文章：

基于抗体及其他新型药物在成人B细胞急性淋巴细胞白血病中的应用

Antibody-Based and Other Novel Agents in Adult B-Cell Acute Lymphoblastic Leukemia

原文发布日期：25 February 2025

DOI: 10.3390/cancers17050779

类型: Article

开放获取: 是

英文摘要：

Despite notable progress in managing B-cell acute lymphoblastic leukemia (B-ALL) over recent decades, particularly in pediatric cohorts where the 5-year overall survival (OS) reaches 90%, outcomes for the 10–15% with relapsed and refractory disease remain unfavorable. This disparity is further accentuated in adults, where individuals over the age of 40 years undergoing aggressive multiagent chemotherapy continue to have lower survival rates. While the adoption of pediatric-inspired treatment protocols has enhanced complete remission (CR) rates among younger adults, 20–30% of these patients experience relapse, resulting in a subsequent 5-year OS rate of 40–50%. For relapsed B-ALL in adults, there is no universally accepted standard salvage therapy, and the median OS is short. The cornerstone of B-ALL treatment continues to be the utilization of combined cytotoxic chemotherapy regimens to maximize early and durable disease control. In this manuscript, we go beyond the multiagent chemotherapy medications developed prior to the 1980s and focus on the incorporation of antibody-based therapy for B-ALL with an eye on existing and upcoming approved indications for blinatumomab, inotuzumab ozogamicin, other monoclonal antibodies, and chimeric antigen receptor (CAR) T cell products in frontline and relapsed/refractory settings. In addition, we discuss emerging investigational therapies that harness the therapeutic vulnerabilities of the disease through targeting apoptosis, modifying epigenetics, and inhibiting the mTOR pathway.

摘要翻译： 

尽管近几十年来B细胞急性淋巴细胞白血病（B-ALL）的治疗取得了显著进展，尤其在儿童患者中5年总生存率已达到90%，但仍有10-15%的复发难治性患者预后不佳。这种差异在成人患者中更为突出，40岁以上接受强化多药化疗的患者生存率持续偏低。虽然采用儿童启发式治疗方案提高了年轻成人患者的完全缓解率，但其中20-30%的患者仍会出现复发，导致后续5年总生存率仅为40-50%。对于成人复发B-ALL，目前尚无公认的标准挽救治疗方案，且中位总生存期较短。B-ALL治疗的基石仍然是联合细胞毒性化疗方案，以实现早期和持久的疾病控制。本文不仅回顾了1980年代前开发的多药化疗方案，更聚焦于B-ALL抗体疗法的整合应用，重点关注贝林妥欧单抗、奥加伊妥珠单抗、其他单克隆抗体以及嵌合抗原受体T细胞产品在新诊断和复发/难治性治疗场景中现有及即将获批的适应症。此外，我们还探讨了通过靶向细胞凋亡、表观遗传修饰和抑制mTOR通路等针对疾病治疗弱点的前沿研究性疗法。

原文链接：

Antibody-Based and Other Novel Agents in Adult B-Cell Acute Lymphoblastic Leukemia