为了进一步提升我国白血病与淋巴瘤的诊疗技术水平，由中国临床肿瘤学会（CSCO）、CSCO白血病专家委员会以及淋巴瘤专家委员会联合主办，哈尔滨血液病肿瘤研究所与北京大学肿瘤医院共同承办的“CSCO第八届血液肿瘤学术大会”，于7月26日至28日在哈尔滨盛大举行。此次大会旨在为众多血液肿瘤学领域的专家学者们搭建一个深入学习与广泛交流的重要平台。在大会召开之际，《肿瘤瞭望-血液时讯》特别邀请美国淋巴瘤联盟主席/弗吉尼亚大学癌症中心Owen O’Connor教授，围绕外周T细胞淋巴瘤（PTCL）的前沿进展，进行了深入的学术探讨与精彩分享。

《肿瘤瞭望-血液时讯》您认为目前治疗PTCL面临的最大挑战是什么？您在今天的演讲中提到了PTCL的最新进展，能否具体谈谈今年在这一领域取得了哪些关键性突破？

Owen O’Connor教授：在PTCL的研究与治疗领域，我们正面临着一系列复杂且严峻的挑战。首先，PTCL在美国的发病率相对较低，年发病例数仅约为一万至一万五千例，这使得其在临床研究和治疗策略的制定上显得尤为困难。然而，更为关键的是，目前已识别出数种不同的T细胞淋巴瘤亚型，这些亚型展现出了令人惊叹的异质性和高度多样性。上述两项挑战不仅增加了诊断的复杂性，也使得制定统一的治疗策略变得极为困难，特别是对于一线和复发患者，这构成了我们在疾病管理中面临的第三项重大挑战。

目前，PTCL的治疗主要依赖于传统的化疗方案，这些方案往往基于历史数据和经验积累。尽管如此，随着医学研究的不断深入，新兴的治疗手段，如靶向治疗和免疫治疗，正在逐步进入临床实践，展现出广阔的应用前景。这些新兴疗法的开发和应用，为我们提供了更多治疗PTCL的可能性，但同时也带来了新的挑战，即如何在众多亚型中找到最有效的治疗方案。

另一大类挑战则聚焦于生物学层面。相较于其他癌症类型，T细胞淋巴瘤在生物学研究方面进展较缓慢，但在过去二十年中，病理学家和分子生物学家们已取得了显著成就。他们成功定义了多种不同的T细胞淋巴瘤亚型，并揭示了这些亚型独特的分子特征图谱。这些发现不仅加深了我们对PTCL生物学特性的理解，也为针对性治疗药物的开发提供了重要的生物学基础。

然而，如何确定并优化具有针对性的治疗药物成为另一项难题。为了推动新型治疗的科学发展，科学家们亟需高质量的实验室模型，包括细胞系和小鼠模型，并需掌握相应的实验技术。这些模型不仅能够帮助我们更好地理解T细胞淋巴瘤的生物学机制，还能够在药物筛选和疗效评估中发挥关键作用。因此，若能采用科学的策略优化治疗，并聚焦于亚型中普遍存在的关键生物学机制，实施精准治疗，我们有望在治疗领域取得显著的突破与进展。

Oncology Frontier-Hematology Frontier：What do you consider to be the greatest challenges in the treatment of Peripheral T-cell Lymphomas (PTCL) at present? In your presentation today, you mentioned the latest advancements in PTCL. Could you elaborate on what key breakthroughs have been achieved in this field this year?

Dr. Owen O’Connor：There are so many challenges. It's gonna be hard to summarize them all in a short period of time. The two biggest and obvious challenges are that these are incredibly rare diseases in the United States, only about 10,000 to 15,000 cases per year. These are incredibly heterogeneous diseases, very diverse. We now recognize nearly 36 kinds of T cell lymphoma. Those two challenges make it very hard to develop a consensus around how best to manage these diseases.

In fact, the lack of a consensus on care be it in frontline or relapse setting is probably the third big Challenge. We have regimens that are predicated on combination chemotherapy developed in the past. They have been, by default, become the new standards of care. But those three aspects conspire to create enormous Challenge.

The next big category of challenges revolves around biology. Many cancers have clear biological underpinnings, and we can point to targets. The networks in T cell lymphoma that has been slow to evolve. Pathologists have done a great job over the last 20 years, really defining the different sub types, defining their unique molecular profiles. And that coupled with some new drugs. And the Information from those new drugs has informed us that maybe there is a biological basis for these diseases. And that biological basis, maybe its underlying dis-regulated, epigenetic biology. One of the great challenges then cut that comes from that is what are the drugs we have available to target that biology? Are those drugs optimized? And in my opinion, from the former colleges perspective, they're not optimized. From the point of view of how do we understand the scientific basis for how to move those drugs forward? Scientists need good laboratory models. They need cell lines, they need mouse models, and they need know how. And that represents a really huge Challenge, because most of the advances we try to make in the disease are based upon random selection of drugs, not science, the science is retrofitted.

So I think if we can find a way to think about how to survey these drugs that try to target the critical underlying biology that's common across the 36 sub types will be able to make progress. And in my opinion, that progress will be made by developing new chemotherapy, Free platforms predicated on those targeted therapy combinations.

《肿瘤瞭望-血液时讯》在您的研究和实践中，您认为目前治疗PTCL最有效的策略是什么？您如何评价新的治疗手段，比如免疫疗法或靶向疗法在PTCL治疗中的潜力？

Owen O’Connor教授：在过去的三十至四十年间，尽管我们不懈努力，但PTCL的治疗进展相对有限。目前，基于CHOP的化疗方案仍被视为标准治疗手段，并在全球多地广泛应用于患者。在患者达到首次缓解时，自体造血干细胞移植通常被视为一种普遍的治疗选择。在确立更优治疗标准之前，我们推荐患者在一线或复发状态下积极参与临床试验。事实上，无论是NCCN指南，还是北美洲、欧洲乃至亚洲的权威指南，均建议患者在治疗初期即考虑加入临床试验。值得注意的是，并非每位患者都能参与临床试验，但通过跨国界、跨地区的广泛合作，我们能够促使更多患者从最新的治疗进展中获益。

此外，免疫治疗作为一个充满潜力的领域，正吸引着全球科研团队的关注。尽管免疫检查点抑制剂和CAR-T疗法在PTCL治疗中的应用尚需时日来完善和发展，但世界各地科研团队所取得的诸多显著进展和积极成果，预示着这些治疗方法有望为患者带来实质性的临床获益。

Oncology Frontier-Hematology Frontier：In your research and practice, what do you believe to be the most effective strategies for treating PTCL currently? How do you assess the potential of new therapeutic approaches, such as immunotherapy or targeted therapy, in the treatment of PTCL?

Dr. Owen O’Connor：Unfortunately, we haven't made many advances over the last 30 or 40 years, chop based chemotherapy or widely regarded as standard, and in many parts of the world for the appropriate patient. Those patients go on to receive an autologous stem cell transplant in first remission. That's probably the universal standard in some form. I believe that in my practice, we use clinical trials, not everybody has access to clinical trials. So that becomes harder, but where we can collaborate in a country or in a region or a city with colleagues that do have clinical trials for these diseases. I believe a clinical trial in the front line and the relapse setting should be the standard of care until we define better standards of care.In fact, if you look at the NCCN criteria, or the criteria from North America, Europe, even Asia, recommend clinical trials very early in the care of patients.

Regarding immunotherapy, I think it's a fascinating area. It's taken us a long time. Immune checkpoint inhibitors are not terribly active by themselves. CAR-T is taking a long time to develop in these diseases. But I think there are lots of interesting advances and developments by various groups around the world. That suggests that those kinds of treatments will soon become available with meaningful clinical benefit for all patients.

《肿瘤瞭望-血液时讯》您在演讲中提及了新希望，那么对于PTCL治疗领域来说，患者如何能够拥抱这份新希望呢？广大学者和临床人员又该如何更有效地为更多患者带来新希望呢？展望未来，您认为具有“新希望”的PTCL治疗的发展方向会是怎样的？

我认为，新的希望之光唯有通过医疗部门与政府的紧密合作方能绽放。单打独斗无法达到我们的目标，唯有携手并进，以团队之力方能攻坚克难。此外，我们还需要进行深入的探索与研究，以明确哪些生物学靶点具备潜在的靶向治疗价值，并随后将这些新兴疗法与当前的标准治疗进行科学且系统的对比。在临床试验和真实世界中实施这些策略，不仅切实可行，更是我们取得突破性进展的必由之路。

Oncology Frontier-Hematology Frontier：You mentioned 'new hope' in your speech. How can patients in the field of PTCL treatment embrace this new hope? How can scholars and clinicians more effectively bring new hope to more patients? Looking forward to the future, what do you think is the development direction of PTCL treatment with "new hope"?

Dr. Owen O’Connor：New hope is tied to the last , and the new hope has to be based on research. The key, whether you're a patient, a government, physicians, foundations, is to make sure that we allocate dollars for that research. There are very few doctors around the world that do research in these diseases. Lots of doctors treat a lot of doctors will put together clinical trials, but fundamental research on how to exploit the biology, to find new therapies that's rare.

And I think the new hope has to be that form of the private sector, the government and physicians with interests, including those institutions where the physicians work is going to become very important to coalesce a singular community. Working individually is not going to do it. We're gonna have to work as a team. But I think for me, trying to figure out what's the biology worth targeting is important, and then comparing those new therapies against our standard of care. In randomized studies, in the clinic, which isn't hard and can be done, is gonna be the only way we make those advances.

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