套细胞淋巴瘤的靶向治疗。
Targeted Therapies in the Treatment of Mantle Cell Lymphoma.
发表日期:2024 May 20
作者:
Colin J Thomas, Veronica Carvajal, Stefan K Barta
来源:
Cancers
摘要:
套细胞淋巴瘤 (MCL) 是一种罕见的异质性 B 细胞非霍奇金淋巴瘤。标准的一线治疗采用化疗,通常随后进行自体造血细胞移植巩固治疗;然而,在大多数患者中,淋巴瘤会复发并需要后续治疗。此外,套细胞淋巴瘤主要影响老年患者,并且经常对化疗产生耐药性,这进一步促进了新的无化疗治疗选择的必要性。在过去的十年中,随着治疗模式进一步远离主要依赖细胞毒性药物,套细胞淋巴瘤的靶向治疗已经改变了实践。在这里,我们将回顾套细胞淋巴瘤的病理生理学,并讨论旨在破坏驱动其淋巴瘤发生的异常生物学的靶向、无化疗治疗的出现。当我们讨论其临床数据和毒性时,针对 NF-kB 组成型激活、布鲁顿酪氨酸激酶信号传导和抗凋亡的治疗将成为主要焦点。我们的综述还将主要关注复发/难治性情况下靶向治疗的出现和使用,但也会讨论其在一线治疗中的使用以及与其他药物联合使用的出现。
Mantle cell lymphoma (MCL) is a rare, heterogeneous B-cell non-Hodgkin's lymphoma. The standard front-line treatment utilizes chemotherapy, often followed by consolidation with an autologous hematopoietic cell transplant; however, in most patients, the lymphoma will recur and require subsequent treatments. Additionally, mantle cell lymphoma primarily affects older patients and is frequently chemotherapy-resistant, which has further fostered the necessity for new, chemotherapy-free treatment options. In the past decade, targeted therapies in mantle cell lymphoma have been practice-changing as the treatment paradigm shifts further away from relying primarily on cytotoxic agents. Here, we will review the pathophysiology of mantle cell lymphoma and discuss the emergence of targeted, chemotherapy-free treatments aimed at disrupting the abnormal biology driving its lymphomagenesis. Treatments targeting the constitutive activation of NF-kB, Bruton's Tyrosine Kinase signaling, and anti-apoptosis will be the primary focus as we discuss their clinical data and toxicities. Our review will also focus primarily on the emergence and use of targeted therapies in the relapsed/refractory setting but will also discuss the emergence of their use in front-line therapy and in combination with other agents.