第五届天津国际淋巴瘤学术会议作为促进国际学术交流与合作的学术平台，积极发挥了其桥梁作用，促进了国际淋巴瘤领域的深入交流与合作。会议期间，《肿瘤瞭望-血液时讯》特邀天津医科大学肿瘤医院邱立华教授与美国德克萨斯大学MD安德森癌症中心Swaminathan Iyer教授展开中外对话，盘点外周T细胞淋巴瘤（PTCL）的最新治疗进展以及治疗策略的优化方向。

 

 

Oncology Frontier-Hematology Frontier：In light of the recent breakthroughs in PTCL treatment，what are your thoughts on the evolution of therapeutic strategies，and how do these advancements compare between China and your regions?and what considerations should be taken into account when updating treatment protocols between different healthcare systems?

Swaminathan Iyer教授：T细胞淋巴瘤是一种相对罕见的恶性肿瘤，在美国尤其如此，该疾病包含多种亚型，其特征在于高度的侵袭性。目前，其尚无公认的标准治疗方案，且具有较高的复发率。因此，在治疗和管理方面存在诸多挑战。我同样观察到美国与中国在T细胞淋巴瘤的流行病学上存在显著差异，中国的T细胞淋巴瘤患者较多，尤其是NKTCL。

 

在当今全球化的世界中，我们共同构成了一个医学研究共同体，相互之间的学习和交流显得尤为重要。近年来，中国已在开发针对T细胞淋巴瘤的治疗方法方面取得了显著进展，包括众多新型治疗策略。现如今，许多领域的突破性进展源自中国，美国的一些生物技术公司在面对领域挑战时，会越来越多地参考和采纳来自中国的创新成果。这一成就得益于中国庞大的患者群体和研究者队伍，以及生物技术领域的快速发展。实际上，美国的多家公司已经在T细胞淋巴瘤研究领域与中国建立了合作关系，涉及PI3Kδ抑制剂和JAK抑制剂等多种药物的研发。因此，我认为在T细胞淋巴瘤的治疗领域，美国与中国之间的合作是一条双向通道。

 

Professor Swaminathan Iyer:I think it’s a very important question because T cell lymphoma are rare，at least in the US and there are multiple types and they are very aggressive.There’s no standard therapies and they relapse.So there are many challenges.And one of the big differences that we see between the united states and china is that you see a lot more T-cell Lymphoma，particularly the NK/T-cell lymphoma in certain parts of china more than the others.

 

So the world is as one small place and I believe that we have to learn from each other.China has spearheaded many therapies，many chemotherapy agents，novel therapies，because of the numbers and because of the biotechnology sector.We，in fact，are doing many studies in the us in collaboration with many companies in china，whether it is the novel，PI3Kδinhibitor，or whether it is the JAK inhibitor.So I think it’s a two way street between the us and china.The numbers are smaller in the us and there are many biotech companies，but I think it’s a lot of these innovations are coming from china.

邱立华教授：外周T细胞淋巴瘤（PTCL）在中国较为常见，其治疗难度较大。近二十年来，国内、外学者做了大量探索性工作以期提高疗效并改善生存。令人鼓舞的是该领域已取得了可喜的进展。首先，我们推荐条件合适的患者，在首次治疗达到完全缓解时，即接受自体造血干细胞移植，数据显示对改善预后有益。

 

另一方面，中国研发的新药不断涌现，为PTCL的治疗开辟了新途径。十余年前，国际上研发出表观遗传学药物，特别是组蛋白去乙酰化酶（HDAC）抑制剂，在小分子靶向药物领域展现出20%～30%的客观有效率。在此基础上，近年来，新药研发日新月异，客观疗效更是达到新高度，这些药物包括PI3K抑制剂（如林普利塞）、EZH2抑制剂（如他泽司他），以及JAK1抑制剂（如戈利昔替尼）等，这几类药物均展现出了卓越的疗效，将治疗有效率提升至40%～50%的较高水平，为PTCL患者带来了新的希望。

 

具体到我国特有的病种，PTCL中的最常见类型：NK/T细胞淋巴瘤（NKTCL），具有鲜明的中国特色，其治疗策略与欧美国家常见的PTCL类型迥异。在欧美国家PTCL常见类型的标准治疗中，CHOP联合其新药（CHOP+X）已成为为基石性方案，在除NK/T以外的其他PTCL类型治疗中被广泛应用。然而，对于NKTCL而言，培门冬酰胺酶为其基石性治疗药物，如P-GemOx方案等均包含该药，这些方案在临床实践中取得了令人瞩目的疗效，体现了我国在该领域治疗策略的独特性、开创性、有效性和贡献性。

 

Professor Lihua Qiu：Peripheral T-cell lymphoma(PTCL)is relatively common in China，posing significant challenges in treatment.Over the past two decades，domestic and international scholars have conducted extensive exploratory work aimed at enhancing therapeutic efficacy and improving survival outcomes.Encouragingly，remarkable progress has been made in this field.Firstly，we recommend that eligible patients undergo autologous hematopoietic stem cell transplantation upon achieving complete remission after initial treatment，as data indicate its beneficial effects on prognosis.

 

On the other hand，the continuous emergence of novel drugs developed in China has opened up new avenues for PTCL treatment.Over a decade ago，epigenetic drugs，particularly histone deacetylase inhibitors，were developed internationally，demonstrating an objective response rate of 20%to 30%in the realm of small-molecule targeted therapies.Building upon this foundation，recent years have witnessed rapid advancements in new drug development，with objective efficacy reaching new heights.These drugs include PI3K inhibitors(such as linperlisib)，EZH2 inhibitors(like tazemetostat)，and JAK1 inhibitors(like golidocitinib)，all of which have demonstrated exceptional efficacy，elevating the treatment response rate to a higher level of 40%to 50%，bringing renewed hope to PTCL patients.

 

Specifically，regarding the unique disease entity prevalent in China，the most common subtype of PTCL—NK/T-cell lymphoma—exhibits distinct Chinese characteristics，necessitating a treatment strategy vastly different from that for common PTCL types in Europe and the United States.In the standard treatment of common PTCL types in Western countries，CHOP combined with novel agents，CHOP+X，has become the cornerstone regimen，widely applied in the treatment of PTCL subtypes other than NK/TCL.However，for NKTCL，pegaspargase serves as the cornerstone therapeutic agent，with regimens such as P-GemOx incorporating this drug，achieving remarkable clinical efficacy.These achievements underscore the uniqueness，innovation，effectiveness，and contribution of China’s treatment strategies in this field.

 

 

Oncology Frontier-Hematology Frontier：What are the current challenges in PTCL treatment that need to be addressed，and how do you see the role of collaborative research in overcoming these hurdles?

Swaminathan Iyer教授：在T细胞淋巴瘤的研究与治疗领域内，我们面临着诸多复杂且多维度的挑战。首要挑战聚焦于诊断的精确性与全面性。值得注意的是，T细胞淋巴瘤并非单一疾病，而依据最新的世界卫生组织（WHO）及国际共识分类（ICC）标准，细分为至少32种亚型，且尚有诸多边缘病例难以明确归类，这要求我们未来的研究需致力于构建更为完善的分类体系。T细胞淋巴瘤的诊断流程起始于形态学评估，进而结合免疫表型及分子分型分析，虽这一综合方法在一定程度上提升了诊断的准确性，但仍对病理学家提出了高要求，他们需深度融合丰富的临床信息与显微镜下观察到的细微差异，以实现精准诊断。

 

其次，治疗策略的制定同样充满挑战。我们虽从B细胞淋巴瘤的治疗中汲取了诸多经验，如CHOP方案作为标准治疗之一，但其适用性有限，仅对部分患者奏效。因此，探索并采用了如DDGP等替代方案。然而，鉴于多数T细胞淋巴瘤患者在确诊时已处于晚期，伴随高国际预后指数（IPI），这显著增加了治疗难度，常需辅以自体或异基因干细胞移植以巩固疗效。

 

再者，EBV的感染状态构成了另一重大挑战。EBV不仅能够影响淋巴细胞系（包括T细胞与B细胞）的生物学特性，还可能引发一系列并发症，如噬血细胞综合征（HLH），进一步加剧了疾病管理的复杂性。

 

最后，从治疗资源的角度来看，目前针对T细胞淋巴瘤的获批疗法相对有限，特别是在美国，目前主要治疗选择仅有三种，这对于复发或难治性患者而言显然不足。因此，拓宽治疗选择，加强临床研究，以探索更多有效疗法显得尤为迫切。

 

鉴于上述挑战，加强国际合作与知识共享显得尤为重要。中国作为全球T细胞淋巴瘤患者数量众多的国家之一，其研究资源与价值不可忽视。作为T细胞淋巴瘤诊断与治疗领域的先行者，MD安德森癌症中心深信，通过与中国各大医学中心的紧密合作，能够共同推动该领域的发展。我们已着手与中方伙伴探讨建立合作性回顾性数据库的可能性，旨在整合病理学、分子分型及临床研究成果，为未来的治疗方案优化提供坚实的数据支持。尽管前路漫长，但此次合作无疑是一个充满希望的起点，预示着我们在T细胞淋巴瘤领域将取得更多突破性进展。

 

Professor Swaminathan Iyer:I think T-cell Lymphoma are many challenges.The first one is the number of diagnosis.It’s not one disease.According to the recent WHO and ICC there are at least 32 different entities.There are many others that don’t quite fit the description.So we try and push them towards one of these areas.The initial diagnostic pathways are based on morphology followed by immunophenotype and molecular studies.Broadly this more morphological immunophenotype approach has helped us with the diagnosis but they still remain a challenge for the pathologist because they need a lot of clinical information t o put the context to what they see in the microscope.

 

The second is therapies.We have borrowed a lot of therapies from B cell lymphoma.As professors mentioned，a CHOP as a standard of care，but it may not work for everybody there.So we use something like DDGP regimens.And even these where they work very well in early stages，many of the T cell lymphomas have advanced stages，high international prognostic index that puts us in a challenge that we have to consolidate them with an autologous stem cell transplantation or an allogeneic transplantation.

 

The third problem is that many of these lymphomas are have EBV and EBV becomes a challenge and EBV causes problems，not only because it transforms the lymphoid cell lines，whether it’s T cells or B cells and it can bring other issues such as hemophagocytic lymphohistiocytosis.

 

And finally I think there are not many therapies.If you look at the United States approval，there are three major approvals product.Is since most of these patients relapse having three options is not enough.So we need a more therapeutics，more clinical studies.So that’s where I think the collaborations and the learning from each other helps because china sees so many peripheral lymphoma and we at MD Anderson are the forefront of some of these diagnostic and therapeutic modalities for T cell lymphoma.I think it’s very natural that we work together in this particular area and come up with solutions.And we have had discussions with various groups here in china to try and come up with a simple，collaborative retrospective databases，including pathology reviews，molecular pathways and also in clinical studies.

 

So I think there’s long ways to go，but I think it might be a good start for us to have this collaboration，particularly in peripheral lymphoma.

邱立华教授：当前，对PTCL患者的治疗优先推荐参加临床试验。鉴于PTCL的高度异质性，未来的研究方向应聚焦于改善预后，其中首要的是针对不同病理亚型的精细优化治疗策略。这一策略的核心在于：针对每一具体病理亚型实施“分而治之”的个性化治疗方案。

 

为了深化对病理类型的理解，须深入开展科学研究，尤其是在基因层面。这要求我们在基础研究上投入大量精力，致力于筛选并鉴定出那些具有关键调控作用或类似限速酶作用的靶基因。基于这些发现，进而致力于新型药物的研发，并严谨评估其疗效，以期实现治疗上的重大突破。

 

值得注意的是，由于PTCL在欧美国家的发病率相对较低，而在中国则更为常见，这凸显了国际多中心合作的重要性。通过跨国界的合作，我们能够更有效地验证新型药物的治疗效果，共享研究成果，从而加速治疗进展，最终惠及全球患者。这种合作模式不仅有助于提升整体治疗水平，也是实现医学进步的重要途径。

 

Professor Lihua Qiu：Currently，participation in clinical trials is the preferred recommendation for the treatment of PTCL patients.Given the high degree of heterogeneity in PTCL，future research directions should focus on improving prognosis，with a primary emphasis on refined and optimized treatment strategies tailored to different pathological subtypes.The cornerstone of this strategy lies in implementing personalized"divide and conquer"therapeutic approaches for each specific pathological subtype.

 

To deepen our understanding of pathological types，extensive scientific research，particularly at the genomic level，is imperative.This necessitates significant investment in basic research to screen and identify target genes that play pivotal regulatory roles or function akin to rate-limiting enzymes.Based on these discoveries，efforts should be directed towards the development of novel drugs，with rigorous evaluations of their efficacy，aiming to achieve significant breakthroughs in treatment.

 

It is noteworthy that the relatively low incidence of PTCL in European and American countries compared to its higher prevalence in China underscores the importance of international multi-center collaboration.Through cross-border cooperation，we can more effectively validate the therapeutic effects of novel drugs，share research outcomes，and thereby accelerate treatment advancements，ultimately benefiting patients worldwide.This collaborative model not only contributes to enhancing the overall level of treatment but also serves as a vital pathway towards medical progress.

 

 

Oncology Frontier-Hematology Frontier：How do you envision the future of PTCL treatment，especially with the advent of novel agents and precision medicine approaches?

 

Swaminathan Iyer教授：我们正站在一个领域的转折点上，见证着基于多元路径的新型疗法的涌现。首先，值得强调的是，在T细胞淋巴瘤各亚型的生物学理解方面，我们已取得了诸多突破性进展与发现。具体而言，PTCL已不再局限于传统的单一治疗框架，而是细化为不同的策略，使得能够精准地基于亚型进行分析和诊治。分子分型方面，依托下一代测序技术的革新，我们不仅能够精准识别突变，更能洞察关键信号通路的异常情况，为我们深入理解其生物学机制提供了可能。

 

在治疗领域，我们已研发出多种新型药物，包括PI3K抑制剂和JAK1/2抑制剂等，这些创新疗法目前正处于积极的临床研究阶段。从过年在美国血液学会年会（ASH）及今年欧洲血液学协会年会（EHA）上公布的数据来看，这些新药展现了令人鼓舞的反应率与持久的完全缓解率，为患者带来了前所未有的希望。此外，在难治复发性的治疗探索中，针对CD94的靶向疗法展现出了潜在的治疗价值，其相关数据预计将于今年ASH会议上揭晓。

 

另一值得关注的重点是噬血细胞综合征（HLH）的治疗进展，无论其诱因是EBV还是微环境异常，新型抑制剂的出现为患者带来了新的治疗选择。EHA年会上的最新摘要显示，新型抑制剂在特定患者群体中展现了良好的治疗效果。

 

至于CAR-T细胞疗法在T细胞淋巴瘤治疗中的应用，尽管起步较晚且面临诸多挑战，但总体上并未落后太多。目前，多个研究团队正积极探索包括CD70、CD5及CD7在内的多样化靶点，力求实现CAR-T疗法的精准化与高效化。同时，单抗与双抗等新型治疗手段也在不断取得进展，预示着未来一两年内，我们将从正在进行的临床研究中获得更为成熟的数据，并自信地宣称，T细胞淋巴瘤的治疗手段将迈入一个全新的、更加优化的时代。

 

Professor Swaminathan Iyer：We are at the inflection，for molecular therapies based on various targets that has been discovered.First thing I want to say is that a lot of advances in understanding of the biology of the various sub-type of T cell lymphoma are ongoing and several discoveries have been made.For example，the PTCL will not otherwise specified is not just a basket of diagnosis.That’s actually three different diagnosis.And today we can sub-type them easily.One of the first themes I would say is sub typing.And the second is molecular analysis.Using Next-Generation Sequencing，we are able to find not just mutations，but also up regulated pathways in these T cell lymphomas.Why？Because it gives us insights into the biology.In the battle section，we’ve had developments of various novel agents，whether it’s PI3K inhibitors or JAK1/2 inhibitors.

 

Several of these agents are now in clinical studies.Phase two have been completed.Recent presentations at ASH from last year and from EHA this year have shown that they have remarkable responses and durable complete remissions.So that gives hope.Now there are also newer therapies in the realm of the T cell lymphoma.And now there is a target unifying target directed against CD94，which seems to be helpful and will have data on ASH this year.The third point is HLH which ii mentioned earlier，either due to EBV or due to the micro-environment and now there is a target therapeutic.In the EHA，we had a late breaking abstract which has shown to benefit these patients.

 

Finally，I think we are not very behind in terms of CAR-T development，even though we started a little late and there were challenges for developing CAR-T，for T-cell lymphoma，the various targets that investigating CD 70 is an active investigation at MD Anderson.We’ve done aloe CD 70 and NK CD70.CD5 is another target.Various groups are doing CD5 CAR-T.CD7 is another target for T-cell lymphoma.So I think we are making progress with normal therapeutics with monoclonal antibodies bispecific monoclonal antibodies and also CAR-T.And I think clearly the clinic on the ongoing studies a in a year or two from now，I think you’ll hear more mature data and will be confident to say that we have better therapies for T-cell lymphoma.

 

邱立华教授：在PTCL的治疗领域，近年来已取得了显著进展。具体而言，对于一线治疗达到完全缓解（CR1）的患者，自体造血干细胞移植巩固已成为重要治疗手段。而对于复发难治的病例，异基因造血干细胞移植则作为目前唯一确切有效的治疗策略被广泛认可。

 

从亚型分类来看，国际视野下，间变大细胞淋巴瘤（ALCL）作为首个重要亚型，其治疗格局因维布妥昔单抗（BV）的引入而发生了根本性变化，不仅更新了治疗指南，还极大地提升了治疗效果，展现出极为广阔的治疗前景。在中国，针对NKTCL的PGemOx等方案的应用为众多患者带来了治愈的希望。此外，血管免疫母细胞性T细胞淋巴瘤（AITL）的治疗亦取得了突破性进展。众多新药的问世，如化疗药物中的米托蒽醌脂质体，以及分子靶向药物中的PI3K抑制剂、JAK1抑制剂和EZH2抑制剂等，均显著提升了治疗效果，单药有效率高达40%至50%，这一成就标志着治疗上的巨大进步。相比之下，外周T细胞淋巴瘤非特指型（PTCL-NOS）的治疗进展虽不如前两者显著，但仍处于不断探索与前进之中。

 

回顾治疗历史，从传统的CHOP方案到如今CHOP+X的联合疗法，尤其是近十年来，表观遗传学药物如HDAC抑制剂（包括罗米地辛、普拉曲沙等）以及国内自主研发的西达苯胺等药物的加入，进一步提升了治疗效果，使疗效提升幅度达到约20%至30%。

 

展望未来，随着科学技术的持续进步，新的作用机制揭示与药物不断涌现，为外周T细胞淋巴瘤的治疗带来了无限可能。我们坚信，“道阻且长，行则将至，行而不辍，未来可期”，这句话激励我们不断探索，为全球患者带来更有效的治疗方法。

 

Professor Lihua Qiu：In the realm of PTCL treatment，remarkable progress have been achieved in recent years.Specifically，for patients achieving CR1 after first-line therapy，autologous hematopoietic stem cell transplantation consolidation has emerged as a crucial therapeutic modality.For recurrent and refractory cases，allogeneic hematopoietic stem cell transplantation is widely recognized as the only definitive and effective treatment strategy currently available.

 

From a subtype perspective，internationally，anaplastic large cell lymphoma stands as the first significant subtype whose treatment landscape has undergone a fundamental transformation with the introduction of brentuximab vedotin.This not only updated treatment guidelines but also significantly enhanced treatment outcomes，presenting an extremely promising therapeutic outlook.In China，the application of regimens such as PGemOx for NKTCL has brought hope of cure to numerous patients.Additionally，breakthroughs have been made in the treatment of angioimmunoblastic T-cell lymphoma.The advent of numerous novel drugs，including Mitoxantrone Hydrochloride Liposome among chemotherapeutics and PI3K inhibitors，JAK1 inhibitors，and EZH2 inhibitors among molecular targeted therapies，has significantly improved treatment efficacy，with single-agent response rates reaching as high as 40%to 50%.This achievement marks a significant step forward in treatment.In contrast，while advancements in the treatment of peripheral T-cell lymphoma not otherwise specified，have been less pronounced than those for the aforementioned subtypes，research and development continue unabated.

 

Looking back at the history of treatment，from the traditional CHOP regimen to the current CHOP+X combination therapies，and particularly over the past decade，the incorporation of epigenetic drugs such as HDAC inhibitors(including romidepsin，pralatrexate，and domestically developed chidamide)has further enhanced treatment outcomes，resulting in an improvement of approximately 20%to 30%in efficacy.

 

Looking ahead，with the continuous advancement of science and technology，the revelation of new mechanisms of action and the continuous emergence of new drugs，have brought unlimited possibilities for the treatment of peripheral T-cell lymphoma.We firmly believe that the saying，"The road ahead is long and arduous，but with perseverance，we will reach our destination.Keep moving forward，and the future is full of promise"inspires us to continue exploring and bring more effective treatments to patients worldwide.