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李兰芳教授与加州大学旧金山分校（UCSF）医学院庄渭云教授展开中外对话，盘点蕈样肉芽肿（MF）与Sézary综合征（SS）的最新治疗策略。

《肿瘤瞭望-血液时讯》：近年来在治疗蕈样肉芽肿和Sézary综合征方面有哪些最重要的进展，这些进展如何影响了患者的治疗效果？

Oncology Frontier-Hematology Frontier：What are the most significant advances in the treatment of mycosis fungoides and Sézary syndrome in recent years, and how have these impacted patient outcomes?

李兰芳教授：在我国，蕈样肉芽肿与Sézary综合征并不属于高发疾病。由于这两种疾病的早期皮肤表现往往难以准确诊断，导致许多患者到医院就诊时已处于晚期或疾病进展阶段，此时便需要采取更为积极的治疗措施。随着医学研究的不断进步，新药层出不穷，例如组蛋白去乙酰化酶（HDAC）抑制剂西达本胺和CD30单抗等，这些药物已在临床应用中展现出显著疗效。CCR4单克隆抗体，在国外已有较长时间的应用历史，并取得了极佳的治疗效果。尽管该药物在我国已上市，但由于上市时间相对较短，加之价格因素和药物可及性的限制，目前仅有一部分患者能够接受该治疗，尚未能实现广泛应用。值得庆幸的是，随着这些新型治疗药物的不断涌现，我们观察到患者的病情可得到有效控制，无进展生存期（PFS）亦显著延长。

Professor Lanfang Li: In China, mycosis fungoides and Sézary syndrome are not highly prevalent diseases. Due to the difficulty in accurately diagnosing the early skin manifestations of these two diseases, many patients present at hospitals in the advanced or progressive stages of the illness, necessitating more aggressive therapeutic interventions. With continuous advancements in medical research, new drugs have emerged in an endless stream, such as the chidamide and CD30 monoclonal antibody, which have demonstrated remarkable efficacy in clinical applications. The CCR4 monoclonal antibody has a longer history of use in foreign countries and has achieved excellent therapeutic outcomes. Although this drug has been marketed in China, due to its relatively short time on the market, coupled with pricing factors and limitations in drug accessibility, it is currently only accessible to a portion of patients and has not yet achieved widespread application. Fortunately, with the continuous emergence of these novel therapeutic agents, we have observed that patients' conditions can be effectively controlled, and the progression-free survival has also been significantly extended.

庄渭云教授：维布妥昔单抗（Brentuximab）是一种针对CD30的抗体药物偶联物，在蕈样肉芽肿与Sézary综合征的治疗上取得了极大进展，尤其是对过去本会因该病而死亡的晚期疾病患者而言。以往我们只能为患者提供化疗，但他们在很短的时间内都会对化疗产生耐药性。维布妥昔单抗真正填补了存在大量多发性肿瘤病灶、淋巴结受累或内脏受累情况时的治疗空白，并取得了极大成功。可以说，这确实挽救了许多生命。

Professor Weiyun Zhuang: For instance，brentuximab，which is a CD30-directed antibody drug conjugate，has had really great advancement in mycosis fungoides and Sézary syndrome，especially in patients who have advanced stage disease, who would have died from this disease in the past。We would just treat them with chemotherapy，but they all gain resistance to chemotherapy in a very short duration of time. The brentuximab really fill the gap where people have very large multiple tumor lesions or lymph node involvement or visceral involvement and has had a really great success。So that definitely have saved a lot of lives, I would say.The other target therapy is a CCR4-directed antibody treatment called mogamulizumab. It's particularly active in patient with Sézary syndrome or patient with mycosis fungoides，both with a high disease burden in the blood compartment。The medium survival for Sézary syndrome from diagnosis was about 5 years in the past。So I think it's a life-threatening high-risk disease and mogamulizumab really had made impact on those patients. And many patients have complete remission or complete molecular remission In that without treatment and many remissions are quite durable.So I think that's a great success as well in the field。

《肿瘤瞭望-血液时讯》在治疗MF和SS时面临的最大挑战是什么，这些挑战如何影响治疗决策？

李兰芳教授：当前，在我国MF和SS治疗领域中，面临两大亟待攻克的问题。其中，首要问题在于提升淋巴瘤的早期确诊率。淋巴瘤的诊断流程往往需要在具备高度专科化的医院或科室中进行，遗憾的是，众多患者常常在历经多家医疗机构，特别是皮肤科的辗转就诊后，才最终抵达淋巴瘤专科接受专业诊疗，但此时多已步入疾病晚期阶段。针对早期患者，通过采取简单的光疗手段，即可实现病情的有效控制。若能及时对这类预后良好、进展相对缓慢的疾病进行早期干预，患者将能享有更优质的生存状态。因此，如何实现早期诊断无疑成为摆在我们面前的重大挑战。为了应对这一挑战，可以通过系统的专科培训，深化患者对淋巴瘤疾病的认识，同时强化淋巴瘤专科医生及病理医生的早期诊断技能，以确保临床医生能够更早、更迅速地启动治疗，从而有效提升患者的生存率。

Professor Lanfang Li：Currently, in the field of mycosis fungoides and Sézary syndrome treatment in China, we are confronted with two major challenges that require urgent resolution. The foremost challenge lies in improving the early diagnosis rate of lymphomas. The diagnostic process for lymphomas typically necessitates highly specialized hospitals or departments. Regrettably, many patients often undergo a lengthy odyssey through multiple medical institutions, particularly dermatology departments, before finally reaching lymphoma specialty clinics for professional diagnosis and treatment, at which point the disease has often progressed to an advanced stage. For early-stage patients, effective disease control can be achieved through simple phototherapy. Early intervention in such diseases, which have favorable prognoses and relatively slow progression, can enable patients to enjoy better quality of life. Therefore, achieving early diagnosis undoubtedly poses a significant challenge before us. To address this challenge, systematic specialty training can be implemented to deepen patients' understanding of lymphoma diseases, while also enhancing the early diagnostic skills of lymphoma specialists and pathologists, ensuring that clinicians can initiate treatment earlier and more promptly, thereby effectively improving patients' survival rates.The second challenge focuses on the treatment strategies for patients with advanced disease progression. Although MF and SS are categorized as chronic diseases, the treatment difficulty increases significantly when the disease progresses rapidly, prompting some patients to even consider transplantation as a rescue measure. In this context, selecting appropriate targeted therapies and formulating correct treatment plans accurately have become crucial factors determining the success of subsequent treatment. Lymphoma specialists need to rely on their profound professional knowledge and clinical experience to tailor more precise treatment pathways for patients, aiming to achieve optimal disease control.In summary, for patients with MF and SS, timely referral from dermatology to hematology or lymphoma departments for professional assessment and treatment is particularly crucial. Furthermore, strengthening close interdisciplinary collaboration and establishing professional multidisciplinary teams hold immense value in improving the accuracy of early lymphoma diagnosis and the overall treatment effectiveness.

庄渭云教授：蕈样肉芽肿和Sézary综合征治疗中面临的最大挑战在于疗效的持久性。患者虽会产生应答并进入缓解期，但缓解期通常不会持续很长时间，且这两种疾病目前尚无治愈方法。除了移植这一风险较高的选项外，当前的主要挑战在于如何延长PFS或缓解期，以及如何联合多种治疗方法以获得更佳的应答效果。

Professor Weiyun Zhuang：I think the most significant challenges in MF and SS treatment is the longevity of the response。So people would respond，they going to remission。They won't stay in remission for very long and it's not curable disease。So except for probably allogenic transplant， which is obviously very high risk procedure。So I think the Challenge is how are we gonna be able to improve the PFS or the duration of remission？So or maybe how we can combine treatments so give them a better response。I think those are the most challenges。One is get getting a better response because most of the drugs even the very good ones，the response rate is between 30% to 50%. Brentuximab in that advanced stage disease the response rate is 64%. Across the whole stage 1b to four, The response rate is only 37%，but in the advanced stage diseases the 64% response risk is like one of the best。And then the mogamulizumab，even in the most active disease like Sézary syndrome，the response rate is only 37%， like HDAC inhibitors, I wish we have chidamide that's a better choice。But we only have like romidepsin which is infusion and every week is infusion and each time is 4 hours and that's very toxic to us to be honest。But that response rate is only 30%。So there are a lot of room for improvement to improve the response。The other issue is how do we gain a longer response and that we have a better drug that will be fine and but maybe maintenance treatment，it is a strategy，but maintenance treatment requires a drug that's very well tolerated because you can't take anything for like a year if it's very toxic。And just remember this is an incurable condition。So when people gonna need treatment for their lifetime， a transplant is very high risk。I still think that transplant works the best in SS and doesn't work as well in MF。But there's a donor availability，there's a social support that go through the process is a very big deal。The toxicity is it's still but 10% of mortality just from just from the treatment itself。

《肿瘤瞭望-血液时讯》在您们的治疗实践中，如何考虑蕈样肉芽肿和Sézary综合征的治疗策略，您们在各自地区发现了哪些独特的有效方法？

Oncology Frontier-Hematology Frontier：In your treatment practices, how do you consider the therapeutic strategies for mycosis fungoides and Sézary syndrome, and what unique effective approaches have you discovered in your respective regions?

Professor Lanfang Li：When discussing the optimal treatment strategies for these two diseases, it is crucial to acknowledge that the newest treatment does not necessarily equate to the best. In fact, selecting the best treatment strategy necessitates a comprehensive consideration of the patient's different stages and disease states. For some early-stage patients, traditional therapies such as phototherapy and radiotherapy have already provided excellent long-term control. For those patients who were previously in the progressive stage, the advent of more novel drugs now enables them to achieve optimal disease control as well.Therefore, for mycosis fungoides and Sézary syndrome, specialists need to devise the most suitable treatment plan based on the specific condition of each patient. Additionally, China boasts some unique medications, such as chidamide, which was previously mentioned. In the United States, this drug is typically administered intravenously, but our oral formulation offers greater convenience to patients, especially for those who need to take it at home, making it a superior option. Furthermore, with the continuous emergence of new drugs, patients with advanced diseases have benefited greatly, with significant improvements in disease control. These new drugs not only bring new therapeutic hope to patients but also further enrich our treatment options.

庄渭云教授：传统上，治疗策略的选择主要依据疾病的分期。这一方法至今仍然被视为有效，并在日常医疗实践中广泛应用。然而，对于近期开发的新型药物，如维布妥昔单抗或CCR4抗体等，它们展现出独特的生物学特性，且更为重要的是，在不同疾病部位的临床活性存在显著差异。具体而言，布伦妥昔单抗在治疗肿瘤病灶方面展现出了显著疗效，但在处理血液受累的情况时则效果有限。相反，CCR4抗体在治疗血液受累方面表现出色，然而，在存在肿瘤病灶或淋巴结受累的情况下，其疗效则大打折扣。鉴于此，基于这些新型药物在不同疾病部位的临床活性差异，需要精确评估患者体内疾病负担最重的部位，并据此来制定治疗策略。这一理念体现了靶向治疗和多种生物制剂的独特性，与我们所熟知的化疗药物相比，存在显著区别。因此，这可以被视为一种新兴的治疗策略，且已在日常医疗实践中得到广泛应用。这一策略的重要性不言而喻。

Professor Weiyun Zhuang：Conventionally，we have been choosing the treatment strategies based on stage。I think that's still a very valid approach and we still do it on a daily basis。But for the most recent developed new drugs like brentuximab or CCR4 antibody and some others，they have very unique biological features，but more importantly，they have different clinical activities in different compartments of diseases，for instance，like brentuximab is particularly good for tumor lesions or lymph nodes are not so great for the blood involvement。And CCR4 anybody is fantastic for blood involvement，but not good at all if you have tumor lesions or lymph node involvement。So based on their different clinical activities in different disease compartment， what kind of compartment has the heavy largest disease burden in the patients？We like to choose the treatment strategy based on that。So I think that's unique for target therapy and unique for many biologic。And that's different from the chemo agents that we use in we're more familiar with。So I think that's a recently developed strategy。We used that on a daily basis。I think that's very important。

专家简介

李兰芳 教授

肿瘤学博士

天津市肿瘤医院淋巴瘤科副主任医师

中国抗癌协会淋巴瘤专业委员会委员

天津市抗癌协会淋巴瘤专业委员会常

委天津市抗癌协会肿瘤临床化疗专业委员会常委

2008年赴美国内布拉斯加大学医学中心进修

2014年赴美国莫菲特癌症中心访问学习

在国内外期刊发表论文数篇承担及参与多项国家级课题

专家简介

庄渭云 教授

加州大学旧金山分校（UCSF）医学院血液学和肿瘤学临床副教授

加州大学旧金山分校多学科皮肤淋巴瘤诊所共同主任

庄渭云教授在美国哥伦比亚大学医学院获Ph.D，后在美国斯坦福大学医学院获M.D.，同时在UCSF内科完成住院医师培训和临床fellow。庄教授的研究主要集中在皮肤T和NK/T细胞淋巴瘤以及EBV相关的弥漫性大B细胞淋巴瘤，并在国际相关领域获得多项奖项，包括美国临床肿瘤学会（ASCO）、淋巴瘤研究基金会、美国癌症研究协会（AACR）、美国血液学会（ASH）奖。庄教授同时担任美国ASCO学会委员、美国ASH学会委员、美国AACR协会委员、国际皮肤淋巴瘤学会委员和美国皮肤淋巴瘤联盟委员。