Division of Blood Disorders, Section of Hematologic Malignancies, Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ, 08903, USA.
Curr Hematol Malig Rep. 2021 Feb;16(1):72-81. doi: 10.1007/s11899-021-00610-y. Epub 2021 Feb 22.
Diffuse large B cell lymphoma (DLBCL) is curable in a majority of patients; however, a significant portion of patients develop relapsed or refractory disease. High-dose chemotherapy followed by autologous stem cell transplant is the standard approach in appropriately selected patients. Many patients are not candidates for transplant and many who do receive autologous transplant relapse. Therapies which harness T cells including chimeric antigen receptor T cells (CAR-T) and bispecific antibodies are active in this chemotherapy-resistant population. We review the role of autologous and allogeneic stem cell transplant, CAR-T therapy, and bispecific antibodies in the treatment of relapsed or refractory DLBCL.
Phase I studies of bispecific antibodies directed against CD20 × CD3 have shown activity in heavily pre-treated DLBCL including in patients who have progressed following autologous transplant and/or CAR-T therapy. Two CAR-T products have received regulatory approval in relapsed or refractory DLBCL, with other products in clinical trials. CAR-T treatment has resulted in durable remissions and trials are ongoing to determine if CAR-T should replace autologous transplant as second-line therapy for DLBCL. The development of multiple T cell-directed therapies for DLBCL offers new treatment options for chemotherapy-resistant disease. We discuss our approach to relapsed or refractory DLBCL patients and the open question of optimal sequencing of autologous transplant (a current standard treatment), CAR-T therapy (FDA approved), and bispecific antibodies (in clinical trials).
弥漫性大 B 细胞淋巴瘤（DLBCL）在多数患者中可治愈；然而，仍有相当一部分患者出现复发或难治性疾病。在适当选择的患者中，大剂量化疗后自体造血干细胞移植是标准治疗方法。许多患者不适合进行移植，而许多接受自体移植的患者会复发。包括嵌合抗原受体 T 细胞（CAR-T）和双特异性抗体在内的利用 T 细胞的疗法在这种化疗耐药人群中具有活性。我们综述了自体和异基因造血干细胞移植、CAR-T 治疗以及双特异性抗体在治疗复发或难治性 DLBCL 中的作用。
针对 CD20×CD3 的双特异性抗体的 I 期研究显示，在包括在接受自体移植和/或 CAR-T 治疗后进展的患者在内的重度预处理 DLBCL 中具有活性。两种 CAR-T 产品已获得复发或难治性 DLBCL 的监管批准，其他产品正在临床试验中。CAR-T 治疗导致持久缓解，正在进行临床试验以确定 CAR-T 是否应替代自体移植作为 DLBCL 的二线治疗。针对 DLBCL 的多种 T 细胞导向疗法为化疗耐药疾病提供了新的治疗选择。我们讨论了我们对复发或难治性 DLBCL 患者的治疗方法，以及自体移植（目前的标准治疗）、CAR-T 疗法（FDA 批准）和双特异性抗体（临床试验）的最佳序贯的问题。
