Impact of ibrutinib dose adjustment on TTNT in first-line CLL/SLL: a real-world analysis using target trial emulation

Blood Neoplasia Pub Date : 2024-06-10 DOI:10.1016/j.bneo.2024.100022

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Abstract

Ibrutinib, a once-daily Bruton tyrosine kinase inhibitor, is a standard-of-care first-line (1L) treatment for patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Dosing flexibility (adjustment to daily dose of <420 mg/d) with ibrutinib can help prevent recurrence or worsening of adverse events while maintaining long-term efficacy. This study compared time to next treatment among patients with CLL/SLL in the United States initiating 1L single-agent ibrutinib at 420 mg/d (index date) and staying on this dose vs patients with dose adjustment (DA) within 3 to 12 months. Two databases were used: Komodo claims (a majority from community practices) and Acentrus electronic medical records (from academic and nonteaching hospital systems). To account for immortal time bias (patients with DA survived on 1L therapy until DA) and overlap between follow-up time and definition of treatment strategies, a target trial emulation approach was used, in which patients were cloned at index date and contributed follow-up to both treatment strategy arms until deviation from the strategy. Among 3343 patients in Komodo (mean age: 67.5 years; 37.6% female) and 1171 patients in Acentrus (mean age: 70.4 years; 34.6% female) who initiated 1L single-agent ibrutinib 420 mg/d, 18.0% and 19.6%, respectively, had a DA. DA was not associated with an increased risk of having a next treatment in both databases (adjusted hazard ratio [95% confidence interval]: Komodo: 0.95 [0.80-1.14], Acentrus: 1.14 [0.80-1.62]). These findings suggest that a flexible dosing approach with ibrutinib may be effective in allowing patients to achieve optimal outcomes while remaining on long-term continuous 1L treatment.

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伊布替尼剂量调整对一线CLL/SLL患者TTNT的影响：利用目标试验模拟进行的真实世界分析

摘要伊布替尼是一种每日一次的布鲁顿酪氨酸激酶抑制剂，是慢性淋巴细胞白血病（CLL）/小淋巴细胞淋巴瘤（SLL）患者的标准一线（1L）治疗药物。伊布替尼的剂量灵活性（调整为每日420毫克/天）有助于防止不良反应复发或恶化，同时保持长期疗效。这项研究比较了美国CLL/SLL患者以420毫克/天（指标日）的剂量开始1L单药伊布替尼治疗，并在3至12个月内保持这一剂量与进行剂量调整（DA）的患者进行下一次治疗的时间。我们使用了两个数据库：Komodo报销单（大部分来自社区诊所）和Acentrus电子病历（来自学术和非教学医院系统）。为了考虑不死时间偏差（DA 患者在接受 1L 治疗后存活至 DA）以及随访时间与治疗策略定义之间的重叠，采用了目标试验仿真法，即在指数日期克隆患者，并对两种治疗策略臂进行随访，直至偏离治疗策略。在Komodo的3343名患者（平均年龄：67.5岁；37.6%为女性）和Acentrus的1171名患者（平均年龄：70.4岁；34.6%为女性）中，开始使用1L单药伊布替尼420 mg/d的患者中，分别有18.0%和19.6%出现DA。在这两个数据库中，DA与下一次治疗风险的增加无关（调整后的危险比[95%置信区间]：0.5%）：科莫多0.95 [0.80-1.14]，Acentrus：1.14 [0.80-1.62]）。这些研究结果表明，伊布替尼的灵活给药方法可以有效地使患者在长期持续接受1L治疗的同时获得最佳疗效。

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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Blood Neoplasia

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