Timing matters: Impact of covalent BTK inhibitor dose modifications on outcomes in chronic lymphocytic leukemia/small lymphocytic leukemia-A 7-year real-world study
In brief
Early prolonged BTK inhibitor interruptions drop 4-year survival to 41%
In a 7-year real-world cohort of 324 CLL/SLL patients, those who kept full-dose therapy had 98% overall survival at four years, whereas patients with early (first three months) interruptions longer than 14 days fell to 41% survival. Short interruptions or dose reductions did not affect outcomes, and switching drugs to shorten gaps improved survival.
- Journal
- Cancer (Q1)
- Published
- 15 September 2026
- Study design
- Retrospective cohort
- Evidence level
- Level 3, Low (CEBM 3b)
- Authors
- Jiaojiao Zhang, Jing Luo, Xiaozhong Shen, Jiayi Ren, Weiyang Liu, Li Chen, et al.
- PMID
- 42740716
- DOI
- 10.1002/cncr.70578
Why clinicians should know about it
- Picked for Hematology (paper of the day, 19 September 2026): Real‑world BTK inhibitor dose modifications in CLL
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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.