-
Categories
-
Pharmaceutical Intermediates
-
Active Pharmaceutical Ingredients
-
Food Additives
- Industrial Coatings
- Agrochemicals
- Dyes and Pigments
- Surfactant
- Flavors and Fragrances
- Chemical Reagents
- Catalyst and Auxiliary
- Natural Products
- Inorganic Chemistry
-
Organic Chemistry
-
Biochemical Engineering
- Analytical Chemistry
- Cosmetic Ingredient
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
In July 2021, the European Myeloma Working Group (EMN) issued a consensus on the identification and management of smoking multiple myeloma (SMM)
.
According to the latest International Myeloma Working Group (IMWG) standards, SMM is an asymptomatic plasma cell disease characterized by elevated M protein levels> 3g/dL, bone marrow plasma cell infiltration ≥10% and <60%, and lack of Any myeloma defines the event
.
This article focuses on the new insights into the pathogenesis of SMM, proposes a new prognostic scoring system, and provides practical guidance and recommendations for patient management
.
Clinical features of SMM Compared with monoclonal globulinemia of unknown significance (MGUS), SMM has a higher tumor burden, but it does not have clinical features of end-organ damage and does not show any other myeloma-defining events
.
Among all patients with multiple myeloma (MM), 8%-14% have SMM.
The median age of onset of patients is 67 years, and the annual incidence rate is 0.
4 cases per 100,000 people.
The incidence rate is higher among African Americans.
.
The median time for SMM to progress to MM is about 5 years.
In the first 5 years after SMM is diagnosed, the incidence of MM progresses to about 10%, drops to 3% in the second 5 years, and about 1% every year thereafter
.
However, nearly one-third of SMM patients will not progress to MM
.
SMM pathogenesis All cases of MM develop through the MGUS and SMM stages, although these stages are usually not clinically obvious
.
The mechanism for the development from MGUS to SMM or MM is not yet clear
.
Studies have shown that the mechanisms that play an important role in the transformation from MGUS to SMM to MM involve chromosomal abnormalities, gene deletions, gene amplification, gene ectopics, gene mutations, and epigenetic changes
.
Analysis of the paired SMM-MM genome revealed two progress patterns: ①Evolve from tiny or completely new subclones; ②Unrelated to genome changes
.
In addition, the bone marrow microenvironment also plays an important role in the occurrence and progression of MGUS/SMM
.
SMM diagnosis and monitoring SMM is currently diagnosed according to IMWG standards (Table 1)
.
The updated IMWG criteria reclassified 10-15% of patients previously diagnosed with SMM, according to the new myeloma definition event (malignant tumor biomarker: bone marrow monoclonal plasma cell ratio>60%, free light chain ratio>100, MRI detected> 1 focal lesion), the so-called "SLIM CRAB" standard, classified as "ultra-high risk" SMM
.
These patients are considered eligible for comprehensive MM treatment, and the risk of progression after 2 years is approximately 80%
.
Table 1 IMWG's diagnostic criteria for MGUS, SMM and MM *CRAB: Serum calcium is higher than the upper limit of normal> 1 mg/dL or> 11 mg/dL; renal insufficiency: serum creatinine> 2 mg/dL or creatinine clearance rate <40 mL/min ; Anemia: hemoglobin is lower than the lower limit of normal> 2g/dL or <10g/dL; bone lesions: imaging examination (including X-ray film, CT or PET-CT) shows one or more osteolytic lesions
.
**SLiM: bone marrow monoclonal plasma cell ratio ≥60%; serum involved/unaffected free light chain ratio>100; MRI shows >1 focal bone destruction above 5mm.
Clinical and laboratory monitoring of SMM should be initially diagnosed After that, it will be done every 2-3 months for 6-12 months
.
If the test results are stable, follow up every 4-6 months for another year, and every 6-12 months thereafter
.
Of course, follow-up should be individualized based on the risk of progression
.
The members of the expert panel believe that it is best to use MRI every year for the first 5 years (because MRI is more sensitive to early damage), or when clinical suspicion/pain or M protein gradually increases (low-dose whole body CT).
Or MRI)
.
SMM prognosis stratification In the past few years, combined with routine laboratory parameters, some risk scoring systems for SMM progression have emerged, as shown in Table 2
.
Table 2 SMM prognostic stratification model PD, disease progression; TTP, time to progression; sFLC, serum free light chain; sFLCr, serum free light chain ratio; SWOG, Southwest Tumor Working Group; CMG, Czech myeloma group; GEP-70 , University of Arkansas Gene Expression Profiling*sFLCr score: <10: 0; 10-25: 2; >25-40: 3; >40: 5.
M protein score: 0-1.
5g/dL: 0; >1.
5-3g /dL: 3; >3g/dL: 4.
Proportional integral of bone marrow monoclonal plasma cells: 0-15%: 0; >15%-20%: 2; >20%-30%: 3; >30%-40 %: 5; >40%: 6
.
**The traditional treatment of SMM in the verification cohort is follow-up observation.
With the development of MM treatment drugs, while weighing the side effects and efficacy of drugs, many researchers have begun to try to explore and carry out early treatment of SMM in order to control the disease , Delay the time of disease progression
.
Several randomized controlled studies have compared the effects of early treatment and delayed treatment of SMM on the prognosis of the disease.
The study drugs include daratumomab, melphalan + prednisone, bisphosphonates ± thalidomide, and cetuximab , lenalidomide + dexamethasone
.
In general, early treatment significantly reduces the progression of SMM, but the risk of secondary malignancies significantly increases after early treatment
.
The treatments used in most trials are widely heterogeneous and lack risk stratification
.
The guidelines summarized recent clinical studies on the treatment of SMM, as shown in Table 3
.
Table 3 Summary of SMM treatment related clinical trials ORR, objective response rate; CR, complete response; MRD, minimal residual disease; PFS, progression-free survival; TTP, time to progression; OS, overall survival; IRD, ixazomib +lenalidomide + dexamethasone; MFC, multi-parameter flow cytometry; NGS, next-generation sequencing; NA, not applicable; NR, not reached; PD/DR, disease progression/death ratio despite many ongoing and The planned study, but whether intensive treatment with new drugs will also have a broad impact on the overall survival of SMM patients is still inconclusive
.
The key issue remains to identify those high-risk SMM patients who "must" receive treatment
.
Recommendations for improving SMM management in the future According to current standards, active observation is recommended for low-risk SMM patients
.
There is no consensus on the early treatment of high-risk SMM
.
Clinically, patients with multiple risk factors should be considered, especially those with increased M protein level or bone marrow monoclonal plasma cell count or significantly decreased hemoglobin concentration, high FLC ratio and/or high risk of cytogenetics, which will further increase the disease progression For these cases, consider starting treatment or participating in clinical trials
.
Due to the substantial differences between different studies (such as the definition of high-risk group SMM, the intensity of treatment methods, and the criteria/methods for evaluating response and progress), it is difficult to compare the treatment results currently evaluated in SMM
.
Therefore, before clearly changing the current SMM management model, comparable large-sample clinical trials must be conducted to solve the following problems: ① Identify new predictive biomarkers (clinical, molecular/genomics, immunology, microenvironment, Imaging) to further improve the risk stratification
.
②Assess the necessary balance between early treatment to reduce the risk of disease progression (and subsequent MM) and possible short-term and long-term adverse effects (especially deterioration of quality of life, secondary malignancies)
.
③Determine which intensity and type of treatment is advisable in the selected high-risk SMM patients, that is, short-term, intensive "curative" treatment or long-term immune control of the disease.
Both methods should be used The main goal is to improve the overall survival rate without affecting the patient's quality of life
.
References: 1.
Musto P, et al.
2021 European Myeloma Network review and consensus statement on smoldering multiple myeloma: how to distinguish (and manage) Dr.
Jekyll and Mr.
Hyde.
Haematologica.
2021 Jul 15.
doi: 10.
3324/haematol .
2021.
278519.
Stamp "read the original text", we make progress together
.
According to the latest International Myeloma Working Group (IMWG) standards, SMM is an asymptomatic plasma cell disease characterized by elevated M protein levels> 3g/dL, bone marrow plasma cell infiltration ≥10% and <60%, and lack of Any myeloma defines the event
.
This article focuses on the new insights into the pathogenesis of SMM, proposes a new prognostic scoring system, and provides practical guidance and recommendations for patient management
.
Clinical features of SMM Compared with monoclonal globulinemia of unknown significance (MGUS), SMM has a higher tumor burden, but it does not have clinical features of end-organ damage and does not show any other myeloma-defining events
.
Among all patients with multiple myeloma (MM), 8%-14% have SMM.
The median age of onset of patients is 67 years, and the annual incidence rate is 0.
4 cases per 100,000 people.
The incidence rate is higher among African Americans.
.
The median time for SMM to progress to MM is about 5 years.
In the first 5 years after SMM is diagnosed, the incidence of MM progresses to about 10%, drops to 3% in the second 5 years, and about 1% every year thereafter
.
However, nearly one-third of SMM patients will not progress to MM
.
SMM pathogenesis All cases of MM develop through the MGUS and SMM stages, although these stages are usually not clinically obvious
.
The mechanism for the development from MGUS to SMM or MM is not yet clear
.
Studies have shown that the mechanisms that play an important role in the transformation from MGUS to SMM to MM involve chromosomal abnormalities, gene deletions, gene amplification, gene ectopics, gene mutations, and epigenetic changes
.
Analysis of the paired SMM-MM genome revealed two progress patterns: ①Evolve from tiny or completely new subclones; ②Unrelated to genome changes
.
In addition, the bone marrow microenvironment also plays an important role in the occurrence and progression of MGUS/SMM
.
SMM diagnosis and monitoring SMM is currently diagnosed according to IMWG standards (Table 1)
.
The updated IMWG criteria reclassified 10-15% of patients previously diagnosed with SMM, according to the new myeloma definition event (malignant tumor biomarker: bone marrow monoclonal plasma cell ratio>60%, free light chain ratio>100, MRI detected> 1 focal lesion), the so-called "SLIM CRAB" standard, classified as "ultra-high risk" SMM
.
These patients are considered eligible for comprehensive MM treatment, and the risk of progression after 2 years is approximately 80%
.
Table 1 IMWG's diagnostic criteria for MGUS, SMM and MM *CRAB: Serum calcium is higher than the upper limit of normal> 1 mg/dL or> 11 mg/dL; renal insufficiency: serum creatinine> 2 mg/dL or creatinine clearance rate <40 mL/min ; Anemia: hemoglobin is lower than the lower limit of normal> 2g/dL or <10g/dL; bone lesions: imaging examination (including X-ray film, CT or PET-CT) shows one or more osteolytic lesions
.
**SLiM: bone marrow monoclonal plasma cell ratio ≥60%; serum involved/unaffected free light chain ratio>100; MRI shows >1 focal bone destruction above 5mm.
Clinical and laboratory monitoring of SMM should be initially diagnosed After that, it will be done every 2-3 months for 6-12 months
.
If the test results are stable, follow up every 4-6 months for another year, and every 6-12 months thereafter
.
Of course, follow-up should be individualized based on the risk of progression
.
The members of the expert panel believe that it is best to use MRI every year for the first 5 years (because MRI is more sensitive to early damage), or when clinical suspicion/pain or M protein gradually increases (low-dose whole body CT).
Or MRI)
.
SMM prognosis stratification In the past few years, combined with routine laboratory parameters, some risk scoring systems for SMM progression have emerged, as shown in Table 2
.
Table 2 SMM prognostic stratification model PD, disease progression; TTP, time to progression; sFLC, serum free light chain; sFLCr, serum free light chain ratio; SWOG, Southwest Tumor Working Group; CMG, Czech myeloma group; GEP-70 , University of Arkansas Gene Expression Profiling*sFLCr score: <10: 0; 10-25: 2; >25-40: 3; >40: 5.
M protein score: 0-1.
5g/dL: 0; >1.
5-3g /dL: 3; >3g/dL: 4.
Proportional integral of bone marrow monoclonal plasma cells: 0-15%: 0; >15%-20%: 2; >20%-30%: 3; >30%-40 %: 5; >40%: 6
.
**The traditional treatment of SMM in the verification cohort is follow-up observation.
With the development of MM treatment drugs, while weighing the side effects and efficacy of drugs, many researchers have begun to try to explore and carry out early treatment of SMM in order to control the disease , Delay the time of disease progression
.
Several randomized controlled studies have compared the effects of early treatment and delayed treatment of SMM on the prognosis of the disease.
The study drugs include daratumomab, melphalan + prednisone, bisphosphonates ± thalidomide, and cetuximab , lenalidomide + dexamethasone
.
In general, early treatment significantly reduces the progression of SMM, but the risk of secondary malignancies significantly increases after early treatment
.
The treatments used in most trials are widely heterogeneous and lack risk stratification
.
The guidelines summarized recent clinical studies on the treatment of SMM, as shown in Table 3
.
Table 3 Summary of SMM treatment related clinical trials ORR, objective response rate; CR, complete response; MRD, minimal residual disease; PFS, progression-free survival; TTP, time to progression; OS, overall survival; IRD, ixazomib +lenalidomide + dexamethasone; MFC, multi-parameter flow cytometry; NGS, next-generation sequencing; NA, not applicable; NR, not reached; PD/DR, disease progression/death ratio despite many ongoing and The planned study, but whether intensive treatment with new drugs will also have a broad impact on the overall survival of SMM patients is still inconclusive
.
The key issue remains to identify those high-risk SMM patients who "must" receive treatment
.
Recommendations for improving SMM management in the future According to current standards, active observation is recommended for low-risk SMM patients
.
There is no consensus on the early treatment of high-risk SMM
.
Clinically, patients with multiple risk factors should be considered, especially those with increased M protein level or bone marrow monoclonal plasma cell count or significantly decreased hemoglobin concentration, high FLC ratio and/or high risk of cytogenetics, which will further increase the disease progression For these cases, consider starting treatment or participating in clinical trials
.
Due to the substantial differences between different studies (such as the definition of high-risk group SMM, the intensity of treatment methods, and the criteria/methods for evaluating response and progress), it is difficult to compare the treatment results currently evaluated in SMM
.
Therefore, before clearly changing the current SMM management model, comparable large-sample clinical trials must be conducted to solve the following problems: ① Identify new predictive biomarkers (clinical, molecular/genomics, immunology, microenvironment, Imaging) to further improve the risk stratification
.
②Assess the necessary balance between early treatment to reduce the risk of disease progression (and subsequent MM) and possible short-term and long-term adverse effects (especially deterioration of quality of life, secondary malignancies)
.
③Determine which intensity and type of treatment is advisable in the selected high-risk SMM patients, that is, short-term, intensive "curative" treatment or long-term immune control of the disease.
Both methods should be used The main goal is to improve the overall survival rate without affecting the patient's quality of life
.
References: 1.
Musto P, et al.
2021 European Myeloma Network review and consensus statement on smoldering multiple myeloma: how to distinguish (and manage) Dr.
Jekyll and Mr.
Hyde.
Haematologica.
2021 Jul 15.
doi: 10.
3324/haematol .
2021.
278519.
Stamp "read the original text", we make progress together
