Lymphoma Service, Memorial Sloan Kettering Cancer Center, NY, USA.
Department of Clinical Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Kraków, Poland.
Expert Opin Biol Ther. 2021 Apr;21(4):455-463. doi: 10.1080/14712598.2021.1884677. Epub 2021 Feb 15.
Patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) require further treatment options, especially in cases that cannot tolerate stem cell transplant or cytotoxic chemotherapy. CD19 has emerged as an attractive target in B-cell malignancy and is the subject of several therapeutic strategies. The anti-CD19, humanized, monoclonal antibody tafasitamab (MOR208) has an engineered, modified Fc region with increased affinity for Fcγ receptors, leading to increased cytotoxicity via natural killer cells and macrophages (antibody-dependent cellular cytotoxicity and antibody-dependent cell-mediated phagocytosis) in a promising approach.
The development of tafasitamab is reviewed, together with the pharmacokinetics and clinical experience of tafasitamab in R/R DLBCL; clinical data have led to FDA approval and inclusion in NCCN treatment guidelines for tafasitamab in combination with lenalidomide in this indication.
Patients with R/R DLBCL who have failed rituximab-containing regimens may be resistant to CD20-directed therapies; therefore, therapies with an alternative mode of action are of great interest in this setting. Tafasitamab, an anti-CD19 monoclonal antibody, in combination with lenalidomide has demonstrated promising efficacy for patients with R/R DLBCL who are ineligible for autologous stem cell transplantation. This could provide an alternative approach to classical chemotherapy-based regimens in the relapsed setting.
复发或难治性弥漫性大 B 细胞淋巴瘤(R/R DLBCL)患者需要进一步的治疗选择,特别是在不能耐受干细胞移植或细胞毒性化疗的情况下。CD19 已成为 B 细胞恶性肿瘤的一个有吸引力的靶点,是几种治疗策略的研究对象。抗 CD19、人源化、单克隆抗体 tafasitamab(MOR208)具有经过工程改造的、修饰的 Fc 区,与 Fcγ 受体的亲和力增加,导致自然杀伤细胞和巨噬细胞(抗体依赖的细胞毒性和抗体依赖的细胞吞噬作用)的细胞毒性增加,这是一种很有前途的方法。
本文回顾了 tafasitamab 的开发,以及 tafasitamab 在 R/R DLBCL 中的药代动力学和临床经验;临床数据导致 FDA 批准,并将 tafasitamab 纳入 NCCN 治疗指南,与来那度胺联合用于该适应症。
接受含利妥昔单抗方案治疗后复发的 R/R DLBCL 患者可能对 CD20 靶向治疗耐药;因此,在这种情况下,具有替代作用模式的治疗方法非常有意义。抗 CD19 单克隆抗体 tafasitamab 与来那度胺联合治疗不适合自体干细胞移植的 R/R DLBCL 患者显示出良好的疗效。这可能为复发时的经典基于化疗的方案提供了一种替代方法。