Nuvvula Sri, Dahiya Saurabh, Patel Shyam A
Department of Medicine - Division of Hematology/Oncology, University of Massachusetts Chan Medical School, UMass Memorial Medical Center, Worcester, MA.
Department of Medicine - Division of Hematology/Oncology, Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD.
Clin Lymphoma Myeloma Leuk. 2022 Jun;22(6):362-372. doi: 10.1016/j.clml.2021.11.010. Epub 2021 Nov 20.
Diffuse large B cell lymphoma (DLBCL) is an aggressive malignancy that has been traditionally treated with anthracycline-based chemotherapy, but approximately one-third of patients relapse after first-line therapy or have primary refractoriness. In this focused review, we discuss the 7 novel Food & Drug Administration (FDA)-approved medications for relapsed/refractory (R/R) DLBCL. We describe 5 CD19-targeted therapies, 3 of which are chimeric antigen receptor (CAR)-T cell therapies. We also highlight novel non-cell-based targeted therapies and discuss optimal sequencing considerations based on the goal of treatment, with an emphasis on CAR-T cell therapy as curative intent. We consider the limited tolerability of certain novel agents, prospects for elderly patients, and financial aspects of these approaches. We discuss advantages and limitations of these targeted therapies based on seminal clinical trials. Finally, we summarize ongoing trials involving promising agents making their way into the pharmacologic pipeline. These therapies include allogeneic CAR-T treatments and multi-antigen targeting therapies such as the CD19/CD22 CAR-T and the CD3/CD20 bispecific antibodies mosunetuzumab and odronextamab. We summarize our approach based on the best available evidence as we enter 2022.
弥漫性大B细胞淋巴瘤（DLBCL）是一种侵袭性恶性肿瘤，传统上采用基于蒽环类药物的化疗进行治疗，但约三分之一的患者在一线治疗后复发或存在原发性难治性。在本重点综述中，我们讨论了美国食品药品监督管理局（FDA）批准的7种用于复发/难治性（R/R）DLBCL的新型药物。我们描述了5种靶向CD19的疗法，其中3种是嵌合抗原受体（CAR）-T细胞疗法。我们还重点介绍了新型非细胞靶向疗法，并根据治疗目标讨论了最佳序贯考虑因素，重点是作为根治性手段的CAR-T细胞疗法。我们考虑了某些新型药物的耐受性有限、老年患者的前景以及这些治疗方法的经济方面。我们根据开创性的临床试验讨论了这些靶向疗法的优缺点。最后，我们总结了正在进行的涉及有望进入药物研发流程的药物的试验。这些疗法包括同种异体CAR-T治疗以及多抗原靶向疗法，如CD19/CD22 CAR-T和CD3/CD20双特异性抗体莫苏奈妥珠单抗和奥多司他单抗。随着我们进入2022年，我们根据现有最佳证据总结了我们的方法。
