From March 23rd to 24th, 2024, the 15th Academic Conference of the Chinese Medical Association’s Experimental Diagnosis Hematology Branch and the First Academic Conference on Rare Blood Diseases, hosted by the Chinese Medical Association and the Hematology Branch of the Chinese Medical Association, and co-organized by the First Affiliated Hospital of Soochow University, was successfully held in Suzhou, Jiangsu Province, China. Numerous hematological experts and scholars from China and abroad gathered to exchange academic insights on the experimental diagnosis of hematological diseases and advancements in the field of rare blood diseases. Oncology Frontier – Hematology Frontier had the privilege of interviewing Professor Chunyan Sun from Tongji Medical College, Huazhong University of Science and Technology, affiliated with Union Hospital, to discuss the application of peripheral blood circulating plasma cell detection in multiple myeloma (MM).
Oncology Frontier – Hematology Frontier: With the continuous emergence of new drugs and improvements in diagnostic methods, the diagnosis and treatment of MM have been continuously enhanced and refined in recent years. Could you please introduce the latest developments in the diagnosis and treatment of MM in recent years?
Professor Chunyan Sun: In the field of multiple myeloma treatment, with the widespread use of proteasome inhibitors and immunomodulatory agents, CD38 monoclonal antibodies have become readily available frontline drugs, greatly improving the efficacy of multiple myeloma patients. On the basis of these drugs, new drugs have also emerged in recent years, including novel proteasome inhibitors, immunomodulatory agents, and continuously developing new CD38 monoclonal antibodies.
Among all the treatment advancements, immunotherapy, especially the progress of bispecific antibodies, is worth noting. Particularly, bispecific antibodies targeting B-cell maturation antigen (BCMA) and CD3 have made significant progress in recent years. Furthermore, GPRC5D×CD3 bispecific antibodies have shown promising efficacy in patients with poor response to BCMA-targeted bispecific antibody treatment. In addition to these, other immunotherapeutic drugs such as antibody-drug conjugates (ADCs) have also demonstrated therapeutic potential in the treatment of multiple myeloma, especially in the treatment of relapsed/refractory multiple myeloma (RRMM). However, the toxic side effects brought about by these drugs, such as corneal lesions, are also worth noting. In the future, while improving efficacy, reducing toxic side effects as much as possible remains a focus of clinical research.
Another very important direction is CAR-T cell immunotherapy. Currently, CAR-T cell immunotherapy is rapidly developing in China, including CAR-T targeting BCMA and other targets, as well as bispecific CAR-T or sequential CAR-T therapy, which have achieved very high response rates and long progression-free survival (PFS) and overall survival (OS) in RRMM and high-risk MM. Therefore, I believe that CAR-T cell immunotherapy may gradually change the treatment landscape of multiple myeloma in the future. In addition to immunotherapeutic drugs, various new drugs are also under development, including small molecule inhibitors, targeted drugs, and drugs with new mechanisms of action. With further research and combination applications of these therapeutic drugs, MM is expected to become a chronic tumor that can be cured in the future.
Oncology Frontier – Hematology Frontier: During this conference, you shared insights on “The Application of Peripheral Blood Circulating Plasma Cell Detection in MM.” Could you discuss the significant implications of peripheral blood circulating plasma cell detection for the diagnosis, treatment, and prognosis of MM?
Professor Chunyan Sun: Peripheral blood circulating plasma cell detection involves detecting plasma cells in the peripheral blood to assess tumor burden. As an emerging technology, the main advantage of peripheral blood circulating plasma cell detection lies in its non-invasiveness. In the field of hematological malignancies, especially lymphoma, liquid biopsy has made significant progress. In recent years, there has been considerable attention and important advancements in the study of circulating plasma cells in multiple myeloma (MM). The application of circulating plasma cells in plasma cell malignancies includes various aspects such as screening for plasma cell diseases. Studies have found that circulating plasma cells can be detected at various stages of plasma cell diseases, including isolated plasmacytoma, monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma, and MM, albeit with differences in detection frequency and median circulating plasma cell count.
Another important application of circulating plasma cells is their use in stratified diagnosis of plasma cell diseases. Multicenter studies in Europe have confirmed the importance of circulating plasma cell counts in identifying high-risk smoldering myeloma. Additionally, researchers have proposed a new prognostic stratification model for smoldering myeloma, incorporating circulating plasma cell counts, replacing the previous bone marrow plasma cell ratio. This new model relies entirely on peripheral blood indicators for assessment, achieving non-invasive monitoring. With further confirmation in the future, it may have significant clinical value.
Furthermore, the level of circulating plasma cells is also of significant value for risk stratification in newly diagnosed myeloma. Multiple clinical studies have confirmed this, and the European Myeloma Network recommends circulating plasma cell detection as an indicator for risk stratification in newly diagnosed myeloma. At the 2023 American Society of Hematology (ASH) Annual Meeting, there were also two oral presentations on circulating plasma cells, emphasizing the importance of high or low circulating plasma cell counts detected by new second-generation flow cytometry methods for prognosis assessment. It was also pointed out that patients with newly diagnosed myeloma without circulating plasma cells may represent a unique clinical subtype with a favorable prognosis. These findings are worth focusing on in the future.
Oncology Frontier – Hematology Frontier: What are the methods for peripheral blood circulating plasma cell detection? From an international perspective, which treatment methods are expected to become the mainstay of future clinical applications?
Professor Chunyan Sun: Methods for detecting peripheral blood circulating plasma cells include peripheral blood smears, flow cytometry methods including multiparameter flow cytometry and the commonly used second-generation flow cytometry abroad, as well as second-generation sequencing, among others. Different detection methods have different sensitivities: the sensitivity of peripheral blood smears is 1%, multiparameter flow cytometry can achieve sensitivities of 10^-4 to 10^-5, second-generation flow cytometry can achieve sensitivities of 10^-5 to 10^-6, and second-generation sequencing can also achieve sensitivities of 10^-5 to 10^-6.
From the trends in domestic and international research, the most widely used method in clinical practice currently is flow cytometry, including multiparameter flow cytometry and second-generation flow cytometry. The latest research abroad tends to favor the use of second-generation flow cytometry due to its higher sensitivity. However, in China, multiparameter flow cytometry is more commonly applied because second-generation flow cytometry is not yet widely available. Multiparameter flow cytometry can achieve sensitivities of 10^-4 to 10^-5, and with the appropriate antibody combinations and cut-off values, it can also play an important role in the diagnosis, prognosis, and monitoring of patients.
At present, our center is also conducting multiparameter flow cytometry detection of circulating plasma cells and has initiated multicenter clinical studies to explore the application of multiparameter flow cytometry in newly diagnosed myeloma patients. Through standardized antibody combinations, uniform cut-off values, and validation in large samples, we hope to establish better antibody combinations and cut-off values suitable for the Chinese population in the future.
Deputy Director of Hematology Department, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Level Three Professor, Chief Physician, Ph.D. Supervisor
Standing Committee Member of the Hematologic Oncology Professional Committee of the Chinese Anti-Cancer Association
Young Member of the Hematology Branch of the Chinese Medical Association
Member of the Plasma Cell Group of the Hematology Branch of the Chinese Medical Association
Member of the Experimental Diagnosis Group of the Hematology Branch of the Chinese Medical Association
Member of the Hematologic Malignancies Transformation Committee of the Chinese Anti-Cancer Association
Deputy Leader of the Chinese Hemoglobinopathy Group
Standing Committee Member of the Hematology Professional Committee of the China Medical Education Association
Vice Chairman of the Myeloma Branch of the China Medical Education Association
Chairman of the Translational Medicine Professional Committee of the Hubei Medical Biomedical Immunology Association
Chairman of the Young Committee of the Hematologic Diseases Professional Committee of the Wuhan Medical Association
Communicating Editor of the Chinese Journal of Hematology
Principal Investigator of 5 National Natural Science Foundation projects
Published over 110 papers in authoritative domestic and international journals, including more than 60 SCI papers
Recipient of the first prize for Scientific and Technological Progress in Hubei Province in 2007, 2012, and 2020
