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期刊来源：JAMA

文献发表时间：2023-03-21

原文链接：https://jamanetwork.com/journals/jama/article-abstract/2802611

摘要内容如下：

重要性

慢性淋巴细胞白血病（CLL），定义为至少5 × 10^9/L血液中的单克隆B细胞，在美国每年影响超过200000人，并且与大约4410例死亡相关。慢性淋巴细胞性白血病（CLL）与免疫功能低下状态和感染并发症发生率增加有关。

观察

在诊断时，CLL患者的中位年龄为70岁，估计95%的患者至少有一种医学合并症。大约70%-80%的CLL患者在诊断时无症状，三分之一的CLL患者不需要治疗。已经开发了预后模型来估计首次治疗的时间和总生存率，但对于无症状的患者，无论疾病风险类别如何，临床观察是治疗的标准。有巨大或进行性淋巴结病或肝脾肿大的症状性疾病患者，以及中性粒细胞计数低、贫血或血小板减少和/或发热、盗汗和体重减轻症状（B症状）的患者，应给予治疗。对于这些患者，一线治疗包括含有共价Bruton酪氨酸激酶（BTK）抑制剂（acalabrutinib、zanubrutinib或ibrutinib）或B细胞白血病/淋巴瘤2（BCL2）抑制剂（Venetoclax）的方案。没有证据表明在另一门课之前开始任何一门课会改善结果。共价BTK抑制剂通常无限期使用。阿卡拉鲁替尼4年生存率约为88%，扎努布替尼2年生存率约为94%，伊布替尼7年生存率为78%。Venetoclax与obinutuzumab（一种单克隆抗CD20抗体）联合用于一线治疗1年（5年随访时总生存率为82%）。在共价BTK抑制剂和Venetoclax失败后，非共价BTK抑制剂Pitobrutinib的总体缓解率超过70%。磷脂酰肌醇3-激酶（PI3K）抑制剂（Idelalisib和Duvelisib）可用于治疗使用BTK抑制剂和Venetoclax进展的疾病，但患者需要密切监测不良事件，如自身免疫性疾病和感染。在多次复发的患者中，使用lisocabtagene maraleucel的嵌合抗原受体T细胞（CAR-T）治疗与45%的完全缓解率相关。CLL唯一可能的治疗方法是异基因造血细胞移植，在使用靶向药物后，这仍然是一种选择。

结论和相关性

在美国，超过20万人被诊断为慢性淋巴细胞性白血病（CLL），在美国，CLL每年导致大约4410人死亡。大约三分之二的患者最终需要治疗。高效的新型靶向药物包括BTK抑制剂，如阿卡拉鲁替尼、扎努布替尼、伊布替尼和吡托布替尼或BCL2抑制剂，如Venetoclax。

英文摘要原文如下：

Abstract

Importance  Chronic lymphocytic leukemia (CLL), defined by a minimum of 5 × 10^9/L monoclonal B cells in the blood, affects more than 200 000 people and is associated with approximately 4410 deaths in the US annually. CLL is associated with an immunocompromised state and an increased rate of complications from infections.

Observations  At the time of diagnosis, the median age of patients with CLL is 70 years, and an estimated 95% of patients have at least 1 medical comorbidity. Approximately 70% to 80% of patients with CLL are asymptomatic at the time of diagnosis, and one-third will never require treatment for CLL. Prognostic models have been developed to estimate the time to first treatment and the overall survival, but for patients who are asymptomatic, irrespective of disease risk category, clinical observation is the standard of care. Patients with symptomatic disease who have bulky or progressive lymphadenopathy or hepatosplenomegaly and those with a low neutrophil count, anemia, or thrombocytopenia and/or symptoms of fever, drenching night sweats, and weight loss (B symptoms) should be offered treatment. For these patients, first-line treatment consists of a regimen containing either a covalent Bruton tyrosine kinase (BTK) inhibitor (acalabrutinib, zanubrutinib, or ibrutinib) or a B-cell leukemia/lymphoma 2 (BCL2) inhibitor (venetoclax). There is no evidence that starting either class before the other improves outcomes. The covalent BTK inhibitors are typically used indefinitely. Survival rates are approximately 88% at 4 years for acalabrutinib, 94% at 2 years for zanubrutinib, and 78% at 7 years for ibrutinib. Venetoclax is prescribed in combination with obinutuzumab, a monoclonal anti-CD20 antibody, in first-line treatment for 1 year (overall survival, 82% at 5-year follow-up). A noncovalent BTK inhibitor, pitobrutinib, has shown an overall response rate of more than 70% after failure of covalent BTK inhibitors and venetoclax. Phosphoinositide 3′-kinase (PI3K) inhibitors (idelalisib and duvelisib) can be prescribed for disease that progresses with BTK inhibitors and venetoclax, but patients require close monitoring for adverse events such as autoimmune conditions and infections. In patients with multiple relapses, chimeric antigen receptor T-cell (CAR-T) therapy with lisocabtagene maraleucel was associated with a 45% complete response rate. The only potential cure for CLL is allogeneic hematopoietic cell transplant, which remains an option after use of targeted agents.

Conclusions and Relevance  More than 200 000 people in the US are living with a CLL diagnosis, and CLL causes approximately 4410 deaths each year in the US. Approximately two-thirds of patients eventually need treatment. Highly effective novel targeted agents include BTK inhibitors such as acalabrutinib, zanubrutinib, ibrutinib, and pirtobrutinib or BCL2 inhibitors such as venetoclax.

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