligible impact. Early (0–3 months) prolonged DI was devastating (3-year PFS, 41.2%; HR, 3.84, p < .001). cBTKi switching (n = 82; 100% nonprogression-driven) shortened DI (median, 6 vs. 14 days) and was independently associated with superior OS (HR, 0.34, p = .018) and PFS (HR, 0.36, p = .022).

Conclusions

Early prolonged DI is the dominant adverse prognostic factor in cBTKi-treated CLL/SLL. Proactive switching minimizes treatment gaps and improves survival, supporting a timing-aware, DI- versus DR-informed approach to dose management.

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时间问题：共价BTK抑制剂剂量改变对慢性淋巴细胞白血病/小淋巴细胞白血病结局的影响-一项为期7年的现实世界研究

背景：共价BTK抑制剂（cBTKis）是慢性淋巴细胞白血病(CLL)/小淋巴细胞白血病（SLL）治疗的基石，但剂量调整的实际数据及其对长期结局的差异影响仍未完全确定。本研究调查了现实世界CLL队列中药物转换的发生率、时间和有效性。方法：在这项为期7年的现实世界回顾性研究中，分析了324例在上海某专业门诊（2018年4月- 2025年4月，中位随访42个月）接受治疗的CLL/SLL患者。剂量改变分为剂量中断（DI）和剂量减少（DR）。通过Kaplan-Meier分析和多变量Cox回归评估其对无进展（PFS）和总生存期（OS）的预后影响。结果：42个月PFS为70.2%。在324例患者中，229例（70.7%）经历了剂量减少或中断；感染是主要原因（61.9%）。全剂量（FD）组（n = 90）显示优越的4年PFS（93%对58%，p 14天）与较差的PFS （HR, 2.64）和OS （HR, 2.15）相关，而DR和短DI（≤14天）的影响可以忽略不计。早期（0-3个月）延长的DI是毁灭性的（3年PFS， 41.2%； HR, 3.84, p）结论：早期延长的DI是cbtki治疗CLL/SLL的主要不良预后因素。主动转换可最大限度地减少治疗缺口，提高生存率，支持有时间意识的剂量管理方法。

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

Cancer 医学-肿瘤学

CiteScore

13.10

自引率

3.20%

发文量

480

审稿时长

2-3 weeks

期刊介绍： The CANCER site is a full-text, electronic implementation of CANCER, an Interdisciplinary International Journal of the American Cancer Society, and CANCER CYTOPATHOLOGY, a Journal of the American Cancer Society. CANCER publishes interdisciplinary oncologic information according to, but not limited to, the following disease sites and disciplines: blood/bone marrow; breast disease; endocrine disorders; epidemiology; gastrointestinal tract; genitourinary disease; gynecologic oncology; head and neck disease; hepatobiliary tract; integrated medicine; lung disease; medical oncology; neuro-oncology; pathology radiation oncology; translational research