Editor's Note: CAR-T therapy and bispecific antibodies, two innovative immunotherapies, have shown significant efficacy in patients with relapsed/refractory multiple myeloma (RRMM). But how do these two therapies compare in clinical practice? Minimal Residual Disease (MRD) detection is an important tool for evaluating treatment response and prognosis in multiple myeloma (MM), but its application in clinical settings is still limited. How can MRD use be further promoted? At the recent European Society for Medical Oncology (ESMO) Congress 2024, two pivotal studies delved into these questions, sparking widespread attention. This article features insights from Dr. Zhen Cai of The First Affiliated Hospital of Zhejiang University School of Medicine on these studies.

Study 1：Real-World Comparison of BCMA-Bispecific Antibodies and CAR-T Therapy in MM Survival Outcomes

Dr. Zhen Cai:

MM treatment has entered the immunotherapy era, with CAR-T therapy and bispecific antibodies offering remarkable efficacy and similar indications. However, these two treatments differ in administration, treatment protocols, and applicable scenarios. The choice between CAR-T and bispecific antibodies involves considering factors like treatment accessibility, MM characteristics, and patient-specific factors.

This study utilized the TriNetX database to analyze survival outcomes in MM patients receiving either BCMA-bispecific antibodies or CAR-T therapy in real-world settings. Results showed that BCMA CAR-T therapy offered a survival advantage over bispecific antibodies. Subgroup analysis highlighted that BCMA CAR-T conferred greater survival benefits, particularly in older patients and those without prior bone marrow transplants. With the aging population, MM is becoming a prominent health issue, and CAR-T therapy may present new options for this demographic.

In addition, several novel drugs are in clinical development, including four BCMA-targeting bispecific antibodies, two GPRC5D bispecifics, and one FcRH5 bispecific. Current trials are exploring combinations of bispecific antibodies with other therapies, such as immunomodulators (IMiDs), proteasome inhibitors (PIs), and CD38 antibodies. There is even ongoing research on combining bispecifics with each other, potentially offering new hope for MM patients. As new drugs emerge and clinical practitioners continue their efforts, the path toward functional cure for MM appears increasingly promising.

Study 2：Ultra-Sensitive cfDNA Analysis for MRD Detection and Subtyping in MM

Dr. Zhen Cai:

MRD detection in MM is crucial for assessing treatment response and prognosis, enabling detection of malignancy at levels far below traditional morphological techniques. MRD serves as a commonly used indicator of tumor burden, reflecting treatment response and serving as a prognostic tool for future relapse. With the advent of new drugs, the depth of MM treatment responses has improved significantly, yet traditional evaluation criteria have limitations in accurately reflecting these advancements. Therefore, MRD detection has become increasingly relevant in MM clinical management.

Traditional MRD detection focuses on the bone marrow (BM) using techniques such as next-generation flow cytometry (NGF) and next-generation sequencing (NGS). Although sensitive, these methods are invasive, making frequent monitoring challenging.

This study introduced two highly sensitive techniques—CloneSight and BloodFlow—to monitor peripheral blood (PB) MRD in MM patients. The study analyzed the concordance between CloneSight and BloodFlow with BM MRD, as well as their positive predictive value (PPV) and negative predictive value (NPV). Findings showed that CloneSight’s high PPV makes it possible to further evaluate PB-MRD in patients with BM-MRD negativity, identifying patients at immediate risk of relapse. Compared to BM-MRD, PB-MRD testing is less invasive, allowing for broader clinical application. This innovation not only enriches the monitoring tools available for MM but also provides a new avenue for MRD monitoring advancements.

While the study lays a foundation for PB-MRD in MM, further research is necessary to explore PB-MRD’s dynamic changes across various treatment contexts, as well as its association with other clinical prognostic indicators, such as biomarkers and genetic characteristics. Although CloneSight and BloodFlow offer high sensitivity, their accuracy can be affected by sample handling and technical factors, so strict experimental control is essential to ensure reliable and reproducible results.

In summary, this study introduces PB-MRD detection technologies like CloneSight and BloodFlow, providing new tools for MM monitoring and management. Despite certain limitations and challenges, the study injects fresh momentum into MM clinical research and treatment strategy optimization.

Expert Profile

Dr. Zhen Cai

MD, Zhejiang University School of Medicine, First Affiliated Hospital; Qiushi Distinguished Physician at Zhejiang University; Associate Professor (Grade II), Chief Physician, and Doctoral Advisor. Director of the Multiple Myeloma Treatment Center; High-Level Innovative Talent in Health, Zhejiang Province. Chair of the Blood and Lymphoma Specialty Committee, Zhejiang Anti-Cancer Association; Incoming Chair of the Hematology Branch, Zhejiang Medical Association; Member of the Hematology Branch of the Chinese Medical Association and Deputy Leader of the Plasma Cell Disease Group. Standing Member of the Hematologic Oncology Committee and Deputy Leader of the Multiple Myeloma Group, Chinese Anti-Cancer Association; Standing Member of the Blood Immunology Committee, Chinese Society of Immunology; Vice Chair, CSCO China Working Group on Autologous Hematopoietic Stem Cell Transplantation.