Relapsed/refractory multiple myeloma (RRMM) remains a major clinical challenge due to treatment resistance and poor prognosis, underscoring the urgent need for novel drugs and innovative therapeutic strategies. At the 2025 Annual Meeting of the American Society of Hematology (ASH), Professor Chen Wenming and his team from Beijing Chaoyang Hospital, Capital Medical University presented multiple innovative studies involving bispecific antibodies, the novel agent Eprenetapopt-like TRAIL agonist (Epnamin), and the application of mass spectrometry in minimal residual disease (MRD) monitoring.These studies offer new insights into both the treatment and precision assessment of multiple myeloma, marking significant advances in clinical management and response evaluation. During the meeting, Oncology Frontier – Hematology Frontier invited Professor Chen for an in-depth interpretation of these cutting-edge research findings.
Oncology Frontier – Hematology Frontier:
At ASH this year, your team presented several studies, including those on GR1803 and Apo-KT-DECP, focusing on patients with relapsed/refractory multiple myeloma (RRMM) and extramedullary disease (EMD). Could you summarize the key innovations and clinical significance of these studies?
Professor Chen Wenming:
At this year’s ASH meeting, our team presented multiple research projects. One focused on a bispecific antibody targeting GPRC5D and BCMA in patients with RRMM who had received four or more prior lines of therapy. Although the sample size was relatively small, this bispecific antibody demonstrated clear advantages over currently approved agents in terms of overall response rate (ORR) and very good partial response (VGPR) rate.
Notably, efficacy was particularly pronounced in the subgroup of patients with plasmacytomas. At present, we have only short-term efficacy data, and longer follow-up is required to determine progression-free survival (PFS) and to compare outcomes with existing standard therapies. The phase I trial has been completed and is currently in follow-up, while phase II enrollment has concluded. Primary phase II data are expected to be released in 2026.
Another study involved Epnamin (injectable recombinant allosteric human tumor necrosis factor–related apoptosis-inducing ligand), an innovative agent independently developed in China. It is currently the world’s first and only approved death receptor (DR4/DR5) agonist. Epnamin has been approved for the treatment of RRMM, and its clinical use in China is gradually expanding.
At present, Epnamin is mainly used in patients with RRMM complicated by plasmacytomas, typically in combination with cytotoxic agents and proteasome inhibitors. This combination therapy has demonstrated remarkable clinical efficacy, often leading to complete resolution of plasmacytomas within one to two treatment cycles.
In this report, we further explored optimal combination strategies involving Epnamin. Preliminary data suggest that Epnamin combined with proteasome inhibitors and cytotoxic agents is particularly effective in patients with plasmacytomas, achieving complete response rates of 70–80% and significantly prolonging PFS. These findings are highly meaningful for patients with advanced RRMM who are refractory to conventional therapies and demonstrate promising therapeutic potential.
Oncology Frontier – Hematology Frontier:
In the phase I dose-expansion study of GR1803, your team observed notable efficacy in patients with extramedullary multiple myeloma (EMM). Could you elaborate on the efficacy profile and tolerability of GR1803 in this patient population?
Professor Chen Wenming:
Among patients with relapsed/refractory multiple myeloma, a large proportion present with plasmacytomas. In this study, the BCMA × CD3 bispecific antibody GR1803 demonstrated comparable ORR in patients with and without plasmacytomas. However, patients with plasmacytomas showed relatively lower depth of response, defined as partial response (PR) or better.
Therefore, longer-term follow-up is needed for this subgroup. Based on our current observations, the depth of response to bispecific antibodies tends to improve with prolonged treatment duration.
Despite having more aggressive disease and poorer baseline conditions, patients with plasmacytomas tolerated bispecific antibody therapy well. Importantly, the safety profile of GR1803 was similar regardless of the presence of plasmacytomas, with no significant differences in adverse events observed between the two groups.
Oncology Frontier – Hematology Frontier:
In the phase II Apo-KT-DECP study, most patients were high-risk, triple-refractory, or had bulky EMD. The regimen showed rapid onset of action, deep responses, and relatively low toxicity. Could you discuss the clinical advantages and future prospects of this regimen?
Professor Chen Wenming:
Epnamin is a Class 1 innovative anti–multiple myeloma agent independently developed in China. It induces tumor cell apoptosis by binding to death receptors DR4 and DR5. As an apoptosis-inducing agent, it has strong mechanistic synergy with proteasome inhibitors and cytotoxic chemotherapy.
In earlier clinical trials, Epnamin was administered for five consecutive days per cycle. However, we found that this schedule was insufficient to maintain efficacy in the later phase of each treatment cycle. Accordingly, we optimized the regimen by administering Epnamin for three days in the early phase and an additional three days later in the cycle, ensuring sustained antitumor activity throughout treatment.
At the same time, given the toxicity associated with combination chemotherapy, we optimized both the dosing and administration schedules of cytotoxic agents. These adjustments significantly reduced treatment-related toxicity while further enhancing efficacy.
Current data indicate that the combination of Epnamin with carfilzomib, thalidomide, dexamethasone, and cytotoxic agents (cyclophosphamide, etoposide, and cisplatin) is highly effective. Some patients achieved complete remission after just one to two treatment cycles, and with intensified treatment, the duration of response was significantly prolonged—exceeding one year without relapse in certain cases. Overall, this optimized regimen demonstrates strong clinical applicability and value.
Oncology Frontier – Hematology Frontier:
Regarding MALDI-TOF mass spectrometry, your research suggests high concordance with next-generation flow (NGF) for MRD monitoring and the ability to distinguish daratumumab from M-protein. What transformative impact do you foresee this technology having on the clinical management of multiple myeloma?
Professor Chen Wenming:
With the continuous development of novel therapies for multiple myeloma and steadily improving treatment outcomes, there is an urgent need for more sensitive and reliable tools to assess therapeutic response. Traditional response evaluation relies primarily on serum free light chains and immunofixation electrophoresis, both of which have limited sensitivity.
We have now entered the era of minimal residual disease (MRD) assessment. Common MRD detection methods include next-generation flow (NGF) and next-generation sequencing (NGS), both of which require bone marrow sampling. However, due to the uneven distribution of myeloma cells within the bone marrow, sampling bias and false-negative results remain significant concerns.
Recently, mass spectrometry has been increasingly used internationally to detect immunoglobulins (M-protein) produced by plasma cells in peripheral blood. Compared with conventional free light chain assays and immunofixation, mass spectrometry offers superior sensitivity and accuracy for detecting M-protein in peripheral blood. This technology has already been widely adopted in the United States, and in China we are actively exploring its application for peripheral blood M-protein detection and MRD assessment.
If peripheral blood–based mass spectrometry can reliably replace bone marrow–based MRD testing, patients would no longer require bone marrow aspiration, significantly reducing discomfort while also avoiding the limitations associated with heterogeneous bone marrow involvement. Peripheral blood, with its more uniform distribution, represents a more ideal alternative sample source.
Our preliminary data show a high degree of concordance between peripheral blood and bone marrow assessments. With further validation, mass spectrometry–based detection of peripheral blood M-protein may replace bone marrow plasma cell analysis, enabling more effective response assessment, lowering testing costs, reducing patient burden, and advancing precision evaluation in clinical practice.
Expert Profile
Professor Chen Wenming, MD, PhD
Beijing Chaoyang Hospital, Capital Medical University
- Chief Physician, Professor, Doctoral Supervisor
- Department of Hematology, Beijing Chaoyang Hospital
- Lead Specialist, Beijing Municipal “Summit Talent” Team and Key Multiple Myeloma Program
- Member, International Myeloma Working Group (IMWG)
- Standing Committee Member, Asian Myeloma Network (AMN)
- Standing Director, Chinese Medical Education Association;
Chair, Hematology Professional Committee - Vice President, Beijing Public Health Science Popularization Association
- Vice Chair, Myeloma Expert Committee, Chinese Medical Doctor Association
- Deputy Head, China Autologous Stem Cell Transplantation Working Group
- Standing Committee Member, Hematologic Immunology Branch, Chinese Society of Immunology
- Standing Committee Member, Hematology Branch, Chinese Geriatrics Society
- Standing Committee Member, CSCO Anti-Leukemia Alliance
- Standing Committee Member, Hematologic Malignancies Committee, Chinese Anti-Cancer Association
- Standing Member, Hematology Institutions Branch, Chinese Hospital Association
- Member, Integrative Hematology Committee, Chinese Medical Doctor Association
- Member, Hematopoietic Stem Cell Transplantation Group, Chinese Medical Association
- Member, Hematology Committee, Cross-Strait Medical Association
Professor Chen has received funding from two National Major Science and Technology Projects, the National Natural Science Foundation of China, the Beijing Natural Science Foundation, and more than ten other grants. He has published over 300 academic papers, served as chief editor of three monographs, chief translator of one, chief editor of two textbooks, and contributor to multiple textbooks and academic volumes.
