Nowakowski Grzegorz S, Czuczman Myron S
From the Division of Hematology, Mayo Clinic, Rochester, MN; Roswell Park Cancer Institute, Buffalo, NY.
Am Soc Clin Oncol Educ Book. 2015:e449-57. doi: 10.14694/EdBook_AM.2015.35.e449.
Personalized therapy for the treatment of patients with cancer is rapidly approaching and is an achievable goal in the near future. A substantial number of novel targets have been developed into therapeutic agents. There is a substantial variability to antitumor activity by novel therapeutics because of the unique heterogeneity and biology that exists both between and within lymphoma subtypes. Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL). Approximately 40% of patients have refractory disease or disease that will relapse after an initial response, and the majority of patients with relapsed DLBCL will succumb to the disease. There are two major biologically distinct molecular subtypes of DLBCL: germinal center B-cell (GCB) and activated B-cell (ABC). ABC DLBCL is associated with substantially worse outcomes when treated with standard chemoimmunotherapy. In addition to GCB and ABC subtypes, double-hit lymphomas (approximately 5% to 10% of patients) and double-expressor lymphomas, which overexpress MYC and BCL2 protein, are aggressive DLBCLs and are also associated with a poor prognosis. Double-hit lymphomas have concurrent chromosomal rearrangements of MYC plus BCL2 (or less likely, BCL6). Advances in molecular characterization techniques and the development of novel agents targeting specific subtypes of DLBCL have provided a foundation for personalized therapy of DLBCL based on molecular subtype. A number of early clinical trials evaluating combinations of novel targeted agents with standard chemotherapy (R-CHOP) have been completed and have demonstrated the feasibility of this approach with encouraging efficacy. As such, molecular classification of DLBCL is not only important for prognostication, but moves to center stage for personalization of therapy for DLBCL.
癌症患者的个性化治疗正在迅速发展，并且在不久的将来是一个可以实现的目标。大量新靶点已被开发成治疗药物。由于淋巴瘤亚型之间和内部存在独特的异质性和生物学特性，新型治疗方法的抗肿瘤活性存在很大差异。弥漫性大B细胞淋巴瘤（DLBCL）是非霍奇金淋巴瘤（NHL）最常见的亚型。约40%的患者患有难治性疾病或初始缓解后会复发的疾病，大多数复发的DLBCL患者会死于该疾病。DLBCL有两种主要的生物学上不同的分子亚型：生发中心B细胞（GCB）和活化B细胞（ABC）。用标准化疗免疫疗法治疗时，ABC DLBCL的预后明显更差。除了GCB和ABC亚型外，双打击淋巴瘤（约占患者的5%至10%）和过表达MYC和BCL2蛋白的双表达淋巴瘤是侵袭性DLBCL，预后也较差。双打击淋巴瘤同时存在MYC和BCL2的染色体重排（或可能性较小的BCL6）。分子表征技术的进步以及针对DLBCL特定亚型的新型药物的开发为基于分子亚型的DLBCL个性化治疗提供了基础。一些评估新型靶向药物与标准化疗（R-CHOP）联合使用的早期临床试验已经完成，并证明了这种方法的可行性且疗效令人鼓舞。因此，DLBCL的分子分类不仅对预后评估很重要，而且在DLBCL治疗个性化方面占据了核心地位。
