The 5th Tianjin International Lymphoma Academic Conference, serving as an academic platform to foster international academic exchange and cooperation, has actively played its role as a bridge, facilitating in-depth exchange and collaboration in the field of international lymphoma. During the conference, "Hematology Frontier" specially invited Dr. Lanfang Li from the Tianjin Medical University Cancer Institute and Hospital and Dr. Weiyun Zhuang from the University of California, San Francisco (UCSF) School of Medicine, to engage in a China-International dialogue, reviewing the latest treatment strategies for mycosis fungoides (MF) and Sézary syndrome (SS).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?
Dr. 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.
Dr. 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.
Hematology Frontier：What are the most significant challenges you both face in treating MF and SS, and how do these challenges shape your therapeutic decisions?
Dr. 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.
Dr. 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.
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?
Dr. 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.
Dr. 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.
Dr. Lanfang Li
Doctor of Oncology
Deputy Chief Physician, Department of Lymphoma, Tianjin Cancer Hospital
Committee Member of the Lymphoma Professional Committee, Chinese Anti-Cancer Association Standing Committee Member of the Lymphoma Professional Committee, Tianjin Anti-Cancer Association
Standing Committee Member of the Clinical Chemotherapy Professional Committee, Tianjin Anti-Cancer Association
Studied at the University of Nebraska Medical Center in 2008
Visited Moffitt Cancer Center for learning in 2014
Published several papers in domestic and international journals
Undertaken and participated in multiple national-level research projects
Dr. Weiyun Zhuang
Clinical Associate Professor of Hematology and Oncology, University of California, San Francisco (UCSF) School of Medicine
Co-Director of the Multidisciplinary Cutaneous Lymphoma Clinic at UCSF
Professor Zhuang Weiyun obtained her Ph. D. from Columbia University College of Physicians and Surgeons, then her M. D. from Stanford University School of Medicine, and completed her residency training and clinical fellowship in internal medicine at UCSF. Professor Zhuang’s research focuses on cutaneous T-cell and NK/T-cell lymphomas, as well as EBV-associated diffuse large B-cell lymphoma. She has received multiple awards in the international field, including from the American Society of Clinical Oncology (ASCO), Lymphoma Research Foundation, American Association for Cancer Research (AACR), and American Society of Hematology (ASH). Professor Zhuang also serves as a member of the ASCO, ASH, AACR, International Society for Cutaneous Lymphomas, and the Cutaneous Lymphoma Alliance.
