Background/Objectives:Ibrutinib has revolutionized the treatment of chronic lymphocytic leukemia but has off-target side effects, most notably cardiac. In order to evaluate the efficacy and toxicity of ibrutinib treatment, risk factors for adverse outcomes and the influence of pretreatment cardiologic evaluation, KroHem collected data on Croatian patients with chronic lymphocytic leukemia treated with this drug.Methods:This is a retrospective survey performed in order to analyze the efficacy and toxicity of ibrutinib in a real-life setting. Patients starting therapy with ibrutinib for chronic lymphocytic leukemia between the time the drug became reimbursable in 2015 and 31 December 2021 were included, irrespective of treatment line.Results: We identified 436 patients fulfilling entry criteria; 404 (92.7%) responded to treatment. Cardiovascular side effects occurred in 25.0% of patients and hemorrhagic in 15.6%. The dose of ibrutinib was permanently reduced in 22.2% of patients. Median follow-up of the cohort was 29 months (IQR 18–41 months), estimated median overall survival 75 months (IQR 36 months–not reached), progression-free survival 54 months (IQR 24–81 months) and time on ibrutinib treatment 44 months (IQR 14–78 months). Factors significantly related to overall survival in multivariate analysis were stage, treatment line and age. Factors significantly related to progression-free survival in multivariate analysis were treatment line, age and pretreatment history or ECG finding of cardiac arrhythmia. Factors significantly related to time on ibrutinib treatment in multivariate analysis were age, pretreatment history or ECG finding of cardiac arrhythmia, and permanent dose reduction for toxicity. Sex, FISH and the presence of arterial hypertension were not independently significantly related to any of these outcomes. Pretreatment cardiologic consultation did not improve time on ibrutinib therapy, progression-free survival, overall survival, risk of stopping treatment due to cardiovascular side effects or risk of cardiovascular or sudden death, neither in the whole cohort nor in the subgroup of patients with and without pretreatment cardiac arrhythmia.Conclusions: Our analysis confirms the efficacy and tolerability of ibrutinib for the treatment of chronic lymphocytic leukemia. Patients older than 75 do significantly less well. Routine pretreatment cardiologic consultation does not improve outcomes and should not be considered part of standard pretreatment assessment without additional proof of its usefulness. Future investigations should aim at identifying predictive factors, mechanisms, and preventive strategies for reducing cardiotoxicity in chronic lymphocytic leukemia patients taking Bruton tyrosine kinase inhibitors.
背景/目的：伊布替尼已彻底改变慢性淋巴细胞白血病的治疗，但存在脱靶副作用，尤以心脏毒性最为显著。为评估伊布替尼治疗的疗效与毒性、不良结局的风险因素及治疗前心脏评估的影响，克罗地亚血液学协作组（KroHem）收集了该国接受该药物治疗的慢性淋巴细胞白血病患者数据。 方法：本研究为回顾性调查，旨在分析真实世界环境中伊布替尼的疗效与毒性。纳入2015年该药物纳入医保报销至2021年12月31日期间开始接受伊布替尼治疗的慢性淋巴细胞白血病患者，不限治疗线数。 结果：共纳入436例符合入组标准的患者，其中404例（92.7%）对治疗产生应答。25.0%的患者出现心血管副作用，15.6%出现出血性副作用。22.2%的患者永久性降低了伊布替尼剂量。中位随访时间为29个月（四分位距18-41个月），估计中位总生存期为75个月（四分位距36个月-未达到），无进展生存期为54个月（四分位距24-81个月），伊布替尼治疗持续时间为44个月（四分位距14-78个月）。多变量分析显示与总生存期显著相关的因素为疾病分期、治疗线数和年龄；与无进展生存期显著相关的因素为治疗线数、年龄及治疗前心律失常病史或心电图表现；与伊布替尼治疗持续时间显著相关的因素为年龄、治疗前心律失常病史或心电图表现，以及因毒性导致的永久性剂量降低。性别、荧光原位杂交结果及动脉高血压的存在与上述结局均无独立显著相关性。无论在整个队列中，还是在有无治疗前心律失常的亚组中，治疗前心脏专科会诊均未改善伊布替尼治疗持续时间、无进展生存期、总生存期、因心血管副作用停药风险或心血管性/猝死风险。 结论：本分析证实了伊布替尼治疗慢性淋巴细胞白血病的有效性与耐受性。75岁以上患者疗效显著较差。常规治疗前心脏专科会诊未能改善临床结局，在缺乏额外有效性证据的情况下不应视为标准治疗前评估的组成部分。未来研究应致力于识别接受布鲁顿酪氨酸激酶抑制剂治疗的慢性淋巴细胞白血病患者心脏毒性的预测因素、作用机制及预防策略。
肿瘤(癌症)患者之家