Thomas Colin J, Carvajal Veronica, Barta Stefan K
Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cancers (Basel). 2024 May 20;16(10):1937. doi: 10.3390/cancers16101937.
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.
套细胞淋巴瘤（MCL）是一种罕见的、异质性的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，且常对化疗耐药，这进一步凸显了新型无化疗治疗方案的必要性。在过去十年中，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治疗格局。在此，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过程的靶向无化疗治疗的出现。在讨论其临床数据和毒性时，针对核因子κB（NF-κB）的组成性激活、布鲁顿酪氨酸激酶信号传导和抗凋亡的治疗将是主要关注点。我们的综述还将主要关注靶向治疗在复发/难治性情况下的出现和应用，但也会讨论其在一线治疗以及与其他药物联合使用方面的出现情况。
