曼地尔细胞淋巴瘤是一种B细胞非何杰金淋巴瘤（NHL），占所有NHL的2-6%，其特征是环D1的过度表达。过去十年中，在曼地尔细胞淋巴瘤领域出现了许多新的治疗方法，最显著的是布鲁顿酪氨酸激酶抑制剂（BTKi）类。BTKi在复发或难治曼地尔细胞淋巴瘤患者中显示出极佳的治疗效果，并正在研究其在一线治疗中的应用。然而，患者最终会因为抗药性的发展而进展。此外，这些患者的肿瘤微环境发生了改变，具有不同的生物学和治疗意义。因此，有必要探索在BTKi耐药患者中有效的新的治疗策略，或者可能规避抗药性。在本综述中，我们首先简要介绍BTKi，然后讨论BTK抵抗的各种机制，包括基因变异、癌细胞干细胞、肿瘤微环境和适应性重编程绕过BTK抑制作用，然后全面回顾了BTKi以外的目前和新兴的治疗选择，包括新型药物、CAR T细胞、双特异性抗体和抗体药物结合物。© 2023. 生物医学中央有限公司，施普林格自然出版集团的一部分。

Mantle cell lymphoma is a B cell non-Hodgkin lymphoma (NHL), representing 2-6% of all NHLs and characterized by overexpression of cyclin D1. The last decade has seen the development of many novel treatment approaches in MCL, most notably the class of Bruton's tyrosine kinase inhibitors (BTKi). BTKi has shown excellent outcomes for patients with relapsed or refractory MCL and is now being studied in the first-line setting. However, patients eventually progress on BTKi due to the development of resistance. Additionally, there is an alteration in the tumor microenvironment in these patients with varying biological and therapeutic implications. Hence, it is necessary to explore novel therapeutic strategies that can be effective in those who progressed on BTKi or potentially circumvent resistance. In this review, we provide a brief overview of BTKi, then discuss the various mechanisms of BTK resistance including the role of genetic alteration, cancer stem cells, tumor microenvironment, and adaptive reprogramming bypassing the effect of BTK inhibition, and then provide a comprehensive review of current and emerging therapeutic options beyond BTKi including novel agents, CAR T cells, bispecific antibodies, and antibody-drug conjugates.© 2023. BioMed Central Ltd., part of Springer Nature.