Kleber Martina, Ntanasis-Stathopoulos Ioannis, Terpos Evangelos
Department of Internal Medicine, Clinic Hirslanden Zurich, 8032 Zurich, Switzerland.
Faculty of Medicine, University of Basel, 4031 Basel, Switzerland.
Cancers (Basel). 2023 Dec 13;15(24):5829. doi: 10.3390/cancers15245829.
Multiple myeloma (MM) represents a hematological neoplasia with an uncontrolled proliferation of malignant plasma cells and complex cytogenetic abnormalities. t(11;14) has emerged as a crucial genetic aberration and is one of the most common primary translocations in MM. Patients harboring t(11;14) represent a distinctive subgroup with a clinical profile that differs from t(11;14)-negative MM risk categories. One of the key features linked with t(11;14) is the BCL2 dependency, indicating vulnerability to BCL2 inhibition. BCL2 inhibitors, such as venetoclax, demonstrated impressive efficacy alone or in combination with other anti-myeloma drugs in patients with RRMM accompanied by t(11;14) and BCL2 overexpression. Therefore, t(11;14) plays a key role in both risk stratification and informed decision making towards a tailored therapy. In this review, we highlight the biology of t(11;14) in MM cells, summarize the current evolving role of t(11;14) in the era of novel agents and novel targeted therapies, illuminate current efficacy and safety data of BCL2-based treatment options and explore the future prospects of individualized precision medicine for this special subgroup of patients with MM.
多发性骨髓瘤(MM)是一种血液系统肿瘤,其特征为恶性浆细胞不受控制地增殖以及复杂的细胞遗传学异常。t(11;14)已成为一种关键的基因畸变,是MM中最常见的原发性易位之一。携带t(11;14)的患者代表了一个独特的亚组,其临床特征与t(11;14)阴性的MM风险类别不同。与t(11;14)相关的关键特征之一是对BCL2的依赖性,这表明对BCL2抑制敏感。BCL2抑制剂,如维奈克拉,在伴有t(11;14)和BCL2过表达的复发/难治性MM(RRMM)患者中单独使用或与其他抗骨髓瘤药物联合使用时,显示出令人印象深刻的疗效。因此,t(11;14)在风险分层以及针对个体化治疗的明智决策中均起着关键作用。在本综述中,我们重点介绍MM细胞中t(11;14)的生物学特性,总结t(11;14)在新型药物和新型靶向治疗时代不断演变的作用,阐明基于BCL2的治疗方案的当前疗效和安全性数据,并探索针对这一特殊MM患者亚组的个体化精准医学的未来前景。