Agarwal Rishu, Dawson Mark A, Dreyling Martin, Tam Constantine S
a Division of Cancer Research , Peter MacCallum Cancer Centre , Melbourne , Victoria , Australia.
b Sir Peter MacCallum Department of Oncology , University of Melbourne , Melbourne , Victoria , Australia.
Leuk Lymphoma. 2018 Dec;59(12):2769-2781. doi: 10.1080/10428194.2018.1457148. Epub 2018 Jun 18.
Novel targeted therapeutics has significantly improved the outlook of patients with relapsed/refractory mantle cell lymphoma (R/R MCL). Despite significant efficacy, one of the major limitations of these targeted agents is presence of primary or acquired resistance to these novel drugs. Patients who fail primary therapy especially with ibrutinib have poor outcomes and may respond poorly to subsequent therapies. Hence, it is important to understand resistance mechanisms a priori to identify patients who are unlikely to respond, and to explore alternative therapeutic strategies. In this review, we will discuss the currently most active two drugs: ibrutinib and venetoclax, both of which have shown high response rates in R/R MCL. We review current understanding of genomic alterations associated with resistance, and discuss possible strategies to overcome these resistance mechanisms.
新型靶向疗法显著改善了复发/难治性套细胞淋巴瘤（R/R MCL）患者的预后。尽管这些靶向药物疗效显著，但其主要局限性之一是对这些新药存在原发性或获得性耐药。初始治疗失败尤其是对依鲁替尼治疗失败的患者预后较差，对后续治疗的反应可能也不佳。因此，预先了解耐药机制对于识别不太可能有反应的患者以及探索替代治疗策略非常重要。在本综述中，我们将讨论目前最有效的两种药物：依鲁替尼和维奈克拉，这两种药物在R/R MCL中均显示出高缓解率。我们回顾了目前对与耐药相关的基因组改变的认识，并讨论了克服这些耐药机制的可能策略。
