Department of Cardiology, Hospital Alemão Oswaldo Cruz, Rua Treze de Maio 1815, 1º subsolo Bloco B, Bela Vista, São Paulo, SP, 01323-020, Brazil.
Department of Hematology and Bone Marrow Transplant, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil.
Ann Hematol. 2024 Nov;103(11):4613-4620. doi: 10.1007/s00277-024-05921-7. Epub 2024 Aug 17.
Bruton tyrosine kinase (BTK) inhibitors play an important role in targeted treatment of B-cell lymphoproliferative disorders. However, adverse events may limit the proper course of treatment in many patients. The purpose of this study is to compare the risk of cardiovascular and non-cardiovascular adverse events in patients with chronic lymphocytic leukemia (CLL) or small cell lymphocytic lymphoma (SLL) treated with the first-generation BTK inhibitor ibrutinib versus second-generation acalabrutinib, using real-world data from a collaborative multinational network. We used data from the network (TriNetX), which encompasses more than 100 healthcare organizations worldwide. We queried the database for patients aged ≥ 18 years with chronic lymphocytic leukemia or small-cell lymphomas treated with ibrutinib or acalabrutinib in the past ten years before the analysis. We used propensity score matching to balance the cohorts. The 3-year cumulative incidences and hazard ratios for the following outcomes were calculated: atrial flutter or fibrillation, other arrhythmias, heart failure, ischemic stroke or peripheral embolism, acute coronary syndrome, bleeding, and sepsis. We compared 2,107 patients in each group. Atrial fibrillation or flutter occurred in 150 (7.1%) patients with acalabrutinib and 310 (14.7%) patients with ibrutinib during the 3-year follow-up (hazard ratio, 0.68, 95% CI 0.55-0.84). New-onset hypertension occurred in 342 (16.3%) patients in the acalabrutinib group and 584 (27.7%) patients in the ibrutinib group (hazard ratio 0.81, 95% CI 0.66-0.98). Sepsis was diagnosed in 136 (6.5%) patients in the acalabrutinib group versus 239 (11.3%) patients in the ibrutinib group (hazard ratio 0.77, 95 CI 0.60-0.98). The two groups had no significant differences concerning the other adverse events. In a large retrospective cohort using real-world data from electronic medical registers, patients with CLL or SLL treated with acalabrutinib had a better cardiovascular and non-cardiovascular safety profile than those treated with ibrutinib, with lower risks of atrial flutter or fibrillation, new-onset arterial hypertension, and sepsis.
布鲁顿酪氨酸激酶（BTK）抑制剂在 B 细胞淋巴增生性疾病的靶向治疗中发挥着重要作用。然而，不良反应可能会限制许多患者的治疗进程。本研究的目的是使用来自合作的跨国网络的真实世界数据，比较第一代 BTK 抑制剂伊布替尼与第二代阿卡替尼治疗慢性淋巴细胞白血病（CLL）或小细胞淋巴瘤（SLL）患者的心血管和非心血管不良事件的风险。我们使用来自网络（TriNetX）的数据，该网络涵盖了全球 100 多个医疗保健组织。在分析前的过去十年中，我们在数据库中查询了接受伊布替尼或阿卡替尼治疗的年龄≥18 岁的 CLL 或小细胞淋巴瘤患者的数据。我们使用倾向评分匹配来平衡队列。计算了以下结果的 3 年累积发生率和风险比：心房颤动或扑动、其他心律失常、心力衰竭、缺血性中风或外周栓塞、急性冠状动脉综合征、出血和败血症。我们比较了每组 2107 例患者。在 3 年的随访中，阿卡替尼组有 150 例（7.1%）患者发生心房颤动或扑动，伊布替尼组有 310 例（14.7%）患者发生心房颤动或扑动（风险比，0.68，95%CI 0.55-0.84）。阿卡替尼组有 342 例（16.3%）患者新发高血压，伊布替尼组有 584 例（27.7%）患者新发高血压（风险比，0.81，95%CI 0.66-0.98）。阿卡替尼组有 136 例（6.5%）患者诊断为败血症，伊布替尼组有 239 例（11.3%）患者诊断为败血症（风险比，0.77，95%CI 0.60-0.98）。两组在其他不良事件方面无显著差异。在一项使用电子病历真实世界数据的大型回顾性队列研究中，与接受伊布替尼治疗的患者相比，接受阿卡替尼治疗的 CLL 或 SLL 患者具有更好的心血管和非心血管安全性，心房颤动或扑动、新发动脉高血压和败血症的风险较低。
