Every March is the international “Myeloma Awareness Month”. In order to better serve patients with multiple myeloma, recently, the Hematology Department of Beijing Chaoyang Hospital, affiliated with Capital Medical University, held a series of activities for Multiple Myeloma Awareness Month. The aim is to enhance public awareness of multiple myeloma through a combination of online and offline approaches, calling for attention to the new trend of long-term survival in multiple myeloma and establishing a new concept of comprehensive management throughout the disease course. During the event, Professor Yin Wu from Beijing Chaoyang Hospital, affiliated with Capital Medical University, shared the exciting content titled “Diagnosis and Treatment Evaluation of Multiple Myeloma: Examination and Application”. Below is a summary of the presentation.
Multiple myeloma (MM) is a malignant tumor characterized by abnormal proliferation of plasma cells in the bone marrow, with the secretion of monoclonal immunoglobulin (M protein) as the main feature. Clonal proliferation of plasma cells infiltrates the bones and soft tissues, causing manifestations such as bone destruction, anemia, and kidney damage.
Diagnosis of plasma cell diseases
The diagnosis of plasma cell diseases requires three elements: clonal plasma cells, monoclonal immunoglobulin (M protein), and end-organ damage caused by plasma cells/M protein. Analysis of 45,366 patients from 1960 to 2011 conducted by the Mayo Clinic showed that common diseases associated with the appearance of M protein include monoclonal gammopathy of undetermined significance (MGUS, accounting for 57%), MM (18%), and smoldering myeloma (SMM, 4%), among others. The International Myeloma Working Group (IMWG) established diagnostic criteria for symptomatic myeloma in 2014: clonal plasma cells in the bone marrow ≥10% or biopsy-confirmed plasma cell tumor + any one of the myeloma defining events (MDE). End-organ damage caused by plasma cell proliferation includes: (1) hypercalcemia: serum calcium >0.25 mmol/L above the upper limit of normal or >2.75 mmol/L; (2) renal insufficiency: creatinine clearance rate (Ccr) <40 ml/min or serum creatinine (Cr) >2 mg/dL; (3) anemia: hemoglobin (HB) decrease >2 g/dl below the lower limit of normal or HB <10 g/dl; (4) bone lesions: >1 lytic lesions on bone X-ray, CT, or PET-CT. In addition, any of the following biological markers can diagnose “early MM”: (1) clonal bone marrow plasma cells ≥60%; (2) involved/uninvolved serum free light chain (sFLC) ratio ≥100; (3) >1 focal lesions on MRI.
1. Finding Clonal Plasma Cells – Bone Marrow Aspiration/Biopsy
Detection of clonal plasma cells can be done through bone marrow aspiration/biopsy. (1) Plasma cell quantity: Bone marrow aspiration alone may suffice, but bone marrow biopsy provides more reliable evidence of plasma cell infiltration; there is no statistical difference between bone marrow aspiration and biopsy in terms of treatment evaluation. (2) Clonality of plasma cells: Immunohistochemistry of bone marrow/tumor tissue identifies cytoplasmic monoclonal immunoglobulin to determine clonality; immunophenotyping of bone marrow/tissue can determine the clonality of plasma cells, but detection techniques are not standardized. The immunophenotype of MM patients’ plasma cells includes: CD138+, CD38++, CD79a+, CD27(40-50%+), CIg+, SIg-, CD56(75%++), CD117(30%+), CD20(30%+), CD10- /+, CD19–, cytoplasmic κ/λ abnormalities. Among these, CD38 and CD138 are the most definite and reliable shared phenotypes of malignant plasma cells. The combination of CD38/CD56/CD19/CD45 can identify over 90% of tumor cells and normal plasma cells. The most notable difference is that myeloma cells express light chain restriction, meaning they express either kappa or lambda light chains. To determine the malignancy of plasma cells, cytogenetic testing can be used. (1) Fluorescence in situ hybridization (FISH) testing: FISH testing should be performed after plasma cell enrichment; it should be repeated in relapsed patients; FISH has a sensitivity of 10-2 and is not recommended as a method for minimal residual disease (MRD) detection. (2) Mandatory items: -t(4;14), t(14;16); -17p deletion (P53). (3) Optional items: -13q deletion; -1q/1p; -t(11;14).
2. Finding (Screening) M Protein
For patients clinically suspected of plasma cell diseases (such as renal insufficiency, multiple lytic bone destruction, anemia, hypercalcemia, neuropathy, etc.), screening for M protein should be performed. Typically, serum free light chains, protein electrophoresis, and immunofixation electrophoresis are used to screen for monoclonal plasma cell proliferative diseases. If a diagnosis of plasma cell disease is confirmed, all patients should undergo 24-hour urine protein electrophoresis (PEL) and immunofixation electrophoresis (IFE) testing, especially in non-secretory, oligosecretory, and light-chain myeloma. The sensitivity comparison of different testing methods is shown in the figure below.
3. Finding End-Organ Damage Manifestations – Imaging
End-organ damage can be detected through imaging examinations. Specific methods include skeletal radiography, whole-body low-dose CT (WB-LDCT), MRI, PET-CT, each with its advantages, disadvantages, and applicable scope as shown in the table below.
In summary, the diagnostic steps for MM are as follows: (1) Quantification of M protein + Clonal Plasma Cells (PC): serum protein electrophoresis + IFE; 24-hour urine protein electrophoresis + IFE; immunoglobulin quantification; serum free light chain (FLC) detection; bone marrow aspiration + biopsy; peripheral blood smear, flow cytometry; (2) Examination of end-organ damage: complete blood count; biochemical renal function; blood calcium; various enzyme assays, such as lactate dehydrogenase (LDH); imaging assessment, including CT, PET-CT, MRI. The diagnostic workflow for MM is shown in the figure below.
For assessing the efficacy of MM treatment around the three elements: (1) Clonal Plasma Cells: Minimal Residual Disease (MRD) detection in bone marrow, detection methods: second-generation flow cytometry (NGF), second-generation sequencing (NGS), PET-CT, bone marrow biopsy immunohistochemistry; testing frequency: after 3-4 cycles of induction therapy, after autologous stem cell transplantation (ASCT), after consolidation therapy, maintenance therapy every 6-12 months. (2) Monoclonal Immunoglobulin (M Protein): detection methods: serum & 24-hour urine protein electrophoresis + immunofixation electrophoresis, serum FLC; testing frequency: once after 1-2 cycles of induction therapy, before and after ASCT, after consolidation therapy, maintenance therapy every 3 months. (3) End-Organ Damage Caused by Plasma Cells/M Protein: detection methods: biochemical liver and kidney function, LDH, complete blood count; evaluation of bone disease, whole-body PET-CT, MRI, CT.
Expert Profile
Dr. Yin Wu, Chief Physician
• Department of Hematology, Beijing Chaoyang Hospital, Capital Medical University
• Visiting Scholar at the German Cancer Research Center, 2014-2015
• Long-term director of the ward, rich clinical experience. Specializes in the diagnosis and treatment of multiple myeloma and other plasma cell disorders. Has published multiple SCI articles and co-authored 2 books on myeloma.
• Director of the Hematology Department, Beijing Medical Association Physician Branch
• Member of the Oncology Department, China International Health Exchange and Promotion Association
• Standing Committee Member of the Lymphoma Immunotherapy Committee, Beijing Cancer Prevention and Control Society
• Member of the Hematological Diseases Branch, China Association of Traditional Chinese Medicine
• Committee Member of the Chinese Myelodysplastic Syndrome and Myeloproliferative Neoplasm Working Group, Hematology Tumor Professional Committee, Chinese Anti-Cancer Association
• Medical Identification Expert, Beijing Medical Association
• Expert in Adverse Reactions to Vaccination, Chinese Medical Association
