Editor's Note: To further enhance the diagnosis and treatment of leukemia and lymphoma in China, the 8th Hematology Academic Conference, jointly organized by the Chinese Society of Clinical Oncology (CSCO), CSCO Leukemia Expert Committee, and CSCO Lymphoma Expert Committee, and co-hosted by Harbin Institute of Hematology and Oncology and Peking University Cancer Hospital, was held grandly in Harbin from July 26 to 28. The conference aimed to provide a platform for in-depth learning and extensive exchange among experts and scholars in the field of hematological tumors. On this occasion, "Oncology Frontier - Hematology Frontier" invited Dr. Shuhua Yi from the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences , to discuss topics related to Waldenström macroglobulinemia (WM) in an in-depth academic exchange.Oncology Frontier – Hematology Frontier: Waldenström macroglobulinemia is a rare B-cell lymphoplasmacytic lymphoma often accompanied by various complications. Could you introduce the main challenges faced in diagnosing and treating WM?
Dr. Shuhua Yi: Waldenström macroglobulinemia (WM) is a rare indolent lymphoplasmacytic lymphoma characterized by monoclonal IgM production and is listed as a rare disease in China. Several challenges are faced in diagnosing and treating this disease. Firstly, recognizing and accurately diagnosing WM is challenging. A comprehensive evaluation that includes immunophenotyping, genetic testing, affected sites, and clinical characteristics is required. Diagnosis cannot rely on a single indicator, making the process complex and difficult.
Secondly, there is no fixed treatment model for WM. Although some recommended treatment plans exist, the specific choice must be based on the individual characteristics of the patient, such as clinical and biological features and physical condition. This diversity presents significant challenges for clinicians, who often seek clear and definitive treatment recommendations. However, for this rare disease, doctors must adapt and meticulously adjust treatment plans to ensure their effectiveness.
Moreover, WM patients are often elderly and may have multiple comorbidities such as hypertension, diabetes, and coronary artery disease. Integrating treatment for these comorbidities into the overall treatment plan is a delicate balancing act. Doctors need to ensure efficacy while minimizing side effects, requiring strong disease management and comprehensive balancing skills.
In summary, WM presents numerous challenges in diagnosis, treatment, and patient management, necessitating deep professional knowledge and extensive clinical experience to effectively handle these complex and variable situations.
Oncology Frontier – Hematology Frontier: Looking back over the past year, what do you think is the most remarkable progress in the field of WM diagnosis and treatment? How do these advances improve patient prognosis and quality of life?
Dr. Shuhua Yi: As a rare indolent mature B-cell lymphoma, WM has seen significant advancements in treatment in recent years. The discovery and development of numerous new drugs and targets have opened new treatment pathways. Firstly, the introduction of BTK inhibitors has shown exceptional efficacy in treating WM. Several BTK inhibitors are now on the market and widely used clinically. Notably, ibrutinib and zanubrutinib have been included in the medical insurance reimbursement list, greatly alleviating the financial burden on patients and significantly improving treatment accessibility.
Additionally, research on BCL2 inhibitors has made notable progress, offering an important alternative for patients who fail BTK inhibitor treatment. Exploration of new targets, including the next generation of non-covalent BTK inhibitors that bind non-covalently to the BTK kinase without relying on the C481 site, provides more treatment possibilities. Emerging targets like mTOR have also shown promising therapeutic effects.
Moreover, advancements in immunotherapy, particularly CAR-T therapy, have brought unprecedented hope to WM treatment. Although CAR-T therapy has demonstrated efficacy in various diseases, data on its use in WM have been scarce. However, some high-quality studies emerged this year, filling this gap and confirming the significant efficacy of CAR-T therapy in WM, providing new treatment options for patients. These advancements bring more hope and anticipation for WM patients.
Oncology Frontier – Hematology Frontier: Could you share some unique experiences from China in diagnosing and treating WM? How were these experiences formed, and do they have international relevance?
Dr. Shuhua Yi: Despite China’s relatively late start in diagnosing and treating WM, its development has been rapid. Firstly, China has established standardized diagnostic and differential diagnosis processes for WM, providing a unified standard for nationwide peers to standardize the diagnosis and treatment process. This unique process is pioneering internationally, highlighting the outstanding contributions and leading position of Chinese scholars in this field.
Secondly, while continuous BTK inhibitor therapy is considered essential in international guidelines, long-term drug use often comes with adverse effects. Thus, avoiding medication if possible is advisable. Chinese experts are exploring limited-cycle treatment strategies, such as stopping BTK inhibitors after one to two years of treatment. To clarify and optimize this strategy, Chinese experts have conducted extensive explorations, including combinations with ixazomib, the BR regimen (bendamustine + rituximab), and combinations of anti-CD20 monoclonal antibodies with steroids. These explorations significantly promote the field’s development and aim to find more scientific, reasonable, and limited-cycle treatment plans to reduce the economic and psychological burden of long-term medication on patients. Chinese scholars have made indispensable contributions in this cutting-edge field.
Moreover, Chinese scholars have achieved remarkable results in mechanistic research. Through advanced technologies such as single-cell sequencing, multiple research teams have identified characteristic cell types, providing crucial research directions for overcoming WM resistance and transforming it into a controllable and curable disease. In terms of efficacy evaluation, we have found that minimal residual disease (MRD) status is an excellent indicator for assessing efficacy, significantly improving the accuracy of remission evaluation. This discovery places China at the forefront of efficacy evaluation internationally. Looking ahead, the achievements of Chinese scholars in WM will become increasingly significant, and the future development of this field holds immense promise.
Oncology Frontier – Hematology Frontier: How do you view the future development of the WM diagnosis and treatment field? What areas do you think will become research hotspots or innovation points in the coming years? How will China play a larger role in the global WM diagnosis and treatment field?
Dr. Shuhua Yi: In the field of WM diagnosis and treatment, China, with the steadfast support and deep trust of its patients, has undertaken extensive and in-depth research. Particularly, the ongoing molecular analysis research suggests the potential for further enhancing diagnostic precision and convenience in the future, offering higher-quality diagnostic services for patients.
The second important aspect is the in-depth exploration of combination therapies, focusing on optimizing and discovering new combination regimens. Among these, a novel lenalidomide-containing combination regimen is particularly noteworthy, showing promising therapeutic potential and currently unreported internationally. Future treatment of relapsed and refractory patients will offer broad exploratory space for new drug trials and combination therapies, providing more high-quality and diverse treatment options for patients.
Furthermore, we aspire to transform WM, traditionally considered incurable, into a curable disease. We hope that after a period of treatment, patients can achieve a disease-free survival period of 5 to 6 years or even longer, enjoying a “drug holiday” without medication intervention during this valuable time. This is a highly desirable vision, and we eagerly hope to extend the duration of the “drug holiday” as long as possible, bringing more hope to patients.
For advanced patients, China currently offers a wealth of cellular therapy options, including both commercial CAR-T therapies and numerous research-based CAR-T therapies at relatively affordable prices. These therapies provide valuable treatment opportunities for advanced patients and those with disease transformation, rekindling hope for many seemingly hopeless patients. With deeper understanding and continuous breakthroughs in disease mechanisms, we firmly believe that the existing diagnostic and treatment challenges will eventually be overcome.
Shuhua Yi
- MD, Chief Physician, Doctoral Advisor
- Director, Lymphoma Diagnosis and Treatment Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences
- National Clinical Research Center for Hematological Diseases
- Indolent Lymphoma Research Center
- Member, 11th Committee on Lymphocytic Diseases, Hematology Branch, Chinese Medical Association
- Member, 6th Committee, Hematological Oncology Professional Committee, Chinese Anti-Cancer Association, and Academic Secretary
- Founding Executive Committee Member and Secretary-General, Hematological Oncology Integration and Rehabilitation Professional Committee, Chinese Anti-Cancer Association
- Head, Chinese Waldenström Macroglobulinemia Working Group
- Deputy Head, Chinese Follicular Lymphoma Working Group
- Member, Hematology Immunology Branch, Chinese Society of Immunology
- Member, Hematological Immunology Group, Chinese Society of Experimental Hematology
- Chair-Elect, Hematological Oncology Professional Committee, Tianjin Anti-Cancer Association
- Member, Lymphoma Professional Committee, Tianjin Anti-Cancer Association
- Member, 1st Committee, Hematology Professional Committee, Tianjin Medical Health Association
- Director, Tianjin Hematology and Regenerative Medicine Association
- Young Member, Professional Committee, Tianjin Association of Integrative Medicine
- Authored multiple lymphoma diagnosis and treatment guidelines and expert consensus documents
- Expert Contributor, International Waldenström Macroglobulinemia Expert Consensus
- Editorial Board Member, “Chinese Journal of Clinical Oncology,” “Leukemia & Lymphoma,” and “Blood and Genomics”
