The "7th Beijing Thrombosis and Hemostasis Conference of the Chinese Society of Immunology Hematology Branch" and the "5th Beijing Hematologic Tumor and Immunology Summit Forum" sponsored by the Chinese Society of Immunology Hematology Branch and hosted by the National Clinical Research Center for Hematologic Diseases- Peking University Institute of Hematology and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, was held in Beijing from March 1st to 3rd, 2024. During the conference, Oncology Frontier - Hematology Frontier had the honor to invite Professor Jun Ma from the Harbin Institute of Hematology and Oncology to share the development process of hematology in recent decades and advances in the treatment of hematologic tumors.Oncology Frontier – Hematology Frontier: As one of the leading figures in the field of hematologic tumors, could you please share the development process of hematology in China in recent decades and the advances in the treatment of hematologic tumors?
Professor Jun Ma: China has a long history of hematology diagnosis and treatment, and its development has been very rapid. In 1917, the Department of General Internal Medicine was established, and the diagnosis and treatment of anemia patients began. Foreign doctors also treated malignant blood patients in China. In 1938, China established specialized and sub-specialized hematology departments. Currently, hematology is developing rapidly. Through the efforts of five or six generations, it has reached the international level. Some areas have even surpassed the international advanced level. For example, the Harbin Protocol brings a cure rate of over 92% for acute promyelocytic leukemia (APL) treated with arsenic trioxide, Academician Wang Zhenyi pioneered the successful treatment of APL with all-trans retinoic acid, Academician Huang Xiaojun created the “Beijing Protocol” haploidentical transplantation, and CAR-T cell therapy has reached the international advanced level.
From the first generation of hematologists to the second generation, the development of hematologic tumors has been promoted. Professor Shen Zhixiang and I are bridging between the second and third generations because there was no further development during the ten years of the Cultural Revolution. After returning to China in the early 1980s, we continued to promote the development of hematologic tumors. Currently, we are the fifth and sixth generation scholars. Hematologic tumors have a history of nearly 107 years. We inherit the aspirations of the older generation of hematologic tumor researchers and continue to promote the development of hematology.
China’s hematologic diseases mainly include malignant blood tumors, coagulation diseases, and anemia. Malignant blood tumors are mainly divided into lymphoma, leukemia, multiple myeloma, and myelodysplastic syndromes (MDS) based on the incidence rate. With the accelerated aging of the population, the incidence of these four diseases is also increasing.
Lymphoma treatment is based on chemotherapy and also includes small-molecule or large-molecule monoclonal antibodies, ADC antibodies, or bispecific antibodies, CAR-T cell therapy, etc., which can achieve a clinical cure rate of up to 70% for B-cell lymphoma. Lymphoma is one of the fastest developing hematologic tumors in the past 30 years. 30 years ago, there were only over 200 scholars engaged in the pathology, radiotherapy, and internal medicine of lymphoma. Now, there are more than 4,000 people participating in radiation therapy, intervention, pathology, rehabilitation, etc., mainly focused on clinical hematologic tumors. Furthermore, there are sub-specialties and MDT teams. Currently, it has become one of the fastest progressing tumor fields domestically. Moreover, the cure rate of lymphoma in large tertiary hospitals in various provinces and cities can reach nearly 60%. However, Professor Zhu Jun and I have compiled data on more than 16,000 lymphoma patients nationwide and found that due to economic conditions and other reasons, the cure rate in various regions is only about 37%. Therefore, achieving the goal of increasing the five-year survival rate of tumors by 15% in “Healthy China 2030” is a daunting task. By aligning with international standards, lymphoma treatment can reach the most advanced level, allowing patients to achieve long-term survival, but we still need to work together to strive for it.
In the field of leukemia, progress has been slow in the past, but it is currently developing rapidly. From being based on chemotherapy to the current treatment strategies including hematopoietic stem cell transplantation, cell therapy, monoclonal antibodies, bispecific antibodies, small molecules, and immunosuppressants, targeted therapies such as FLT3 inhibitors for treating acute myeloid leukemia with FLT3 mutation, IDH inhibitors for treating IDH1-positive acute myeloid leukemia, and for elderly patients who cannot undergo chemotherapy, BCL-2 inhibitors combined with azacitidine can extend patients’ survival to about 13 to 18 months. Hematopoietic stem cell transplantation and cell therapy have become the main treatment options for leukemia.
The treatment of chronic leukemia has progressed rapidly. Since the approval of imatinib in 2001, the disease-free survival of chronic myeloid leukemia has reached about 88% to 90% over 20 years, and it can now be managed long-term like chronic diseases such as diabetes and hypertension. BTK inhibitors include four drugs such as “Three Bu Yi Ka”. Among them, China’s innovative drugs zebutinib and obutinib have good efficacy for small B-cell lymphomas and chronic lymphocytic leukemia. This non-chemotherapy regimen allows patients to achieve long-term survival. If combined with other targeted therapy drugs, it may achieve a curative effect for diseases such as chronic lymphocytic leukemia.
In acute lymphoblastic leukemia, the current treatment options include monoclonal antibody/bispecific ADC, cell therapy, and hematopoietic stem cell transplantation, which can achieve a cure rate of 50% in young patients, and the clinical cure rate of children’s acute lymphoblastic leukemia at high risk is around 92%. However, overall, elderly hematologic tumors are still an important issue, with low treatment and cure rates, especially for patients over 60 years old, so breakthroughs in the diagnosis and treatment of elderly leukemia are urgently needed in the future.
Although multiple myeloma cannot be cured, patients’ disease-free survival has been extended from an average of 3 years in the past to an average of about 12 years now. Current treatment strategies include first-generation/second-generation/third-generation proteasome inhibitors, first-generation/second-generation/third-generation anti-angiogenic inhibitors, ADC drugs such as CD38 monoclonal antibodies, and BCMA/CD3 bispecific antibodies, allowing patients to achieve long-term survival and even clinical cure. Although myelodysplastic syndromes progress relatively slowly among these four diseases, various monoclonal antibodies, ADCs, and small molecules are emerging, leading to rapid progress in malignant blood tumors.
In addition, for hemophilia, the introduction of foreign long-acting recombinant factors (recombinant human coagulation factor VIII-Fc fusion protein) and related antibodies have enabled hemophilia patients to lead a life with a very good quality, living as normal as other people.
Rare blood diseases are very numerous, including hundreds of subtypes, and related diagnosis and treatment have also made rapid progress. For example, Castleman’s disease can be treated with new monoclonal antibodies, neuroblastoma bone marrow metastasis has corresponding antibodies, and peripheral T-cell lymphoma, NKT lymphoma, and aspergillosis and other rare subtypes also have ADCs and small molecule drugs.
But overall, innovation leads to the future. Without the emergence of innovative drugs, there is no possibility of curing tumors. Therefore, future gene therapy, vaccine therapy, new targeted therapy, and immunotherapy should be widely valued. The goal is above life, and life is above all else. In order to achieve better long-term survival and higher clinical cure rates for hematologic tumor patients, we still need to work together and strive.
Professor Jun Ma
Chief Physician, Professor, Doctoral Supervisor
Director of Harbin Hematology Oncology Research Institute
Chairman of the Supervisory Board of the Chinese Society of Clinical Oncology (CSCO)
Vice Chairman of the Asian Society of Clinical Oncology
Chairman of the Leukemia Expert Committee of the Chinese Society of Clinical Oncology
Leader of the Expert Group on Lymphoma Specialization Project of the National Health Commission’s Capacity Building and Continuing Education Center
Editor-in-Chief of Leukemia & Lymphoma Magazine
Former Chairman of the Chinese Society of Clinical Oncology (CSCO)
Former Deputy Director of the Hematology Branch of the Chinese Medical Association
