Editor’s Note: From March 2nd to 3rd, 2024, the “Seventh Beijing Thrombosis and Hemostasis Conference and the Fifth Beijing Hematology Oncology and Immunology Summit Forum” was successfully held in Beijing. The event was organized by the National Clinical Research Center for Hematologic Diseases – Peking University Institute of Hematology and the Chinese Academy of Medical Sciences Peking Union Medical College Hospital. Numerous domestic and international hematological experts shared the latest advancements in the treatment of coagulopathy and malignant hematologic diseases through keynote reports, paper exchanges, case displays, and panel discussions. During the conference, Oncology Frontier – Hematology Frontier had the privilege of interviewing Professor Hongyan Tong from the Hematology Department of the First Affiliated Hospital of Zhejiang University School of Medicine. Professor Tong discussed the latest research developments, current challenges, and treatment strategies for Myelodysplastic Syndromes (MDS), which we summarize as follows.
Oncology Frontier – Hematology Frontier: Can you detail the recent advances in the treatment of Myelodysplastic Syndromes (MDS)?
Professor Hongyan Tong: Myelodysplastic Syndromes (MDS), currently also referred to as “myelodysplastic neoplasms,” are a group of highly heterogeneous hematologic malignancies originating from myeloid cells. In terms of treatment, the progress in managing MDS is largely based on a deeper understanding of the disease. As mentioned in the “2022 5th Edition of the WHO Classification of Haematolymphoid Tumours (WHO-HAEM5)”, the classification of MDS should be based on molecular characteristics, including subtypes like MDS with isolated del(5q) (MDS-5q), MDS with SF3B1 mutation (MDS-SF3B1), and MDS with TP53 mutation and bi-allelic inactivation (MDS-biTP53). While these subtypes have been identified, there is still a need for more precise molecular classifications to overcome the therapeutic challenges posed by the heterogeneity of MDS. It is crucial to explore and understand the molecular biological characteristics of MDS further, which could lead to the identification of more subtypes and allow for targeted treatments that improve outcomes.
Furthermore, treatment decisions for MDS should be based on risk stratification, which significantly influences the appropriateness of treatment approaches. The IPSS and IPSS-R have been used for many years, and now a new molecular-based MDS risk stratification system, IPSS-M, has been introduced. This system includes gene mutations closely associated with MDS prognosis, providing more precise risk categorization into six groups: very low, low, intermediate-low, intermediate-high, high, and very high risk. For instance, patients in the very low-risk group have a median survival time (mOS) of up to 10 years, whereas those in the very high-risk group have an mOS of about one year, highlighting significant prognostic differences. Therefore, it is essential to select appropriate treatment strategies based on the different risk levels in MDS patients.
Additionally, for lower-risk MDS patients, particularly older ones, who have a longer survival expectancy, current treatment advances focus on how to improve patients’ blood counts and delay disease progression. The main directions of research include:
1. Treatment for MDS patients with anemia focuses on Luspatercept, which has proven to be a key drug. Both the MEDALIST and COMMANDS studies (the latter a head-to-head study with EPO) have shown that Luspatercept can help more patients become transfusion-independent and maintain stable hemoglobin levels.
2. At our center, combining EPO with Luspatercept in treating MDS has shown to further improve efficacy, helping patients become free from transfusion dependence.
3. For MDS patients with thrombocytopenia, thrombopoietin receptor agonists (TPO-RAs) have demonstrated good efficacy and safety, with about 50% of patients showing improved platelet levels after treatment.
4. Cyclosporine may be used for patients with hypoproliferative MDS. However, it should be noted that if such younger MDS patients do not see a significant improvement in transfusion dependency within six months, it is recommended they undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) treatment.
Lastly, the treatment of higher-risk MDS remains a major focus. Since its characteristics are very close to acute myeloid leukemia (AML), many new AML drugs are also being used to treat high-risk MDS. Key research advancements include:
1. At the 2023 ASH conference, the BCL-2 inhibitor Venetoclax achieved high remission rates in MDS treatment, especially when combined with azacitidine (VEN-AZA) in pre-transplant bridging therapy for high-risk MDS, exploring whether this combination can maximally reduce MDS clones and achieve low relapse rates post-transplant.
2. Immune checkpoint inhibitors have also made some progress; new CD47 monoclonal antibodies in several multicenter studies have shown that they can achieve good complete remission rates (CR) for high-risk MDS, although whether this translates to extended survival is still under investigation.
3. Targeted drugs for specific genetic mutations also hold promising prospects, such as IDH1/2 mutation inhibitors, which are orally safe and can provide adequate treatment for chronic myeloid malignancies, especially in elderly MDS patients. Additionally, CD3/CD123 bispecific antibodies have shown good therapeutic effects for high-risk MDS patients, achieving very high CR rates.
Overall, because of the high heterogeneity of MDS, treatment breakthroughs are challenging. However, I believe that with continued deepening of our understanding of MDS, the discovery of new treatment targets and novel targeted drugs, combined with allogeneic hematopoietic stem cell transplantation (allo-HSCT), the effectiveness and survival of MDS treatments can be further improved.
Oncology Frontier – Hematology Frontier: What are the current bottlenecks in MDS treatment?
Professor Hongyan Tong: The biggest bottleneck in MDS treatment currently lies in how to effectively improve overall survival (OS). As early as 2004, the approval of hypomethylating agents (HMAs) was significant for MDS treatment. Before their availability, treatment options for MDS were extremely limited, and most patients could only receive supportive care or treatments borrowed from AML therapies (but only low-intensity chemotherapy). In this context, the overall survival of MDS patients was very poor, especially for high-risk MDS patients. While the advent of HMAs has shown benefits over previous best treatments, it is somewhat disappointing that nearly 20 years of HMA application in the real world has not improved the overall survival of MDS, which is one of the pain points in MDS treatment. Today, the ultimate goal of many new MDS treatments is still to improve patient survival, a critical breakthrough that urgently needs to be addressed.
Oncology Frontier – Hematology Frontier: Could you discuss current treatment recommendations that can effectively improve the survival of MDS patients?
Professor Hongyan Tong: First and foremost, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a very mature treatment that clearly improves the survival of MDS patients. For younger high-risk MDS patients, allo-HSCT has achieved a three-year overall survival rate of 70%. Secondly, with the deepening understanding of MDS, combinations of new targeted drugs such as BCL-2 inhibitors, CD47 monoclonal antibodies, and CD3/CD123 bispecific antibodies hold promising prospects and are current hot topics in research. I believe that the future will see the emergence of even more novel targeted drugs, leading to breakthroughs in MDS treatment.
Professor Hongyan Tong
– PhD, Chief Physician, Doctoral Supervisor
– Executive Director of the Department of Hematology, the First Affiliated Hospital of Zhejiang University School of Medicine
– Director of the Myelodysplastic Syndromes Center and the Lymphoma Center
– Deputy Director of the Zhejiang Provincial Clinical Research Center for Hematologic Diseases
– Head of the Diagnostic Teaching and Research Department, Zhejiang University School of Medicine
– Zhejiang Provincial Health Leadership Talent
– Zhejiang Provincial High-level Innovative Talent
– Zhejiang Province’s New Century 151 Talent
– Recipient of the Zhejiang Provincial Outstanding Young Talent Project
– Senior Visiting Scholar at the Royal Free Hospital, UK
**Societal Roles:
– Member of the Erythrocyte Group, Hematology Branch, Chinese Medical Association
– Executive Member and Leader of the MDS/MPN Study Group, Clinical Oncology Hematology Lymphoma Committee of the Chinese Medical Women’s Doctor Association
– Deputy Leader of the MDS/MPN Working Group, Hematologic Oncology Committee of the Chinese Anti-Cancer Association
– Executive Member and Deputy Director of the MDS Working Committee, Hematology Branch of the Chinese Geriatrics Society
– Leader of the MDS/MPN Study Group, Hematology Physician Committee of the Zhejiang Provincial Medical Association
– Deputy Director of the Hematology Lymphoma Professional Committee of the Zhejiang Anti-Cancer Association
– Vice Chairperson of the Clinical Trial and Ethics Branch, Zhejiang Medical Association
– Vice Chairperson of the Hematology Branch, Zhejiang Medical Association
– Principal Investigator of 5 National Natural Science Foundation of China projects and 7 provincial key projects including Outstanding Youth projects. Published over 50 papers as the first or corresponding author in SCI journals such as Haematologica, European Journal of Cancer, J Infect. First author of two provincial scientific and technological progress second prizes, co-contributor to one national scientific and technological progress second prize and six provincial scientific and technological progress first and second prizes.
