编者按：外周T细胞淋巴瘤（PTCL）是一组罕见但极具异质性的血液恶性肿瘤，大多呈高度侵袭性、疾病进展迅速，现有治疗手段疗效不理想，整体预后较差。近日中国临床肿瘤学会（CSCO）白血病专家委员会、淋巴瘤专家委员会及骨髓瘤筹备委员会工作会议暨2024年CSCO血液及淋巴瘤、骨髓瘤疾病学术大会圆满举行，会后《肿瘤瞭望-血液时讯》特邀美国淋巴瘤联盟主席/弗吉尼亚大学癌症中心Owen O’Connor教授分享PTCL研究进展及参会感悟。
《肿瘤瞭望-血液时讯》能否请您分享下参加CSCO血液学术大会的感受？
Owen O'Connor教授：这些年来，我有幸参加过几次CSCO会议，大会给我留下了深刻印象。大会规模引人瞩目，聚集了来自中国各地以及各个血液肿瘤领域的专业医生。大会报道了多项最新进展，包括CAR-T细胞疗法、抗体偶联药物及双特异性抗体类药物等等，中国在血液肿瘤治疗的创新发展正在取得飞速进步。CSCO学术委员会聚集了全国各地的医学精英及科研学者，对于促进学术经验和临床能力的交流沟通具有重要贡献。大会围绕T细胞淋巴瘤新药治疗设立了多场讲座及讨论，以促进协作创新，优化患者治疗方案。
Oncology Frontier-Hematology Frontier: Dr. Owen O'Connor, could you please share your thoughts on attending the CSCO Academic?
Dr. Owen O'Connor: Yes, I've had the privilege of attending several CSCO meetings over the years, and I must say I've been consistently impressed. One aspect that stands out is the presence of numerous dedicated physicians from all across China, specializing in various aspects of blood cancers. China is making remarkable strides in terms of innovation in blood cancer treatments, spanning from the latest in CAR T-cell therapy to cutting-edge antibodies and bispecifics. The CSCO Academic serves as an invaluable platform to unite medical professionals and scientists from across the nation, facilitating the exchange of experiences and insights. Many of the lectures and discussions have revolved around new drugs for treating T cell lymphoma, making it immensely satisfying to witness the collaborative efforts aimed at optimizing therapies for these challenging blood cancers.
《肿瘤瞭望-血液时讯》：本次会议上您分享了PTCL治疗进展相关内容。能否请您详细介绍下近年来的PTCL治疗进展，以及您如何看待PTCL诊疗的未来发展方向？
Owen O'Connor教授：PTCL是一组罕见但极具异质性的血液恶性肿瘤。对于B细胞恶性肿瘤而言，我们已取得了实质性进展；但对于PTCL的自然病程进展，目前仍有许多未知。几十年来，我们主要依靠化疗联合策略治疗PTCL，而新药研究也常常带给我们新的治疗希望；遗憾的是，这种方案常常导致毒性增加，但患者结局却并未得到实质性改善。在这种情况下，我们需要重新评估既往的治疗策略和未来前景。
目前，我们已拥有多种靶向PTCL特异性生物学特征的创新药物，并且合理联合治疗可能会具有良好疗效；其中并不包含化疗方案，因为目前研究重点已转向开发无化疗方案。由于PTCL存在表观遗传生物学功能严重失调，而某些药物可以有效地改善这种情况。PTCL未来的诊疗策略包括新药联合使用策略、无化疗方案以及免疫联合治疗等。通过这些治疗方案，我们有望改善PTCL自然进程。
Oncology Frontier-Hematology Frontier: In this meeting, you presented a remarkable report on advancing the treatment of PTCL. Could you elaborate on the significant progress in PTCL treatment in recent years, and how do you envision the future treatment direction for PTCL?
Dr. Owen O'Connor: Certainly. PTCL presents a unique challenge in the land scape of blood cancers. Unlike B-cell malignancies, where we've made substantial progress, PTCL has remained relatively resistant to change in its natural course. For decades, we have primarily relied on combination chemotherapy for PTCL, often incorporating new drugs with the hope of witnessing a breakthrough. Regrettably, this approach has often resulted in increased toxicity without substantial improvements in outcomes. We now stand at a critical juncture, necessitating a reevaluation of our past strategies and an innovative outlook.
We have at our disposal a range of novel drugs that target specific biologic features of PTCL, with promising results when combined judiciously, but not with chemotherapy. The focus has shifted toward developing chemotherapy-free regimens, acknowledging that PTCL possesses unique epigenetic dysregulations that can be effectively targeted by certain drugs. The future appears to involve a synergy of new drugs, free from the constraints of chemotherapy, and the exploration of complementary immunologic therapies. This combined approach holds the most promise for altering the natural course of PTCL.
《肿瘤瞭望-血液时讯》：您认为在过去的一年中，淋巴瘤的诊断和治疗还有哪些令人瞩目的研究进展？
Owen O'Connor教授：虽然淋巴瘤的研究进展可能没有我们期待的那么丰硕，但在CAR-T细胞治疗领域即将出现新的进展。CAR-T细胞疗法主要与B细胞淋巴瘤和多发性骨髓瘤相关；由于改造T淋巴细胞以靶向其恶性T细胞靶标的复杂性，T细胞淋巴瘤中的CAR-T细胞疗法仍然存在重大挑战。
来自伦敦大学学院的团队在针对T细胞受体β链（T细胞淋巴瘤中较不明显的靶标）研究方面取得了重大进展，他们通过创新方案成功开发了可以针对T细胞恶性肿瘤特定靶标的CAR-T细胞疗法。研究的早期数据令人鼓舞，表明免疫治疗药物除了可用于间变性大细胞淋巴瘤外，在治疗其他T细胞淋巴瘤方面也颇具潜力。T细胞淋巴瘤未来的治疗希望与CAR-T细胞技术的持续进步以及新药组合策略息息相关，从而有望进一步改善这种极具挑战性的恶性淋巴瘤的自然病程进展。
Oncology Frontier-Hematology Frontier: What other remarkable research progress has been made in the diagnosis and treatment of lymphoma over the past year? Could you share some insights?
Dr. Owen O'Connor: While progress in lymphoma research may not have been as extensive as we'd hope for, there are intriguing developments on the horizon, particularly in the realm of CAR T-cell therapy. Although CAR T-cell therapy has been primarily associated with B-cell lymphomas and multiple myeloma, it remains a challenge in T-cell lymphomas due to the complexities of engineering T lymphocytes to target their malignant T-cell counterparts.
One promising development comes from the University College London, where a research team has made significant strides in targeting the T-cell receptor beta chain, a less obvious target for T-cell lymphoma. Through innovative research, they have successfully developed CAR T-cells that aim to tackle this specific target on T lymphomas. Early data from their efforts are encouraging, showing some of the most promising results in immunologic drug development for T-cell lymphoma, aside from experiences with drugs like rituximab in anaplastic large cell lymphoma. The future of T-cell lymphoma treatment appears to hinge on the continued evolution of CAR T-cell technology, coupled with innovative combinations of novel drugs, offering hope for transforming the natural history of this challenging blood cancer.
专家简介
Owen O’Connor教授
美国哥伦比亚大学医学中心主席
美国淋巴瘤联盟主席
哥伦比亚大学医学中心Herbert Irving综合癌症中心淋巴发展和恶性肿瘤项目的联合项目主任，淋巴恶性肿瘤中心主任
在管理霍奇金淋巴瘤和非霍奇金淋巴瘤以及开发治疗这些疾病的新药物方面具有国际权威。专注于发现和开发治疗淋巴瘤的新药，到目前为止，已率先开发了三种被批准用于治疗淋巴瘤的新药，并已发表200多篇关于淋巴瘤治疗的文章、书籍章节和评论等。