丨 2025 International Cell & Immunotherapy Congress**
To promote innovation in China’s cell and immunotherapy fields, deepen scientific exchange, share the latest clinical research progress, and foster global collaboration and clinical translation, the 2025 International Cell & Immunotherapy Congress (CTI 2025)—jointly organized by Zhejiang University, the International Academy for Clinical Hematology (IACH), the Zhejiang Society of Immunology, and the Zhejiang Anti-Cancer Association, and co-hosted by the First Affiliated Hospital of Zhejiang University School of Medicine and the Liangzhu Laboratory—was held in Hangzhou from November 13 to 16, 2025.
During the conference, Oncology Frontier – Hematology Frontier invited Prof. Jiye Liu from the Affiliated Cancer Hospital of Shandong First Medical University to share insights on the role of monoclonal antibodies in multiple myeloma, including their core therapeutic positioning, optimal patient selection, patterns of resistance, and breakthroughs in subsequent treatment strategies.
Q1
What is the current therapeutic role of monoclonal antibodies in multiple myeloma, and which patients benefit most? How should efficacy and safety be balanced when combining monoclonal antibodies with chemotherapy or proteasome inhibitors?
Prof. Jiye Liu: At present, CD38-targeted monoclonal antibodies—particularly daratumumab and isatuximab—play a pivotal role in the treatment of multiple myeloma. Daratumumab was included in China’s National Reimbursement Drug List in 2023 and has since been widely used among Chinese multiple myeloma patients.
With the deepening of clinical research, daratumumab has firmly established itself in frontline treatment. In clinical trials, regimens combining daratumumab with proteasome inhibitors and immunomodulatory drugs have demonstrated significant efficacy, elevating daratumumab from a later-line option to a first-line therapy, thereby enabling more newly diagnosed patients to benefit. Daratumumab is also now used in maintenance therapy, further enhancing its value within the overall treatment landscape.
Moreover, the drug has shown a favorable safety profile across multiple studies. With its proven efficacy and reliable tolerability, CD38 monoclonal antibodies such as daratumumab have secured an important position in current multiple myeloma treatment algorithms.
Q2
What are the most common resistance patterns observed during monoclonal antibody therapy in multiple myeloma? Mechanistically, what factors drive resistance?
Prof. Jiye Liu: As daratumumab has become widely used, the number of patients developing resistance has gradually increased, and understanding its mechanisms has become a research priority. Resistance involves several major aspects.
First, daratumumab targets CD38 antigens on myeloma cells. Tumor cells may downregulate CD38 expression, reducing target availability and resulting in strong drug resistance.
Multiple myeloma is also highly heterogeneous. Within the bone marrow microenvironment, malignant cells with different genetic backgrounds coexist. When daratumumab eliminates sensitive clones, remaining tumor cells with specific genetic features may survive via immune escape mechanisms, thereby driving resistance.
In addition, the immunosuppressive bone marrow microenvironment is a key contributor. The antitumor effect of daratumumab depends on immune effector cells such as NK cells and macrophages. However, suppressive immune cells within the microenvironment impair these effector functions, weakening therapeutic activity and promoting resistance.
Based on these resistance mechanisms, current research is focused on reversing microenvironment-driven resistance and intervening in clonal evolution caused by genetic heterogeneity. Strategies to upregulate CD38 expression on tumor cells—thereby enhancing target visibility—are also being explored as a means to improve the efficacy of CD38 monoclonal antibody therapy.
Q3
For patients who have developed resistance to monoclonal antibodies, which treatment strategies are currently recommended? What progress has been made in overcoming resistance through new therapeutic modalities?
Prof. Jiye Liu: The therapeutic landscape for multiple myeloma has greatly expanded—from early proteasome inhibitors and immunomodulatory drugs to today’s monoclonal antibodies, bispecific or multispecific antibodies, and the rapidly progressing CAR-T cell therapies. These modalities provide a foundation for sequential therapy following resistance.
In clinical practice, once resistance occurs, the regimen can be switched to subsequent lines of treatment. For example, in daratumumab resistance, clinicians may explore mechanisms to overcome resistance using agents such as selinexor, or switch to drugs targeting alternative antigens. The most widely used target following CD38 is BCMA, which offers both bispecific antibodies and CAR-T therapies.
If resistance develops again after BCMA-directed treatment, options include therapies targeting GPRC5D—either bispecific antibodies or CAR-T—and even dual-target CAR-T constructs simultaneously targeting BCMA and GPRC5D.
Through multi-target, multi-line sequential treatment strategies, clinicians can effectively address clonal evolution and resistance, ensuring that patients continue to receive effective treatment throughout the disease course. Although multiple myeloma is not yet curable, the continued advancement of therapeutic drug development and optimization of treatment systems have significantly prolonged survival and improved quality of life. The transition of multiple myeloma toward chronic disease management is steadily progressing.
