Mantle cell lymphoma (MCL) is a subtype of non-Hodgkin lymphoma which is often characterised by a pattern of continued relapse after frontline chemoimmunotherapy. Although patients are usually able to regain durable disease control with covalent Bruton's tyrosine kinase inhibitors (cBTKi) at first relapse, it is now appreciated that such responses are often not sustained and the management of such patients represents a significant area of unmet need. There is an imperative to better understand resistance mechanisms and identify high-risk subsets of patients for whom cBTKi responses may be particularly short. Allogeneic stem cell transplant has an established role in appropriate candidates, however contemporary consensus is to preferentially offer chimeric antigen receptor (CAR) T-cell therapy. In this Review, we consider the available data on both existing and emerging treatment options, including non-covalent BTK inhibitors, bispecific antibodies, antibody-drug conjugates and Bcl-2 inhibitors and propose a treatment strategy prioritising clinical trials where available.

中文翻译：

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“黄金天气的终结”：共价 BTK 抑制剂复发或难治的套细胞淋巴瘤的治疗策略。


套细胞淋巴瘤 （MCL） 是非霍奇金淋巴瘤的一种亚型，其特征通常是一线化学免疫治疗后持续复发。尽管患者在首次复发时通常能够使用共价布鲁顿酪氨酸激酶抑制剂 （cBTKi） 恢复持久的疾病控制，但现在人们认识到，这种反应往往不会持续，并且此类患者的管理代表了未满足需求的重要领域。当务之急是更好地了解耐药机制并确定 cBTKi 反应可能特别短的高危患者亚群。同种异体干细胞移植在合适的候选者中具有既定的作用，但当代共识是优先提供嵌合抗原受体 （CAR） T 细胞疗法。在本综述中，我们考虑了有关现有和新兴治疗方案的现有数据，包括非共价 BTK 抑制剂、双特异性抗体、抗体-药物偶联物和 Bcl-2 抑制剂，并提出了一种治疗策略，在可用的情况下优先考虑临床试验。