不适合移植的大 B 细胞淋巴瘤二线使用 axicabtagene ciloleucel:ALYCANTE 最终分析
Second-line axicabtagene ciloleucel in large B-cell lymphoma ineligible for transplantation: ALYCANTE final analysis.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Monoclonal Antibodies in the Treatment of Diffuse Large B-Cell Lymphoma: Moving beyond Rituximab.
Monoclonal Antibodies in the Treatment of Diffuse Large B-Cell Lymphoma: Moving beyond Rituximab.
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利妥昔单抗虽彻底改变了弥漫性大B细胞淋巴瘤(DLBCL)的治疗,但相当一部分患者仍出现难治性疾病,或在治疗结束后早期复发。复发/难治(R/R)患者缺乏有效治疗选择,预后因而较差。新型抗CD20抗体曾引发的初期热情很快消退,因为这些药物未能证明优于利妥昔单抗。
因此,研究重点转向开发作用机制独特的新药。其中,两种抗体药物偶联物——维泊妥珠单抗维多汀(PolaV)和loncastuximab tesirine,以及一种抗CD19生物工程抗体tafasitamab,已获批用于R/R DLBCL。PolaV已获美国FDA和欧洲药品管理局(EMA)批准,而loncastuximab tesirine和tafasitamab尚未获EMA批准。随机试验结果及PolaV真实世界数据均令人鼓舞。通过CD3阳性T细胞与CD20连接的双特异性抗体等新药,在临床试验中显示出很有前景的结果,预计不久将获批用于R/R DLBCL。随着DLBCL治疗手段不断扩展,R/R患者生存改善和治愈率提高有望很快显现。
Although rituximab has revolutionized the treatment of diffuse large B-cell lymphoma (DLBCL), a significant proportion of patients experience refractory disease or relapse early after the end of treatment. The lack of effective treatment options in the relapsed/refractory (R/R) setting had made the prognosis of these patients dismal. The initial enthusiasm for novel anti-CD20 antibodies had been short-lived as they failed to prove their superiority to rituximab.
Therefore, research has focused on developing novel agents with a unique mechanism of action. Among them, two antibody-drug conjugates, namely polatuzumab vedotin (PolaV) and loncastuximab tesirine, along with tafasitamab, an anti-CD19 bioengineered antibody, have been approved for the treatment of R/R DLBCL. Whereas PolaV has been FDA and EMA approved, EMA has not approved loncastuximab tesirine and tafasitamab yet.
Results from randomized trials, as well as real-life data for PolaV have been promising. Novel agents as bispecific antibodies bridging CD3 on T-cells to CD20 have shown very promising results in clinical trials and are expected to gain approval for treatment of R/R DLBCL soon. As the therapeutic armamentarium against DLBCL is expanding, an improvement in survival of patients with R/R and higher cure rates might soon become evident.
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