Multiple Myeloma (MM), a type of blood system cancer most commonly affecting middle-aged and elderly individuals, ranks as the second most prevalent malignant hematologic tumor. Despite significant improvements in patient remission depths through new drug combinations and autologous stem cell transplantation (ASCT), studies indicate that even patients achieving complete remission may still harbor considerable levels of tumor cells, known as minimal residual disease (MRD). Currently, methods for assessing bone marrow MRD, including multi-parameter flow cytometry (MFC) and next-generation flow (NGF), require bone marrow biopsies from MM patients. These procedures are invasive and subject to sampling bias, making sequential MRD monitoring challenging.
Recently, the team led by Gang An and Lugui Qiu at the Institute of Hematology, Chinese Academy of Medical Sciences (CAMS), published a research paper titled "Monitoring minimal residual disease in patients with multiple myeloma by targeted tracking serum M-protein using mass spectrometry (EasyM)" in Clinical Cancer Research (IF=11.5). This study is the first in China to demonstrate that mass spectrometry (MS) technology can identify the specific sequences of serum M-protein (MP) in MM patients, using them as MM-specific tumor molecular markers for targeted quantitative tracking. The sensitivity of this method is comparable to, if not better than, bone marrow NGF testing, offering a new, minimally invasive option for the clinical monitoring of MRD in MM patients.
The study incorporated 56 newly diagnosed MM patients from the national hematologic disease longitudinal cohort-multiple myeloma sub-cohort. By conducting easyM MS testing (a mass spectrometry-based protein analysis method) on the patients’ initial and sequential serum samples, it was discovered that easyM MS can identify individual-specific MP sequences, achieving high sensitivity targeted quantitative monitoring of serum MP in MM patients and predicting disease relapse/progression in advance.
Additionally, by comparing the results of easyM MS testing with those of serum immunofixation electrophoresis (IFE), bone marrow MFC (sensitivity <10^-4), and NGF (sensitivity <10^-5) performed at the same time points, it was found that MS could still detect residual MP in the peripheral serum of some patients when other testing methods returned negative results. Subsequently, using bone marrow NGF as the gold standard for MRD detection, the researchers optimized the clinical definition of the easyM MS testing negative cutoff value through receiver operating characteristic (ROC) curve analysis. Under these conditions, easyM MS demonstrated a level of detection concordance comparable to that of bone marrow NGF. Finally, through survival analysis, it was found that the optimal easyM MS status could further distinguish patient prognosis on top of the existing clinical efficacy evaluation system and is an independent prognostic factor for progression-free survival and overall survival in MM patients.
Dr. Gang An, a chief physician at the Institute of Hematology, Chinese Academy of Medical Sciences (CAMS), and Dr. Lugui Qiu, also a chief physician at the same institute, served as the co-corresponding authors for this study. Ph.D. candidates Huishou Fan and Dr. Lihui Shi, attending physicians at the Institute of Hematology, CAMS, along with Dr. Bing Wang from Shanghai Quick-seq Biotech Co., Ltd., were the co-first authors of the project. The project received funding support from the National Natural Science Foundation of China, the Medical and Health Science and Technology Innovation Project of the Chinese Academy of Medical Sciences, and a research grant from Shanghai Quick-seq Biotech Co., Ltd.
Reference:
1. Cowan AJ, Green DJ, Kwok M, Lee S, Coffey DG, Holmberg LA, Tuazon S, Gopal AK, Libby EN. Diagnosis and Management of Multiple Myeloma: A Review. JAMA. 2022 Feb 1;327(5):464-477.
2. Munshi NC, Avet-Loiseau H, Rawstron AC, Owen RG, Child JA, Thakurta A, et al. Association of Minimal Residual Disease With Superior Survival Outcomes in Patients With Multiple Myeloma: A Meta-analysis[J].JAMA Oncol.2017,3(1):28-35.
