Stephens Deborah M, Spurgeon Stephen E
Division of Hematology, Department of Internal Medicine, Huntsman Cancer Institute, The University of Utah, 2000 Circle of Hope, Room 4246, Salt Lake City, UT 84112, USA.
Division of Hematology and Medical Oncology, Department of Internal Medicine, Knight Cancer Institute at Oregon Health Sciences University, Portland, OR, USA.
Ther Adv Hematol. 2015 Oct;6(5):242-52. doi: 10.1177/2040620715592569.
Mantle cell lymphoma (MCL) is a rare subtype of non-Hodgkin's lymphoma typically marked by an aggressive clinical course and a predilection for relapse. The B-cell receptor (BCR) signaling survival pathway is chronically activated in MCL, contributing to its pathogenesis. Ibrutinib is an inhibitor of Bruton's tyrosine kinase, a vital component of this pathway. This article details the current clinical experience with ibrutinib in the treatment of patients with MCL, including completed and published clinical trials and reviews potential adverse events (AEs) and pitfalls associated with ibrutinib therapy. Although most AEs experienced by patients treated with ibrutinib are mild, some can be severe and treatment limiting and may be attributed to off-target effects. Ibrutinib is a very promising agent for patients with MCL with notable response rates. However, when used as a single agent, around one third of patients relapse in the first 2 years of treatment. Recently reported combination therapies have shown significant activity. Emerging data evaluating potential mechanisms of drug resistance and the poor clinical outcomes after treatment failure are also discussed. Further understanding of resistance and its implications not only in relapsed disease but in the frontline setting are needed. Investigation of strategies to overcome resistance remains an area of high unmet clinical need. Evaluation of the impact of shorter treatment duration, effects on minimal residual disease, and incorporation of novel combinations are also warranted.
套细胞淋巴瘤（MCL）是非霍奇金淋巴瘤的一种罕见亚型，通常以侵袭性临床病程和易于复发为特征。B细胞受体（BCR）信号存活通路在MCL中持续激活，促进其发病机制。伊布替尼是布鲁顿酪氨酸激酶的抑制剂，该激酶是此通路的重要组成部分。本文详细介绍了伊布替尼治疗MCL患者的当前临床经验，包括已完成和已发表的临床试验，并综述了与伊布替尼治疗相关的潜在不良事件（AE）和陷阱。尽管接受伊布替尼治疗的患者经历的大多数AE是轻度的，但有些可能很严重且限制治疗，可能归因于脱靶效应。伊布替尼对于MCL患者是一种非常有前景的药物，具有显著的缓解率。然而，作为单一药物使用时，约三分之一的患者在治疗的前两年复发。最近报道的联合疗法已显示出显著活性。还讨论了评估耐药性潜在机制和治疗失败后不良临床结局的新出现数据。需要进一步了解耐药性及其不仅在复发疾病中而且在一线治疗中的影响。克服耐药性策略的研究仍然是临床需求未得到满足的一个重要领域。评估较短治疗持续时间的影响、对微小残留病的作用以及纳入新的联合疗法也是必要的。
