Clinical and Administrative Pharmacy, College of Pharmacy, University of Georgia, Athens, Georgia, USA.
School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
Cancer Med. 2024 Sep;13(18):e70258. doi: 10.1002/cam4.70258.
Bruton's tyrosine kinase inhibitors (BTKi) and the B-cell lymphoma 2 (BCL2) inhibitor venetoclax have significantly improved outcomes and achieved durable remission in patients with chronic lymphocytic leukemia (CLL). BTKi/venetoclax-treated patients with exposure to both novel agents (regardless of the reason for discontinuation) are classified as "double-exposed," and often have poor prognoses. This study aims to assess the efficacy and effectiveness of treatments in double-exposed CLL patients.
PubMed, Embase, and Web of Science databases were searched until December 2023.
We retrieved 3948 articles for screening and included 13 publications covering nine distinct studies. Three clinical trials reported a median PFS of 16.8 months with pirtobrutinib, 13 months with lisocabtagene maraleucel, and 10.1 months with nemtabrutnib. ORR ranged from 58% with nemtabrutinib and 80% with lisocabtagene maraleucel. In observational studies, PFS ranged from 3 months with chemoimmunotherapy to 12 months with BTKi, and ORR ranged from 31.8% with chemoimmunotherapy to 85.7% with chimeric antigen receptors (CAR) T-cell therapy.
This study highlights the limited clinical data on efficacy outcomes for double-exposed CLL/SLL patients. Pirtobrutinib, lisocabtagene maraleucel, and a combination of ibrutinib and venetoclax have shown promising effects. However, the scarcity of treatment options and efficacy data for patients who have failed BTKi and venetoclax underscores a significant unmet medical need.
布鲁顿酪氨酸激酶抑制剂（BTKi）和 B 细胞淋巴瘤 2（BCL2）抑制剂维奈托克显著改善了慢性淋巴细胞白血病（CLL）患者的预后，并实现了持久缓解。接受 BTKi/维奈托克治疗且同时暴露于两种新型药物（无论停药原因如何）的患者被归类为“双重暴露”，且通常预后较差。本研究旨在评估双重暴露 CLL 患者的治疗效果和有效性。
检索 PubMed、Embase 和 Web of Science 数据库，检索时间截至 2023 年 12 月。
我们筛选了 3948 篇文章，纳入了 13 篇涵盖 9 项不同研究的出版物。3 项临床试验报告了 pirtobrutinib 的中位 PFS 为 16.8 个月，lisocabtagene maraleucel 为 13 个月，nemtabrutnib 为 10.1 个月。ORR 范围为 nemtabrutinib 的 58%和 lisocabtagene maraleucel 的 80%。在观察性研究中，PFS 范围从化疗免疫治疗的 3 个月到 BTKi 的 12 个月，ORR 范围从化疗免疫治疗的 31.8%到嵌合抗原受体（CAR）T 细胞治疗的 85.7%。
本研究强调了双重暴露 CLL/SLL 患者疗效数据的有限性。Pirtobrutinib、lisocabtagene maraleucel 以及伊布替尼和维奈托克联合治疗显示出了有前景的效果。然而，对于已经失败 BTKi 和维奈托克的患者，治疗选择和疗效数据的缺乏突显了重大的未满足的医疗需求。
