Chronic lymphocytic leukemia in 2020: a surfeit of riches?
Chronic lymphocytic leukemia in 2020: a surfeit of riches?
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DOI：
10.1038/s41375-020-0852-7
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发表时间：
2020-08
期刊：
影响因子：
11.4
通讯作者：
Kay NE
中科院分区：
文献类型：
--
作者：
Parikh SA;Gale RP;Kay NE
自20世纪40年代以来美国食品和药物管理局(FDA)批准的治疗慢性淋巴细胞白血病(CLL)的药物如图1所示。化疗时代最初以氯氨丁苯为主，然后是20世纪90年代初的氟达拉滨和五氧他汀类嘌呤核苷类似物，其中包括强的松、环磷酰胺。1997年利妥昔单抗的引入开启了化学免疫治疗(CIT)的时代，在CIT时代，与氟达拉滨、环磷酰胺和利妥昔单抗(FCR)的联合治疗导致约40%的先前未经治疗的CLL患者完全缓解(CR)，而具有突变的免疫球蛋白重链(IGHV)基因的患者则长期无进展生存(PFS)。然而，对于通过荧光原位杂交(FISH)、TP53突变或复杂细胞遗传学检测到的Del(17p)或Del(11q)等高危疾病患者，FCR的疗效较差。从2009年开始，FDA已经批准了六种新药，用于初级治疗和晚期疾病。虽然这些药物对有不良预后协变量的患者有效，但这些新批准的药物存在几个问题，包括：(1)没有治愈方法；(2)导致管理挑战的新不良事件；以及(3)由于需要长期治疗而造成的沉重经济负担。
Drugs approved by the US Food and Drug Administration (FDA) for therapy of chronic lymphocytic leukemia (CLL) since the 1940s are displayed in Fig. 1. The chemotherapy era was dominated initially by chlorambucil with or without prednisone, cyclophosphamide followed by purine nucleoside analogs such as fludarabine and pentostatin in the early 1990s. The introduction of rituximab in 1997 started the era of chemo-immunotherapy (CIT) in which combination therapy with fludarabine, cyclophosphamide, and rituximab (FCR) resulted in complete remission (CR) in about 40% of previously untreated persons with CLL—with long progression-free survival (PFS) in those with mutated immunoglobulin heavy chain (IGHV) genes. However, FCR had poor efficacy in persons with high-risk disease such as del (17p) or del (11q) detected by fluorescence in situ hybridization (FISH), TP53 mutation or complex cytogenetics [1]. Starting in 2009, six new drugs have been approved by the FDA for both initial therapy and for advanced disease. Although these drugs are active in persons with adverse prognostic co-variates, there are several issues with these new approvals including:(1) no cures;(2) new adverse events resulting in management challenges; and (3) high economic burden because of the need for prolonged therapy.
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影响因子：
10.1
作者：
Mato AR;Nabhan C;Thompson MC;Lamanna N;Brander DM;Hill B;Howlett C;Skarbnik A;Cheson BD;Zent C;Pu J;Kiselev P;Goy A;Claxton D;Isaac K;Kennard KH;Timlin C;Landsburg D;Winter A;Nasta SD;Bachow SH;Schuster SJ;Dorsey C;Svoboda J;Barr P;Ujjani CS
通讯作者：
Ujjani CS
影响因子：
20.3
作者：
Hallek, Michael;Cheson, Bruce D.;Kipps, Thomas J.
通讯作者：
Kipps, Thomas J.
影响因子：
168.9
作者：
Hallek, M.;Fischer, K.;Stilgenbauer, S.
通讯作者：
Stilgenbauer, S.
影响因子：
11.4
作者：
Ghia, Paolo;Rawstron, Andy
通讯作者：
Rawstron, Andy
未治疗的慢性淋巴细胞性白血病患者的骨髓造血功能障碍。
影响因子：
11.4
作者：
Manso BA;Zhang H;Mikkelson MG;Gwin KA;Secreto CR;Ding W;Parikh SA;Kay NE;Medina KL
通讯作者：
Medina KL