ABSTRACT

Introduction

Approximately, a third of patients with diffuse large B-cell lymphoma (DLBCL) have refractory or relapsed disease after initial treatment. Despite recent regulatory approval of several new agents, including CAR-T cell therapy, polatuzumab vedotin and tafasitamab, there is still a need for additional therapies that expand the therapeutic alternatives and improve outcomes for patients with DLBCL that progresses after first line therapy.

Areas covered

Studies of recently approved agents for relapsed DLBCL are reviewed. The relevance of CD19 as an immunotherapeutic target. The pharmacologic composition of loncastuximab tesirine and its cytotoxic payload, a pyrrolobenzodiazepine dimer. Phase I and phase 2 data for loncastuximab tesirine in non-Hodgkin lymphoma, showing the safety profile of this drug and the emerging efficacy results in DLBCL.

Expert opinion

Loncastuximab tesirine is an antiCD19 antibody drug conjugate with a novel cytotoxic payload. Early studies showed this drug is tolerable, with a safety profile that is different from other antibody drug conjugates approved for lymphoid malignancies. Efficacy data shows activity in different non-Hodgkin lymphoma entities, and a phase 2 study has been completed in DLBCL showing durable responses, including in high-risk subgroups. Loncastuximab tesirine will be an important addition to the treatment alternatives for DLBCL.

中文翻译：

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Loncastuximab tesirine 用于治疗复发或难治性弥漫性大 B 细胞淋巴瘤

摘要

介绍

大约三分之一的弥漫性大 B 细胞淋巴瘤 (DLBCL) 患者在初始治疗后出现难治性或复发性疾病。尽管最近监管部门批准了几种新药物，包括 CAR-T 细胞疗法、polatuzumab vedotin 和 tafasitamab，但仍然需要其他疗法来扩大治疗选择并改善一线治疗后进展的 DLBCL 患者的预后。

涵盖的领域

回顾了最近批准的复发性 DLBCL 药物的研究。CD19 作为免疫治疗靶点的相关性。loncastuximab tesirine 的药理成分及​​其细胞毒性有效载荷，即吡咯并苯二氮卓二聚体。loncastuximab tesirine 在非霍奇金淋巴瘤中的 I 期和 2 期数据，显示了该药物的安全性以及在 DLBCL 中出现的疗效结果。

专家意见

Loncastuximab tesirine 是一种具有新型细胞毒性有效载荷的抗 CD19 抗体药物偶联物。早期研究表明，这种药物是可以耐受的，其安全性不同于其他批准用于淋巴恶性肿瘤的抗体药物偶联物。疗效数据显示在不同的非霍奇金淋巴瘤实体中的活性，并且在 DLBCL 中完成的 2 期研究显示持久反应，包括在高风险亚组中。Loncastuximab tesirine 将成为 DLBCL 治疗替代方案的重要补充。