scholarly journals Prediction of Progression of Smouldering into Therapy Requiring Multiple Myeloma By Easily Accessible Clinical Factors [in 527 Patients]

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2071-2071 ◽  
Author(s):  
Roman Hajek ◽  
Viera Sandecka ◽  
Anja Seckinger ◽  
Ivan Spicka ◽  
Vlastimil Scudla ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Plasma Cells ◽  
Risk Model ◽  
Validation Cohort ◽  
M Protein ◽  
Tumour Mass ◽  
Clinical Parameters ◽  
Clinical Factors ◽  
Risk Of Progression

Abstract Background Several models predict the progression from smouldering multiple myeloma (SMM) to therapy requiring multiple myeloma (MM). Three models comprise the assessment of tumour mass by different clinical parameters to stratify in risk groups: 1) the Mayo Clinic model uses bone marrow plasma cells percentage (BMPC) and serum monoclonal protein (M-protein), 2) the PETHEMA model uses immunoparesis and the percentage of abnormal plasma cells by flow cytometry, 3) the Heidelberg group assesses tumour mass by either the percentage of malignant plasma using iFISH or the Mayo assessment depicted above, and the presence of chromosomal aberrations associated with adverse prognosis. Besides tumor mass, they find the number of focal lesions in whole body MRI (>1) as strong prognostic factor. Aim To assess a combination of easily accessible clinical factors identifying patients at ≥ 80% risk of progression to MM requiring treatment within two years from the diagnosis of SMM. Methods Data for this study were obtained from the Registry of Monoclonal Gammopathies (RMG) acquired from hematologic centers of the Czech Republic for 287 SMM patients enrolled from May 2007 to June 2013. A cohort comprising 240 SMM patients from Heidelberg, Germany was used for validation (Neben et al. JCO 2013). Results During the follow up period (median 2.4 years; range 0.6 - 18.0) progression to MM was observed in 51.9% (149/287) patients in the study cohort, representing 16% risk of progression at 1 year, 31.2% at 2 years, 54.8% at 5 years and 73.4% at 10 years. In univariate analysis factors significantly associated with progression were as follows: serum free light chain (iFLC/uFLC) ratio > 30 (HR 2.4 [95% CI: 1.4 - 4.1]; p< 0.001) plasma cell infiltration in bone marrow cytology ≥ 15% (HR 2.1 [1.5-3.0]; p< 0.001), immunoparesis (HR 2.0 [1.3-2.9]; p< 0.001), M - protein concentration ≥ 2.3 g/dL (HR 2.00 [1.4-2.7]; p< 0.001), beta2 microglobulin ≥ 2.0 mg/l (HR 1.8 [1.2-2.7]; p= 0.001), and thrombocyte count ≤ 250 x 109/l (HR 1.7 [1.1-2.4]; p= 0.005). In multivariate analysis, 3 parameters showed independent predictive value (immunoparesis, serum M-protein quantity ≥ 2.3 g/dL and iFLC/uFLC > 30). Combining these factors, we proposed a new risk model for SMM patients (CMG model). The risk of progression from SMM to MM at 2 years was 18.5%, 20.9%, 41.9% and 78.7% if 0 (reference group), 1, 2 or 3 risk factors are present (p< 0.001) (Figure 1) with HR of 1.5 [0.7-2.9]; p=0.283, 2.5 [1.3-5.0]; p= 0.008, 6.8 [3.0-15.2]; p<0.001, n=139), respectively. The CMG model was validated on 240 SMM patients from Heidelberg published in 2013. The risk of progression from SMM to MM at 2 years was 5.3%, 7.5%, 44.8% and 81.3% if 0, 1, 2 or 3 risk factors were present, respectively (p< 0.001) (Figure 1) with HR of 4.2 ([0.5-36.1]; p=0.189), 21.5 ([2.9-159.1]; p= 0.003, HR 38.6 [4.7- 317.7]; p<0.001, n=113). Conclusion We propose and validate a new risk model for SMM patients with prediction of 80% (78.7% on our CMG model; 81.3% on data from Heidelberg) risk of progression to therapy requiring myeloma within two years based on easily accessible clinical parameters (CMG model). The model could especially be used to identify high-risk patients to be included in early treatment clinical trials. Acknowledgments: This work was supported by grants NT13492-4, NT14575-3 and by EU FP7/2007-2013; grant n°278570 and “OverMyR”, as well as the Deutsche Forschungs-Gemeinschaft (DFG) SFB/TRR79. Figure 1: CMG risk model: CMG cohort of patients and validation cohort of Heidelberg patients Figure 1:. CMG risk model: CMG cohort of patients and validation cohort of Heidelberg patients Disclosures Seckinger: Novartis: Research Funding.

Metastatic Bone Survey in Monoclonal Gammopathy of Undertermined Significance: Useful or Not?

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2728-2728
Author(s):  
Vrushali s Dabak ◽  
Esther Urbaez Duran ◽  
Muath Dawod ◽  
Amr Hanbali
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Serum Calcium ◽  
Plasma Cells ◽  
Bone Marrow Aspiration ◽  
Hemoglobin Concentration ◽  
M Protein ◽  
Risk Of Progression ◽  
Male Sex

Abstract Introduction: Monoclonal gammopathy of undetermined significance (MGUS) is defined as the presence of a serum monoclonal protein &lt;3g/dl, with fewer than 10% plasma cells in bone marrow and absence of lytic bone lesions, anemia, hypercalcemia and renal insufficiency. Incidence increases with age, especially over 70 and its progression to malignant disease occurs at 1% per year. However, so far there are no studies which can reliably distinguish patients who would progress from those who would remain stable. Based on available literature, it is concluded that MGUS has low risk of progression when M-protein is less than 1.5 g/dl, with no reduction in polyclonal immunoglobulins and bone marrow plasma cells less than 5%. The recommended testing with suspected MGUS is hemoglobin concentration, protein studies, serum calcium, and creatinine. Metastatic bone survey (MBS) and bone marrow aspiration are felt unnecessary if M-protein is less than 1.5 g/dl. However literature to support the use of MBS at diagnosis based on the level of M-protein is limited. Also our observation has been that due to lack of clear guidelines, most physicians obtain a baseline MBS and some follow patients with yearly or every other year MBS irrespective of the level of M-protein. Hence, we decided to review patients diagnosed with MGUS at our institution to determine the importance of MBS and if possible identify risk factors like age, race, M-protein level, hemoglobin concentration, serum calcium or creatinine level, which would identify a subgroup of patients needing a MBS. In doing so we were hoping to separate out those patients in whom we could recommend against unnecessary use of the skeletal survey below a certain defined M protein level. Study: We reviewed charts on 1906 patients at Henry Ford hospital diagnosed with MGUS between 1990 and 2007. All patients with at least one M-protein and one MBS done were included in the analysis. We excluded patients with a level of M-protein &gt;3.0 g/dl, who never had a skeletal survey in our system, had a light chain myeloma, plasmacytoma, chronic lymphocytic lymphoma(CLL), amyloidosis or protein evaluation done for diagnosis other than MGUS. We had 620 such patients. We collected data regarding their age, sex, ethnicity, date of diagnosis, type and level of the M-protein, hemoglobin level, serum calcium and creatinine at baseline, result of the MBS, date of progression to multiple myeloma (MM) if any and the date of last follow up if they did not progress to MM. Positive MBS is defined as x ray findings consistent with myelomatous changes with bone marrow aspiration confirming diagnosis of MM. Results: Of 620 patients, 36 had a positive MBS and applying non parametric Mann Whitney test and a chi-squared test, positive results seemed to correlate with higher level of M-protein, IgG subtype, lower hemoglobin and higher creatinine. Male sex and older age were other risk factors. Using the LOES curve to graph the risk of a positive skeletal event with the level of M-protein, risk was noted to increase significantly with M-protein in the range of 1.8– 3.0 (odds ratio 8.84 compared with 1.31 if level was less than 1.8), which was highly statistically significant as shown in figure 1. Further for 97/620 who progressed to multiple myeloma, the risk of progression was significantly higher for males, younger age at diagnosis of MGUS, lower hemoglobin, higher level of M-protein, IgG subtype and a positive skeletal event. Discussion: Our study is a retrospective chart review with its own limitations. However to our knowledge this is the first study to define the level of M-protein in patients with MGUS above which obtaining a MBS may be of value. Our study identifies 1.8 as a cut off value of M-protein below which doing routine MBS without symptoms of bone pains or other laboratory features suggesting progression to multiple myeloma might be unnecessary. Other risk factors for a positive event and progression to MM like lower hemoglobin, higher creatinine, older age, male sex and IgG subtype in our study are in keeping with what has been described in the literature. Conclusion: Based on our study, obtaining baseline MBS in all patients with suspected MGUS was not beneficial. Hence, we would not recommend obtaining MBS in patients with M-protein &lt;1.8 g/dl in absence of other risk factors for progression to multiple myeloma. Figure 1: LOES curve showing increased likelihood of positive MBS for increasing MPEV level. Figure 1:. LOES curve showing increased likelihood of positive MBS for increasing MPEV level.

scholarly journals Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myeloma

Blood ◽  
2008 ◽  
Vol 111 (2) ◽  
pp. 785-789 ◽  
Author(s):  
Angela Dispenzieri ◽  
Robert A. Kyle ◽  
Jerry A. Katzmann ◽  
Terry M. Therneau ◽  
Dirk Larson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Plasma Cells ◽  
Risk Model ◽  
Free Light Chain ◽  
M Protein ◽  
Serum Samples ◽  
Baseline Serum ◽  
Increased Risk ◽  
Risk Of Progression

We hypothesized that increased monoclonal free kappa or lambda immunoglobulin light chains in smoldering multiple myeloma (SMM), as detected by the serum free light chain (FLC) assay, indicates an increased risk of progression to active myeloma. Baseline serum samples obtained within 30 days of diagnosis were available in 273 patients with SMM seen from 1970 to 1995. At a median follow-up of surviving patients of 12.4 years, transformation to active disease has occurred in 59%. The best breakpoint for predicting risk of progression was an FLC ratio of 0.125 or less, or 8 or more (hazard ratio, 2.3; 95% CI, 1.6-3.2). The extent of abnormality of FLC ratio was independent of SMM risk categories defined by number of bone marrow plasma cells (BMPCs) and size of serum M proteins (BMPC ≥ 10% and serum M protein ≥ 3 g/dL; BMPC ≥ 10% but serum M protein < 3 g/dL; and serum M protein≥ 3 g/dL but BMPC < 10%). Incorporating the FLC ratio into the risk model, the 5-year progression rates in high-, intermediate-, and low-risk groups were 76%, 51%, and 25%, respectively. The serum immunoglobulin FLC ratio is an important additional determinant of clinical outcome in patients with SMM.

Immunoglobulin Free Light Chains at Diagnosis: Predictors of Progression and Survival in Solitary Plasmacytoma of Bone.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5080-5080 ◽  
Author(s):  
David Dingli ◽  
Robert A. Kyle ◽  
Vincent S. Rajkumar ◽  
Grzegorz S. Nowakowski ◽  
Dirk R. Larson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Univariate Analysis ◽  
Prognostic Indicator ◽  
M Protein ◽  
Solitary Plasmacytoma ◽  
Time To Progression ◽  
Number Of Patients ◽  
M Proteins ◽  
Risk Of Progression

Abstract Background: Solitary plasmacytoma of bone (SBP) is a localized collection of monoclonal plasma cells that is potentially curable with local radiation therapy but associated with a high risk of progression to multiple myeloma. We hypothesized that an abnormal immunoglobulin free light (FLC) ratio at diagnosis may be a prognostic indicator of transformation risk. Methods: We identified a cohort of 133 patients with SBP for whom stored serum taken at the time of diagnosis was available. The diagnosis was ascertained and serum FLC determined in 126 patients. Results: From this cohort, 48 patients have progressed to myeloma and the median time to progression among those who progressed was 1.9 years. On univariate analysis, age (p&lt;0.001), gender (p=0.035), abnormal FLC ratio at diagnosis (p=0.009) and persistence of serum or urine M-protein after therapy (p=0.0070 were all associated with a shorter overall survival (OS) and time to progression to multiple myeloma. Progression by Normal FLC(0.26–1.65) Progression by Normal FLC(0.26–1.65) On multivariate analysis, an abnormal FLC ratio retained its independence in a model that includes age at diagnosis but lost its significance when combined with persistence of the serum or urine M-protein. However, serum or urine M-proteins are not detectable in a significant number of patients with SBP and therefore not informative. Conclusion: The FLC ratio at the time of diagnosis of SBP is a powerful predictor of risk and a useful aid to management of patients with this condition.

scholarly journals Short-Term Risk of Progression of Patients with Asymptomatic Monoclonal Gammopathies to Active Multiple Myeloma: The Critical Impact of the Tumoral Mass

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1795-1795
Author(s):  
Anna Benedetta Dalla Palma ◽  
Laura Notarfranchi ◽  
Jessica Crosara ◽  
Mario Pedrazzoni ◽  
Fabrizio Accardi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Risk Score ◽  
Statistical Significance ◽  
Prognostic Score ◽  
Univariate Analysis ◽  
M Protein ◽  
Short Term ◽  
Risk Of Progression ◽  
Risk Patients

The identification of risk factors for progression is critical in the clinical management and appropriate follow up of patients with pre-malignant Asymptomatic Monoclonal Gammopathies (AMG) including Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM). The development of prognostic score and consequently the early identification of patients with possible short-term progression to Multiple Myeloma (MM) could lead to anticipate the treatment. In this study, we retrospectively evaluated possible risk factors of short-term progression to active MM in a large cohort of MGUS and SMM patients admitted to a single haematological center (Hematology and BMT Unit, University Hospital of Parma) between 2010 and 2018. We analysed a total cohort of 235 patients diagnosed with AMG (81 MGUS and 154 SMM) according to the IMWG recently updated diagnostic criteria. All patients analysed underwent to Bone Marrow (BM) examination; moreover, imaging evaluation was performed in 22 MGUS and 123 SMM patients, in order to exclude the presence of bone disease. In a subgroup of AMG patients (n=50), bone mineral density (BMD) evaluation by Dual-energy X-ray Absorptiometry (DXA) was also available. Median age of the AMG patients analysed was 68 years (range 35-93 years). Median percentage of BM plasma cells (BMPCs) was 12% (range 2-55%) in the entire population, 7% (range 2-9) in MGUS and 15% (range 10-55) in SMM patients. Median serum M-protein was 1.7 g/dL (range: 0.17-4.5), 1.5 g/dL (range 0.17-4.5) in MGUS and 1.8 g/dL (range 0.4-2.7) in SMM patients. An abnormal free light chain (FLC) ratio was found in 70% of AMG patients, among the ones that performed the analysis; regarding SMM patients, FLC ratio value was available in 97 patients: in 72 (76%) the ratio was unbalanced, 37 (39%) had a FLC ratio ≤ 0.125 or ≥ 8 and in 14 (15%) it was > 20; among MGUS patients, value was collected in 41 patients and in 21 (51%) it was <0.26 or >1.65. The presence of immunoparesis in one or two uninvolved immunoglobulins occurred in 59% of the entire population. The median follow up time was 18 months (range 0 - 111 months) for whole population. Overall 44 patients of the entire cohort progressed to MM (41 SMM and 3 MGUS) with a median TTP of 14.5 months. By univariate analysis we found that percentage of BMPCs, entity of M-protein and presence of immunoparesis were significantly correlated with progression to active MM (p<0.001 for each variable). On the other hand, abnormal FLC ratio did not reach a statistical significance, as well as value of the involved FLC (p=0.059). Nevertheless, the presence of a FLC ratio < 0.125 or > 8 (as used in Mayo scoring system for SMM) showed a relationship at the limit of statistical significance in this subgroup of patients (p=0.052). Any significant correlation was not observed with age, sex, Ig isotype, light chain's type and the BMD values (p=NS). Afterwards, we applied Kaplan Meier method on risk factors resulted significant in univariate analysis demonstrating that they also significantly influenced the time to progression to MM. Finally, through a binomial logistic regression, we developed a new prognostic score for whole population. By combining the values of M-protein (< 2, score=0 or ≥ 2 g/dL, score=1) and the percentage of BMPC (<10%, score=0, 10-20%, score=1 and >20%, score=2), we obtained six groups at different probability of progression to active MM (Table 1). Given that result, we stratified patients in 3 groups: low-risk (score=0), intermediate-risk (score=1) and high-risk (score≥2); log-rank test confirmed that high-risk patients had a significantly shorter time to progression to symptomatic MM as compared to intermediate and low-risk patients (p<0.001). In conclusion, our results show that in patients with AMG the clinical factors, which mostly impact on the short-term risk of progression to active MM, are the entity of the PCs infiltrate and the MC related to the tumoral mass. The development of a clinical score based on BMPCs and M-protein will permit to overcome the traditional distinction between MGUS and SMM in the evaluation of the progression of AMG patients to active MM. Disclosures Giuliani: Janssen: Research Funding.

scholarly journals Evaluation of Current Clinical Models for Risk of Progression from Monoclonal Gammopathy of Undetermined Significance to Multiple Myeloma or Related Malignancies in 2028 Persons Followed in the Czech Republic

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3376-3376 ◽  
Author(s):  
Viera Sandecka ◽  
Zdenek Adam ◽  
Ivan Spicka ◽  
Vlastimil Scudla ◽  
Evzen Gregora ◽  
...  
Keyword(s):  
Risk Factors ◽  
Mayo Clinic ◽  
Plasma Cells ◽  
Reference Group ◽  
Low Risk ◽  
M Protein ◽  
The Czech Republic ◽  
Risk Of Progression ◽  
Clinical Models

Abstract Introduction: Monoclonal gammopathy of undetermined significance (MGUS) is a non-malignant condition associated with a risk of progression to multiple myeloma (MM) or related disorders. There are currently 2 clinical models predicting progression from MGUS to MM. The Mayo Clinic model uses levels and type of serum monoclonal protein (M-protein) and serum free light chain ratio (sFLC). The Spanish PETHEMA model uses flow cytometry of bone marrow plasmocytes (BMPC) and the presence of DNA aneuploidy. Purpose: The primary end point was to estimate the cumulative risk of hematologic disorders occurring during the follow-up of our cohort. The secondary end points were: to validate known clinical models suggested by the Mayo Clinic group and the Spanish PETHEMA group for the risk of progression from MGUS to MM or related malignancies and to establish a new risk model by the Czech Myeloma Group (CMG model) with better prediction of low-risk MGUS group. Group: Data for this study were obtained from the Registry of Monoclonal Gammopathies (RMG) acquired from hematologic centers of the Czech Republic. MGUS diagnosis was made according to IMWG criteria. In total, 2028 persons with MGUS were enrolled in the RMG study from May 2007 to June 2013. A total of 93% (1887/2028) of persons were evaluated. Results: 1887 MGUS persons were followed with median 4 years. Malignancies developed in 8.6% (162/1887) cases; MM occurred in 77.2% (125/162) of persons. The risk of progression was 1.5% at 1 year, 7.6% at 5 years and 16.5% at 10 years after diagnosis. The key predictors factors of progression were as follows: age ≥ 69 years, serum M- protein concentration ≥ 1.5 g/dL, BMPC > 5%, pathological sFLC ratio (< 0.26 or >1.65), immunoparesis of polyclonal immunoglobulins, levels of serum hemoglobin at baseline < 12.0 g/dL and the presence of normal plasma cells (nPC) in bone marrow ≤ 5 % identified by multiparametric flow cytometry techniques. Distribution of MGUS persons according to risk groups based on the Mayo Clinic model confirmed predictive power of Mayo Clinic model based on our data although isotype of M- protein was not found as independent predictor. At 10 years, no-risk group had 4.9% risk of progression compared to 16.3%, 24.6%, and 54.9% in groups with 1, 2 or 3 risk factors, respectively (p< 0.001). MGUS group with 1, 2 and 3 risk factors in comparison to the reference group without any risk factor had HR( 2.59 [95% CI: 1.39- 4.84]; p= 0.003, HR 4.79 [95% CI: 2.56-8.93]; p< 0.001, HR 12.97 [95% CI: 5.52-30.48];p< 0.001), retrospectively. Immunoparesis instead of DNA aneuploidy was used together with the presence of abnormal plasma cells (aPCs) to validate the modified PETHEMA model. The rates of progression at 3 years were 2.5%, 8.1% and 28.0% for groups with neither, one or both risk factors, respectively (p< 0.001). MGUS group with 1 and 2 risk factors in comparison to the reference group without any risk factor had HR (3.98 [95% CI: 1.60-9.91]; p= 0.003, HR 14.23 [95% CI: 2.86-70.76]; p< 0.001), retrospectively. Based on the 5 parameters with independent predictive value in the univariate analysis (immunoparesis, serum M-protein quantity ≥ 1.5 g/dL, BMPC > 5%, abnormal sFLC ratio and serum level of hemoglobin < 12.0 g/dL) we proposed a new CMG model. The created CMG model clearly detected MGUS persons at low risk 86.6% (828/956) with the risk of progression 5.6% at 5 years better than previously described models. As expected, the number of MGUS persons with the highest risk of progression was limited to 3.7% only (35/956), with the risk of progression 31.9% at 5 years. The MGUS group with 5 risk factors had 63 times higher hazard of progression compared to reference MGUS group (HR 63.17 [95% CI: 13.99-285.36]; p< 0.001). Conclusion: In the large cohort of MGUS persons, we confirmed validity of previously considered clinical models for the risk of progression from MGUS to MM by the Mayo Clinic group and the Spanish PETHEMA group (model used for SMM). New CMG model for the risk of progression from MGUS to MM or related malignancies was established with an advantage for better identification of MGUS persons at low risk (87% of persons with risk of progression below 10% in 5 years) as well as few persons at the highest risk of progression. As a consequence, limited evaluation and visits can be planned in majority of MGUS persons in follow-up. Acknowledgments: This work was supported by grants NT13492-4, NT14575-3 and by EU FP7/2007-2013; grant n° 278570. Disclosures No relevant conflicts of interest to declare.

scholarly journals Smoldering Multiple Myeloma: Usefulness of Serum Heavy/Light Chain Measurements for the Evaluation of Evolving Pattern

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4514-4514
Author(s):  
Carlos Fernandez de Larrea ◽  
Ignacio Isola ◽  
Esther Moga ◽  
Maria Teresa Cibeira ◽  
Ester Lozano ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Prognostic Factors ◽  
Light Chain ◽  
Protein Level ◽  
Progressive Increase ◽  
M Protein ◽  
Smoldering Multiple Myeloma ◽  
Risk Of Progression

Abstract Introduction: Smoldering multiple myeloma (SMM) is an asymptomatic and biologically heterogeneous clonal plasma cell disorder. A number of prognostic factors to identify patients at a higher risk of progression have been described, such as the size of the M protein, proportion of abnormal bone marrow plasma cells (BMPCs), immunoparesis and serum free light chain (FLC) k/l ratio. More recently, isotype-specific uninvolved heavy and light chain (HLC) pair suppression measured with the Hevylite assay was also associated with an increased risk of progression. Recent studies have evaluated the key prognostic impact of an increase in M-protein levels during follow-up ("evolving" pattern). However, an important limitation could be the evaluation of M-protein level variations based on serum protein electrophoresis (SPE) in patients with a small size M-spike. The aim of this study was to prospectively analyze the changes in M-protein according to SPE and HLC measurements, as well as other risk factors for progression, in patients with SMM. Methods: Thirty patients newly diagnosed with SMM at a single institution from January 2014 through September 2017 were prospectively included in the study. For each patient, baseline levels of known prognostic factors (serum M-protein, serum and urine immunofixation, clonal BMPCs percentage, total immunoglobulins, involved/uninvolved FLC and involved/uninvolved HLC pairs) were recorded. During the follow up, M-protein level, FLC and isotype specific HLC pairs were also analyzed. Evolving change in M-protein level according to SPE was defined as ³ 10% increase within the first 6 months of diagnosis (if M-protein was ³ 30 g/L) and/or ³ 25% increase within the first 12 months (for any level of M-protein); evolving change according to HLC was defined as a ³ 10% increase in the involved pair. A sequential increase in each of three or more consecutive measurements from diagnosis was considered an evolving change regardless of its magnitude. Results: The clinical characteristics of the total of patients, as well as of the patients with evolving changes in M-protein according to HLC are summarized in Table 1. During the study period, 5/30 (17%) of patients demonstrated an evolving behavior of the M-protein according to SPE. Four of these patients (4/5) also showed a progressive increase in the M-protein in the HLC measurements. One patient showed stable HLC levels even though both the M-protein and the involved FLC progressively increased. This patient was of intermediate and low risk according to Mayo Clinic and PETHEMA scores, respectively. On follow up, no progressive suppression of the isotype-specific uninvolved HLC pair or increase in the FLC ratio was noted, and there have been no signs of progression after a follow up of 3 years. According to involved HLC-pair levels, 12/30 (40%) of patients demonstrated an evolving behavior. Five out of 7 patients that were not classified as evolving by SPE, were IgA isotype. Eight out of 12 patients showed severe isotype-specific suppression of the uninvolved HLC-pair (> 50% below lower level of normal) as well as a highly abnormal FLC ratio (<0.125 or >8). Three out of the 4 remaining patients showed either severe isotype-specific HLC pair suppression or highly abnormal FLC ratio in follow up measurements. Compared to patients with no "HLC-evolving pattern", evolving patients were more likely to have highly abnormal FLC ratios (90 vs. 33%, p=0.009), severe suppression of the other isotypes (64 vs. 19%, p=0,024), highly abnormal isotype-specific HLC ratios (67 vs. 33%, p=NS), severe isotype-specific HLC-pair suppression (75 vs. 50%, p=NS), and immunoparesis (67 vs. 39%p=NS). Five patients progressed to symptomatic multiple myeloma during follow up; 4 of them showed a progressive increase in the involved HLC pair from diagnosis. The remaining patient demonstrated a progressive increase in the involved HLC pair that started 19 months prior to progression, followed 4 months later with an increase in M-protein as measured by SPE. Conclusions: In our series, the Hevylite assay allowed us to identify patients with a progressive increase in M-protein (clonal heavy/light chain pair) that was not evident with SPE measurements. This "HLC evolving pattern" was associated with other risk factors for progression to symptomatic disease and with worsening of other prognostic parameters during follow up. Disclosures Rosinol: Janssen, Celgene, Amgen, Takeda: Honoraria. Bladé:Janssen: Honoraria.

scholarly journals Testing Mayo Clinic’s New 20/20/20 Risk Model in Another Cohort of Smoldering Myeloma Patients: A Retrospective Study

2021 ◽  
Vol 28 (3) ◽  
pp. 2029-2039
Author(s):  
Camille Tessier ◽  
Thomas Allard ◽  
Jean-Samuel Boudreault ◽  
Rayan Kaedbey ◽  
Vincent Éthier ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Risk Model ◽  
Risk Groups ◽  
High Risk Group ◽  
M Protein ◽  
Clinical Settings ◽  
Increased Risk ◽  
Risk Of Progression ◽  
Bone Marrow Plasma ◽  
Smoldering Myeloma

Background—smoldering multiple myeloma (SMM) risk of progression to multiple myeloma (MM) is highly heterogeneous and several models have been suggested to predict this risk. Lakshman et al. recently proposed a model based on three biomarkers: bone marrow plasma cell (BMPC) percentage > 20%, free light chain ratio (FLCr) > 20 and serum M protein > 20 g/L. The goal of our study was to test this “20/20/20” model in our population and to determine if similar results could be obtained in another cohort of SMM patients. Method—we conducted a retrospective, single center study with 89 patients diagnosed with SMM between January 2008 and December 2019. Results—all three tested biomarkers were associated with an increased risk of progression: BMPC percentage ≥ 20% (hazard ratio [HR]: 4.28 [95%C.I., 1.90–9.61]; p < 0.001), serum M protein ≥ 20 g/L (HR: 4.20 [95%C.I., 1.90–15.53]; p = 0.032) and FLCr ≥ 20 (HR: 3.25 [95%C.I., 1.09–9.71]; p = 0.035). The estimated median time to progression (TTP) was not reached for the low and intermediate risk groups and was 29.1 months (95%C.I., 3.9–54.4) in the high-risk group (p = 0.006). Conclusions—the 20/20/20 risk stratification model adequately predicted progression in our population and is easy to use in various clinical settings.

Immunoglobulin Free Light Chain Ratio Is an Independent Risk Factor for Progression of Smoldering Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1487-1487 ◽  
Author(s):  
Angela Dispenzieri ◽  
Robert A. Kyle ◽  
Jerry A. Katzmann ◽  
Dirk Larson ◽  
Joanne Benson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Light Chain ◽  
Plasma Cells ◽  
Free Light Chain ◽  
M Protein ◽  
Baseline Serum ◽  
Smoldering Multiple Myeloma ◽  
Risk Of Progression ◽  
Bone Marrow Plasma

Abstract Background: Smoldering multiple myeloma (SMM) is an asymptomatic plasma cell proliferative disorder with a high risk of progression to symptomatic multiple myeloma. Identification of risk factors that predict progression of SMM to symptomatic MM could identify higher risk patients who might benefit from chemoprevention or more intensive surveillance. We hypothesized that increased monoclonal free kappa or lambda immunoglobulin light chains in smoldering myeloma (SMM), as detected by the serum free light chain (FLC) assay, indicates an increased the risk of progression to active myeloma. Methods: Of 276 pathologically confirmed SMM patients seen at the Mayo Clinic from 1970 to 1995, baseline serum samples obtained within 30 days of diagnosis were available in 273. Results: At a median follow-up of surviving patients of 12.4 years, transformation to active disease has occurred in 161 (59%) patients. An abnormal FLC ratio was present at baseline in 90% of patients. The best break-point for predicting risk of progression was a FLC ratio less than or equal to 0.125 or greater than or equal to 8 (hazard ratio, 2.3; 95% CI, 1.6–3.2) [Figure 1]. The extent of abnormality of FLC ratio was independent of SMM risk categories defined by number of plasma cells in the bone marrow and size of serum M-proteins (bone marrow plasma cells ≥ 10% and serum M protein ≥ 3 g/dL; bone marrow plasma cells ≥ 10% but serum M protein &lt; 3 g/dL; and serum M protein ≥ 3 g/dL but bone marrow plasma cells &lt; 10%). Incorporating the FLC ratio into the risk model, the division of patients into high-, intermediate-, and low-risk groups is 28, 42, and 30% with 5 year progression rates of 76, 51, and 25%, respectively [Figure 2]. Conclusions: The serum immunoglobulin FLC ratio is an important additional determinant of clinical outcome in patients with SMM. Figure Figure Figure Figure

scholarly journals Smoldering Multiple Myeloma

2015 ◽  
Vol 2015 ◽  
pp. 1-7
Author(s):  
Minjie Gao ◽  
Guang Yang ◽  
Yuanyuan Kong ◽  
Xiaosong Wu ◽  
Jumei Shi
Keyword(s):  
Multiple Myeloma ◽  
Early Treatment ◽  
Plasma Cells ◽  
Intermediate Stage ◽  
Organ Damage ◽  
M Protein ◽  
Smoldering Multiple Myeloma ◽  
Risk Of Progression ◽  
Bone Marrow Plasma ◽  
Peripheral Blood Plasma

Smoldering multiple myeloma (SMM) is an asymptomatic precursor stage of multiple myeloma (MM) characterized by clonal bone marrow plasma cells (BMPC) ≥ 10% and/or M protein level ≥ 30 g/L in the absence of end organ damage. It represents an intermediate stage between monoclonal gammopathy of undetermined significance (MGUS) and symptomatic MM. The risk of progression to symptomatic MM is not uniform, and several parameters have been reported to predict the risk of progression. These include the level of M protein and the percentage of BMPC, the proportion of immunophenotypically aberrant plasma cells, and the presence of immunoparesis, free light-chain (FLC) ratio, peripheral blood plasma cells (PBPC), pattern of serum M protein evolution, abnormal magnetic resonance imaging (MRI), cytogenetic abnormalities, IgA isotype, and Bence Jones proteinuria. So far treatment is still not recommended for SMM, because several trials suggested that patients with SMM do not benefit from early treatment. However, the Mateos et al. trial showed a survival benefit after early treatment with lenalidomide plus dexamethasone in patients with high-risk SMM. This trial has prompted a reevaluation of early treatment in an asymptomatic patient population.

Prognostic Value of Circulating Plasma Cells in Monoclonal Gammopathy of Undetermined Significance

2005 ◽  
Vol 23 (24) ◽  
pp. 5668-5674 ◽  
Author(s):  
Shaji Kumar ◽  
S. Vincent Rajkumar ◽  
Robert A. Kyle ◽  
Martha Q. Lacy ◽  
Angela Dispenzieri ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Gammopathy ◽  
Prognostic Value ◽  
Plasma Cells ◽  
Progression Free Survival ◽  
M Protein ◽  
Free Survival ◽  
Risk Of Progression ◽  
Plasma Cell Disorder ◽  
Undetermined Significance

Purpose Monoclonal gammopathy of undetermined significance (MGUS) progresses to multiple myeloma or another related plasma cell disorder (PCD) at a rate of approximately 1% per year. Identification of patients with MGUS at high risk of progression will allow development of preventive strategies. We studied the prognostic value of circulating plasma cells (PCs) in patients with MGUS to predict progression. Patients and Methods Patients were eligible for this retrospective analysis if they were seen at the Mayo Clinic between 1984 and 1997, were diagnosed with MGUS, and had an analysis of the peripheral blood for circulating PCs by the slide-based immunofluorescence method. Patients were observed for progression to another PCD. Results Three hundred twenty-five patients were eligible and 63 (19%) had circulating PCs. Patients with circulating PCs were twice as likely (hazard ratio, 2.1) to experience progression to another PCD (most commonly myeloma), compared with those without circulating PCs (95% CI, 1.1 to 4.3; P = .03). In patients with circulating PCs, the median progression-free survival was 138 months compared with a median not yet reached for those without circulating PCs (P = .028). The median overall survival also was shorter for those with circulating PCs. Other factors with prognostic value were high levels of M protein and non–immunoglobulin G heavy-chain type. Conclusion The presence of circulating PCs, especially when combined with other known prognostic factors such as M protein concentration and immunoglobulin isotype, identify a group of individuals with MGUS at higher risk of progression to overt multiple myeloma.

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