2023年第17届恶性淋巴瘤（ICML）国际会议正在瑞士·卢加诺盛大举行。Alexander Fosså教授在“关注大B细胞，双重打击淋巴瘤”专题会议中，带来了“Zilovertamab vedotin（MK-2140）治疗复发或难治性（R/R）弥漫性大B细胞淋巴瘤（DLBCL）：Ⅱ期开放标签，waveLINE-004研究”的精彩报告。《肿瘤瞭望》在会议现场对Fosså教授进行了第一时间采访。

 

Fosså教授：对于R/R DLBCL，我们从分子层面对其亚型有了深入的认识，但尚未发现有合适的治疗靶点。CAR-T疗法和双特异性抗体（bi-specific antibodies）是目前研究的重点，不过仍有大量患者不适用该疗法或者对治疗无反应。因此，除了一些目前已在应用中的靶点外，我们也在探索其他潜在靶点，如血液系统肿瘤表面的ROR1抗原。

 

Oncology Frontier：Because of its high heterogeneity，DLBCL is divided into many subtypes，and the response of each histological type to treatment is different.What is the current treatment status of DLBCL?

 

If you were talking about relapsed and refractory，diffuse large piece lymphoma，we have molecular insights into these subtypes of the lymphoma.But none of them have given us any good targets.We are focusing on CAR-T and bi-specific antibodies，but also for a great number of patients，these will either be not possible to perform，or the patients will not respond to them.So therefore，new targets，apart from those that we are already using，are interesting.And the that’s why we think the ROR1 antigen on the surface of haematological malignancy is an interesting target.

 

Fosså教授：除CAR-T细胞和双特异性抗体的相关靶点外，我们在探索其他治疗靶点时，ROR1是一个有意思的发现。ROR1是一种表面抗原，在大多数DLBCL患者中表达，同时它还是一种在其他任何成人正常组织中都不表达的肿瘤胚胎蛋白。这也是为什么由Merck公司开发的ROR1抗体偶联药物（ADC）广受关注。我们为那些不符合自体移植和CAR-T治疗条件或治疗失败的患者，开展了一项典型Ⅱ期研究。研究目前尚处于起步阶段，本次会议上我们汇报了前40名患者的临床数据。

 

Oncology Frontier：An oral study reported by your team about waveLINE-004 study in this meeting.Could you please introduce this study in detail?

 

Yeah，it comes from our interest to look at other targets than those there are addressed by CAR-T cells and bi-specific antibodies.It’s expressed on a large number of diffuse，large B-celllymphoma patients.It’s a surface antigen.It’s an onco-fetoprotein that is not expressed on any other adult normal tissues.That’s why an antibody drug conjugate that has been developed by Merck is an interesting target to go for.We developed a typical phase two study for patients that had either been ineligible or had really failed to respond to autologous transplant and CAR-T cells.It’s just started.So we are reporting here on this meeting，the experience in the first 40 patients.

 

Fosså教授：ROR1是一个有趣的靶点，因为它不是通过CAR-T细胞和特定抗体处理的典型靶点。ROR1是一个肿瘤特异性靶点，在DLBCL和套细胞淋巴瘤中都有表达。它或许可以用以结合或取代B细胞特异性标志物。另外，还可以看看ROR1是否参与到其他类型的淋巴瘤中，如T细胞淋巴瘤。因此，它在血液肿瘤学中有着其他靶点所不具备的应用前景。

 

Oncology Frontier：ROR1 has good anti-tumor activity and controllable safety in relapse and refractory DLBCL patients，which is an ideal target for anti-tumor drugs.Could you share the prospect of ROR1 in the field of hematological oncology?

 

It is an interesting target，because it’s not the typical target that we address by CAR-T cells and by specific antibodies.It’s a completely tumor specific target，and it’s expressed not only on defuse large B-celllymphomas，but also evidently in mantle cell lymphomas.And that’s why we believe this could be an interesting，additional target to either be combined or to replace many of the things that we do with the B cell specific markers.It would also be interesting to see if it could be involved into other kinds of lymphomas such as T cell lymphomas.It holds prospects that other targets in haemato-oncology do not have.

 

Alexander Fosså教授

挪威奥斯陆大学医院肿瘤科医生，擅长淋巴瘤、血液系统疾病以及干细胞移植等。