Next Generation BTK Inhibitors in CLL: Evolving Challenges and New Opportunities.
Next Generation BTK Inhibitors in CLL: Evolving Challenges and New Opportunities.
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DOI：
10.3390/cancers15051504
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发表时间：
2023-02-27
期刊：
影响因子：
5.2
通讯作者：
Tedeschi, Alessandra
中科院分区：
文献类型：
--
作者：
Frustaci, Anna Maria;Deodato, Marina;Zamprogna, Giulia;Cairoli, Roberto;Montillo, Marco;Tedeschi, Alessandra
慢性淋巴细胞白血病（CLL）的治疗方案正在迅速发展。经过更长时间的观察，尽管临床结果显着，但伊布替尼治疗仍与长期毒性和耐药性相关。基于BTK抑制的新策略正在开发中，为不耐受和难治性患者提供有效的挽救治疗。本文就新一代BTK抑制剂在慢性淋巴细胞白血病中的作用作一综述。伊布替尼彻底改变了CLL治疗方法和预后，即使在延长随访时也证明了其疗效和安全性。在过去的几年中，已经开发了几种下一代抑制剂，以克服持续治疗患者中毒性或耐药性的发生。在两项III期临床试验的头对头比较中，acalabrutinib和zanuinib的不良事件发生率均低于iinib。尽管如此，耐药突变仍然是连续治疗的一个问题，并且在第一代和下一代共价抑制剂中得到了证实。可逆性抑制剂的疗效与既往治疗和BTK突变的存在无关。目前正在开发CLL中的其他策略，特别是对于高风险患者，包括BTK抑制剂与BCl2抑制剂的组合，有或没有抗CD20单克隆抗体。最后，在使用共价和非共价BTK和BCl2抑制剂进展的患者中，正在研究BTK抑制的新机制。在这里，我们总结和讨论结果的主要经验，不可逆和可逆的BTK抑制剂在CLL。
Chronic lymphocytic leukemia (CLL) treatment scenario is rapidly evolving. As a consequence of longer observation, despite remarkable clinical results, treatment with ibrutinib is associated with long-term toxicities and resistance. New strategies based on BTK inhibition are under development, offering effective salvage treatment both to intolerant and refractory patients. This review is aimed at summarizing and discussing the role of next-generation BTK inhibitors in CLL. Ibrutinib revolutionized the CLL treatment approach and prognosis demonstrating its efficacy and safety even at extended follow-up. During the last few years, several next-generation inhibitors have been developed to overcome the occurrence of toxicity or resistance in patients on continuous treatment. In a head-to-head comparison of two phase III trials, both acalabrutinib and zanubrutinib demonstrated a lower incidence of adverse events in respect to ibrutinib. Nevertheless, resistance mutations remain a concern with continuous therapy and were demonstrated with both first- and next-generation covalent inhibitors. Reversible inhibitors showed efficacy independently of previous treatment and the presence of BTK mutations. Other strategies are currently under development in CLL, especially for high-risk patients, and include BTK inhibitor combinations with BCl2 inhibitors with or without anti-CD20 monoclonal antibodies. Finally, new mechanisms for BTK inhibition are under investigations in patients progressing with both covalent and non-covalent BTK and BCl2 inhibitors. Here we summarize and discuss results from main experiences on irreversible and reversable BTK inhibitors in CLL.
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影响因子：
51.1
作者：
Davids, Matthew S.;Lampson, Benjamin L.;Brown, Jennifer R.
通讯作者：
Brown, Jennifer R.
在先前治疗的慢性淋巴细胞性白血病中，阿卡劳替尼与伊布鲁替尼：第一次随机III期试验的结果。
DOI：
10.1200/jco.21.01210
发表时间：
2021-11-01
期刊：
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
影响因子：
--
作者：
Byrd JC;Hillmen P;Ghia P;Kater AP;Chanan-Khan A;Furman RR;O'Brien S;Yenerel MN;Illés A;Kay N;Garcia-Marco JA;Mato A;Pinilla-Ibarz J;Seymour JF;Lepretre S;Stilgenbauer S;Robak T;Rothbaum W;Izumi R;Hamdy A;Patel P;Higgins K;Sohoni S;Jurczak W
通讯作者：
Jurczak W
影响因子：
10.1
作者：
Allan JN;Pinilla-Ibarz J;Gladstone DE;Patel K;Sharman JP;Wierda WG;Choi MY;O'Brien SM;Shadman M;Davids MS;Pagel JM;Yimer HA;Ward R;Acton G;Taverna P;Combs DL;Fox JA;Furman RR;Brown JR
通讯作者：
Brown JR
影响因子：
4.5
作者：
Edlund, Helena;Lee, Sun Ku;Al-Huniti, Nidal
通讯作者：
Al-Huniti, Nidal
影响因子：
7.5
作者：
Blombery, Piers;Thompson, Ella R.;Lew, Thomas E.;Tiong, Ing Soo;Bennett, Rory;Cheah, Chan Y.;Lewis, Katharine Louise;Handunnetti, Sasanka M.;Tang, Chloe Pek Sang;Roberts, Andrew;Seymour, John F.;Tam, Constantine S.
通讯作者：
Tam, Constantine S.