Review of Venetoclax in CLL, AML and Multiple Myeloma.
Review of Venetoclax in CLL, AML and Multiple Myeloma.
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DOI：
10.3390/jpm11060463
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发表时间：
2021-05-24
影响因子：
--
通讯作者：
Anderson MA
中科院分区：
文献类型：
--
作者：
Lasica M;Anderson MA
维奈托克是一种高度选择性和有效的B细胞淋巴瘤-2（BCL-2）抑制剂，能够恢复癌细胞的凋亡潜力。由于其全部功能尚未探索，它已经改变了血液恶性肿瘤的治疗前景，特别是慢性淋巴细胞白血病（CLL），急性髓性白血病（AML）和多发性骨髓瘤（MM）。在CLL中，它作为单药治疗和联合治疗都显示出显著的疗效。根据来自MURANO和CLL 14研究的数据，维奈托克与抗CD 20抗体的固定持续时间联合治疗目前是许多国家的标准治疗。在AML中，尽管作为单一药物的疗效有限，但维奈托克联合治疗已显示出令人鼓舞的结果，包括快速，持久的反应和可接受的毒性，特别是在老年，不适合的患者人群中。易位型多发性骨髓瘤（t）（11;14）具有高BCL-2/骨髓细胞白血病序列-1（MCL-1）和BCL-2/BCL-XL比率，因此特别适合基于维奈托克的治疗。尽管在这些疾病中具有广泛和不断发展的临床作用，但维奈托克治疗并不能治愈，随着时间的推移，克隆进化和疾病复发似乎是常态。虽然已经确定了各种不同的耐药机制，经常出现在亚克隆模式，全貌还有待表征。需要进一步阐明各种因素的复杂相互作用，为旨在规避耐药性和提高疾病控制持久性的合理联合疗法铺平道路。系列分子研究可以帮助鉴定新的遗传学上显著的和/或可靶向的突变。
Venetoclax is a highly selective and effective B-cell lymphoma-2 (BCL-2) inhibitor, which is able to reinstate the apoptotic potential of cancer cells. With its full repertoire yet to be explored, it has changed the therapeutic landscape in haematological malignancies, and most particularly chronic lymphocytic leukaemia (CLL), acute myeloid leukaemia (AML) and multiple myeloma (MM). In CLL, it has shown remarkable efficacy both as monotherapy and in combination therapy. Based on data from MURANO and CLL14 studies, fixed-duration combination therapy of venetoclax with anti-CD20 antibody is now the standard of care in numerous countries. In AML, although of limited efficacy as a single agent, venetoclax combination therapy has demonstrated encouraging outcomes including rapid, durable responses and acceptable toxicity, particularly in the older, unfit patient population. Multiple myeloma with translocation (t)(11;14) harbours high BCL-2/ myeloid cell leukaemia sequence-1 (MCL-1) and BCL-2/BCL-XL ratio and is, therefore, particularly suited for venetoclax-based therapy. Despite a wide ranging and evolving clinical role in these diseases, venetoclax treatment is not curative and, over time, clonal evolution and disease relapse appear to be the norm. While a variety of distinct resistance mechanisms have been identified, frequently emerging in a sub-clonal pattern, the full picture is yet to be characterised. Further illumination of the complex interplay of various factors is needed to pave the way for rational combination therapies aimed at circumventing resistance and improving durability of disease control. Serial molecular studies can aid in identification of new prognostically significant and/or targetable mutations.
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影响因子：
20.3
作者：
Anderson, Mary Ann;Deng, Jing;Roberts, Andrew W.
通讯作者：
Roberts, Andrew W.
DOI：
10.1016/s2352-3026(20)30210-6
发表时间：
2020-10
期刊：
The Lancet. Haematology
影响因子：
--
作者：
DiNardo CD;Maiti A;Rausch CR;Pemmaraju N;Naqvi K;Daver NG;Kadia TM;Borthakur G;Ohanian M;Alvarado Y;Issa GC;Montalban-Bravo G;Short NJ;Yilmaz M;Bose P;Jabbour EJ;Takahashi K;Burger JA;Garcia-Manero G;Jain N;Kornblau SM;Thompson PA;Estrov Z;Masarova L;Sasaki K;Verstovsek S;Ferrajoli A;Weirda WG;Wang SA;Konoplev S;Chen Z;Pierce SA;Ning J;Qiao W;Ravandi F;Andreeff M;Welch JS;Kantarjian HM;Konopleva MY
通讯作者：
Konopleva MY
影响因子：
51.1
作者：
Al-Sawaf, Othman;Zhang, Can;Fischer, Kirsten
通讯作者：
Fischer, Kirsten
影响因子：
20.3
作者：
Avet-Loiseau, Herve;Attal, Michel;Mathiot, Claire
通讯作者：
Mathiot, Claire
影响因子：
51.1
作者：
DiNardo, Courtney L.;Pratz, Keith W.;Pollyea, Daniel A.
通讯作者：
Pollyea, Daniel A.