How is the efficacy of multiple myeloma evaluated and monitored (1)?

  Multiple myeloma (MM ) is a malignant clonal plasma cell disease in which the tumor itself or the immunoglobulins it produces can cause functional impairment of multiple organs, causing a range of symptoms such as bone pain or fractures, kidney damage, infections, anemia and hypercalcemia. Although the introduction of new drugs such as immunomodulators (IMiDs) thalidomide and ranadomide and the proteasome inhibitor bortezomib (BZ) has been effective in the last decade, and the disease-free survival of patients has been significantly prolonged, most patients will eventually relapse after a short remission, and the goal of treatment is to obtain and maintain complete remission in the majority of patients. In view of this, it is important to assess and monitor the efficacy in the course of multiple myeloid therapy.  (For patients with clinically suspected MM, the necessary tests should be completed. 1. routine blood tests, including leukocyte classification and peripheral blood smear; 2. blood biochemical tests, including serum calcium, creatinine, β2-microglobulin and lactate dehydrogenase; 3. serum protein electrophoresis; 4. 24-hour urine protein analysis and electrophoresis; 5. blood immunoglobulin quantification; 6. serum and urine immunofixation electrophoresis  7. serum free light chain assay; 8. skeletal radiographs including spine, pelvis and skull; 9. bone marrow smear/biopsy morphological analysis, immunological analysis; 10. bone marrow plasma cell cytogenetic analysis including karyotyping and FISH analysis); 11. CT scan and/or MR if clinically indicated; 12. PET/CT examination, mainly for extramedullary plasma cell tumors. It is important to note: collection of baseline values for multiple indicators such as serum and/or urine M-protein, presence of plasma cell infiltration, serum free light chain (FLC), presence of extramedullary plasmacytoma, presence of end organ damage, disease risk stratification, and presence of contraindications to drug use. Serum and urine total protein levels and their electrophoresis can determine the presence of M protein peaks and patterns, while fixed electrophoresis reveals the specific light and heavy chains that make up the monoclonal group. Careful analysis of peripheral blood coating is required to exclude plasma cell leukemia (plasma cells in peripheral blood more than 20% or absolute number greater than 2×09/L).  (B) Diagnostic criteria According to the 2003 International Myeloma Working Group (IMWG), 2008 WHO, 2013 National Comprehensive Cancer Network (NCCN) and the latest definition of MM, the criteria for diagnosing symptomatic myeloma and asymptomatic myeloma (smoldering myeloma) are as follows.  1. Diagnostic criteria for symptomatic myeloma (meeting all 3 criteria): (1) bone marrow monoclonal plasma cell percentage ≥ 10%a and/or tissue biopsy demonstrating plasmacytoma; (2) presence of monoclonal M protein in serum and/or urineb .  (3) Myeloma-related target organ damage (at least one or more): corrected serum calcium c > 2, 65 mmol/L, renal impairment (creatinine > 177 μmol/L), anemia (hemoglobin below the lower limit of normal 20 g/L or < 100 g/L), osteolytic destruction, severe osteoporosis or pathological fractured, and other types of end-organ damage occasionally; if, after treatment, confirmation of damage to these organs in association with myeloma may further support the diagnosis.  a In rare cases, the proportion of bone marrow monoclonal plasma cells <10%, but it can be confirmed that CRAB symptoms are caused by clonal plasma cells, which can also be diagnosed; b Without the limitation of blood or urine M protein amount, if no M protein is detected (diagnosis of non-secretory MM), then myeloma monoclonal plasma cells ≥30% or biopsy of plasmacytoma and confirmation of κ or λ light chain restricted expression such as immunohistochemistry is required; c Corrected serum calcium (mmol/L) = serum calcium measurement (mmol/L) + [4-serum albumin concentration (g/dl)] × 0,02 or corrected serum calcium (mg/dl) = serum calcium measurement (mg/dl) + [4-serum albumin concentration (g/dl)] × 0,8; d If isolated plasmacytoma (confirmed by biopsy) or simple diffuse osteoporosis (no fracture) is used as separate diagnostic criteria, the proportion of bone marrow monoclonal plasma cells ≥ 30% is required.  2. Diagnostic criteria for asymptomatic myeloma (smoldering myeloma): (1) serum monoclonal M protein ≥ 30 g/L, and/or; (2) bone marrow monoclonal plasma cell ratio ≥ 10%; (3) no associated organ and tissue damage (no end-organ damage, including osteolytic changes).  (C) Typing According to the increased abnormal immunoglobulin heavy chain type can be divided into IgG type, IgA type, IgD type, IgM type, IgE type, light chain type, biclonal type, and non-secretory type. Each of these can be further divided into κ and λ types according to the light chain type, for a total of 14 types.