Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Leuk Lymphoma. 2020 Oct;61(10):2375-2382. doi: 10.1080/10428194.2020.1772477. Epub 2020 Jun 6.
Immune dysregulation in chronic lymphocytic leukemia (CLL) contributes to a high rate of infections and morbidity. The Bruton tyrosine kinase (BTK) inhibitors ibrutinib and acalabrutinib mark major breakthroughs in the treatment of CLL, however many patients require long-term therapy with these agents. Despite receiving effective therapy for CLL, patients on BTK inhibitors remain immunocompromised and at risk of infectious complications. We previously reported that treatment of CLL with ibrutinib leads to partial reconstitution of humoral immunity and fewer infections during the first two years of therapy. It is currently unclear whether the positive effects of ibrutinib on the immune system are sustained during long-term therapy. Acalabrutinib is a newer, more selective BTK inhibitor than ibrutinib; however a detailed evaluation of the immunologic impact of acalabrutinib therapy is lacking. Herein, utilizing two independent trials, we assessed the immunological effects and infectious risk of ibrutinib and acalabrutinib treatment in patients with CLL.
慢性淋巴细胞白血病（CLL）中的免疫失调导致感染率和发病率高。布鲁顿酪氨酸激酶（BTK）抑制剂依鲁替尼和阿卡替尼在 CLL 的治疗方面取得了重大突破，然而许多患者需要长期接受这些药物的治疗。尽管 CLL 患者接受了有效的治疗，但 BTK 抑制剂的使用者仍然免疫功能低下，存在感染并发症的风险。我们之前的研究报告表明，用依鲁替尼治疗 CLL 会导致体液免疫的部分重建，并在治疗的前两年减少感染。目前尚不清楚依鲁替尼对免疫系统的积极影响是否在长期治疗中持续存在。阿卡替尼是一种比依鲁替尼更新、更具选择性的 BTK 抑制剂；然而，缺乏对阿卡替尼治疗免疫影响的详细评估。在此，我们利用两项独立的试验，评估了依鲁替尼和阿卡替尼治疗 CLL 患者的免疫效应和感染风险。
