Fakhri Bita, Ai Weiyun
Division of Hematology and Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Ther Adv Hematol. 2021 Oct 8;12:20406207211048959. doi: 10.1177/20406207211048959. eCollection 2021.
Previously considered a subtype of diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL) is now recognized by the World Health Organization as an independent entity. PMBCL has clinicopathologic features that are separate from systemic DLBCL and harbors some biologic characteristics which overlap with nodular sclerosing classic Hodgkin's lymphoma (cHL). Similar to cHL, copy number alterations of 9p24.1 are frequently seen in PMBCL, which leads to increased expression of key genes in the region, including programmed death-ligand 1( PD-L1), PD-L2, and JAK2. In addition, PMBCL cells express CD30 in a mostly patchy fashion. In the upfront setting, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (i.e., DA-EPOCH-R) is the only regimen that has been shown in a prospective setting to result in outstanding outcomes without consolidative radiation to the mediastinum, with a 5-year event-free survival rate of 93% and overall survival rate of 97%. Thus, in recent years, DA-EPOCH-R has been recognized as the preferred frontline regimen. Despite the encouraging results in the frontline setting, the outcomes in the relapsed/refractory setting remain poor. The current approach of salvage chemotherapy followed by autologous stem cell transplantation, as used in patients with DLBCL, does not result in high rates of cure in patients with rrPMBCL. In recent years, the characteristic molecular features identified in PMBCL have provided more treatment opportunities for this patient population. In the relapsed setting, single-agent PD-1 inhibitor pembrolizumab have demonstrated high and durable remission rates. Despite the expression of CD30, the CD30 antibody drug-conjugate brentuximab vedotin (BV) as a single agent has been deemed inactive in this disease. On the contrary, the combinations of BV and PD-1 inhibitor have shown higher response rates than PD-1 inhibitor alone. Moreover, anti-CD19 chimeric antigen receptor T-cell (CAR T-cell) therapy has been positioned as another successful strategy for patients with rrPMBCL. Axicabtagene ciloleucel and lisocabtagene maraleucel are two products used in rrPMBCL.
原发性纵隔B细胞淋巴瘤（PMBCL）曾被认为是弥漫性大B细胞淋巴瘤（DLBCL）的一种亚型，现在世界卫生组织将其认定为一个独立的实体。PMBCL具有与系统性DLBCL不同的临床病理特征，并且具有一些与结节硬化型经典霍奇金淋巴瘤（cHL）重叠的生物学特性。与cHL相似，9p24.1的拷贝数改变在PMBCL中经常可见，这导致该区域关键基因的表达增加，包括程序性死亡配体1（PD-L1）、PD-L2和JAK2。此外，PMBCL细胞大多呈斑片状表达CD30。在初始治疗中，剂量调整的依托泊苷、泼尼松、长春新碱、环磷酰胺、多柔比星和利妥昔单抗（即DA-EPOCH-R）是唯一一种在前瞻性研究中被证明能在不进行纵隔巩固放疗的情况下取得出色疗效的方案，5年无事件生存率为93%，总生存率为97%。因此，近年来，DA-EPOCH-R已被公认为首选的一线方案。尽管在一线治疗中取得了令人鼓舞的结果，但复发/难治性患者的治疗结果仍然很差。目前用于DLBCL患者的挽救化疗后自体干细胞移植方法，在复发/难治性PMBCL（rrPMBCL）患者中并不能带来高治愈率。近年来在PMBCL中发现的特征性分子特征为该患者群体提供了更多的治疗机会。在复发情况下，单药PD-1抑制剂帕博利珠单抗已显示出高且持久的缓解率。尽管有CD30的表达，但CD30抗体药物偶联物本妥昔单抗（BV）作为单药在这种疾病中被认为无效。相反，BV与PD-1抑制剂的联合使用显示出比单独使用PD-1抑制剂更高的缓解率。此外，抗CD19嵌合抗原受体T细胞（CAR T细胞）疗法已被定位为rrPMBCL患者的另一种成功策略。阿基仑赛和瑞基奥仑赛是用于rrPMBCL的两种产品。
