Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Division of Biomedical Statistics & Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
Oncologist. 2020 Nov;25(11):974-980. doi: 10.1634/theoncologist.2020-0388. Epub 2020 Sep 20.
Approximately 25% of patients with chronic lymphocytic leukemia (CLL) experience a flare of disease following ibrutinib discontinuation. A critical question is whether this phenomenon may also occur when ibrutinib is temporarily held. This study aimed to determine the frequency and characteristics of disease flares in this setting and assess risk factors and clinical outcomes.
We identified all patients with CLL seen at Mayo Clinic between October 2012 and March 2019 who received ibrutinib. Temporary interruptions in treatment and associated clinical findings were ascertained.
Among the 372 patients identified, 143 (38%) had at least one temporary interruption (median 1 hold, range 1-7 holds) in treatment. The median duration of interruption was 8 days (range 1-59 days) and the most common indication was periprocedural. Among the 143 patients with ≥1 hold, an associated disease flare was seen in 35 (25%) patients: mild (constitutional symptoms only) in 21 patients and severe (constitutional symptoms with exam/radiographic findings or laboratory changes) in 14 patients. Disease flare resolved with resuming ibrutinib in all patients. Predictive factors of disease flare included progressive disease at time of hold and ≥ 24 months of ibrutinib exposure. The occurrence of disease flare with an ibrutinib hold was associated with shorter event-free survival (hazard ratio 2.3; 95% confidence interval 1.3-4.1; p = .007) but not overall survival.
Temporary interruptions in ibrutinib treatment of patients with CLL are common, and one quarter of patients who held ibrutinib in this study experienced a disease flare. Resolution with resuming ibrutinib underscores the importance of awareness of this phenomenon for optimal management.
Ibrutinib is a very effective treatment for chronic lymphocytic leukemia (CLL) but needs to be taken continuously. Side effects, such as increased bleeding risk with procedures, require temporary interruptions in this continuous treatment. Rapid CLL progression following ibrutinib discontinuation has been increasingly recognized. This study demonstrates that similar flares in disease signs or symptoms may occur during ibrutinib holds as well. Importantly, management with restarting ibrutinib led to quick clinical improvement. Awareness of this phenomenon among clinicians is critical to avoid associated patient morbidity and premature cessation of effective treatment with ibrutinib if the flare is misidentified as true progression of disease.
约 25%的慢性淋巴细胞白血病（CLL）患者在停用伊布替尼后会出现疾病 flares。一个关键问题是，当伊布替尼被暂时停用，是否也会出现这种现象。本研究旨在确定在此情况下疾病 flares 的发生频率和特征，并评估风险因素和临床结局。
我们在梅奥诊所确定了 2012 年 10 月至 2019 年 3 月期间接受伊布替尼治疗的所有 CLL 患者。确定了治疗期间暂时中断和相关临床发现。
在确定的 372 名患者中，143 名（38%）至少有一次治疗中断（中位数 1 次停药，范围 1-7 次停药）。中断的中位时间为 8 天（范围 1-59 天），最常见的停药指征为围手术期。在 143 名有≥1 次停药的患者中，有 35 名（25%）患者出现疾病 flares：21 名患者为轻度（仅有全身症状），14 名患者为重度（全身症状伴有体格检查/影像学发现或实验室改变）。所有患者在重新开始伊布替尼治疗后，疾病 flares 均得到缓解。疾病 flares 的预测因素包括停药时疾病进展和伊布替尼暴露时间≥24 个月。伊布替尼停药时发生疾病 flares 与无事件生存时间缩短相关（风险比 2.3；95%置信区间 1.3-4.1；p=0.007），但与总生存时间无关。
伊布替尼治疗 CLL 患者的治疗中断很常见，本研究中接受伊布替尼治疗的患者中有四分之一出现疾病 flares。重新开始伊布替尼治疗可缓解疾病 flares，这凸显了了解这种现象对最佳管理的重要性。
伊布替尼是慢性淋巴细胞白血病（CLL）的一种非常有效的治疗方法，但需要连续服用。由于增加了手术出血风险等副作用，这种连续治疗需要暂时中断。伊布替尼停药后 CLL 迅速进展的情况已逐渐得到认识。本研究表明，在伊布替尼停药期间也可能出现类似的疾病迹象或症状 flares。重要的是，重新开始伊布替尼治疗可迅速改善临床情况。如果这种 flares 被错误地识别为疾病的真正进展，那么临床医生对此现象的认识至关重要，这可以避免与疾病相关的发病率，并避免过早停止有效的伊布替尼治疗。
