THE IMPACT OF THE UPDATED IMWG DIAGNOSTIC CRITERIA IN A REAL-LIFE SMM COHORT : A SINGLE CENTER EXPERIENCE
(Abstract release date: 05/18/17)
EHA Library. Vlummens P. 05/18/17; 182669; PB1955
Philip Vlummens
Contributions
Contributions
Abstract
Abstract: PB1955
Type: Publication Only
Background
Recently, an update of the diagnostic criteria for smoldering multiple myeloma (SMM) & multiple myeloma (MM) was published by the International Myeloma Working Group (IMWG). In addition to CRAB criteria, 3 biomarkers of disease were introduced being (i) the presence of >60% clonal bone marrow plasma cells (BMPC), (ii) a serum free light chain ratio (FLC-ratio) >100 & (iii) the presence of >1 focal lesion on whole-body MRI (WBMRI). The introduction of these biomarkers has been shown to identify patients having a 70-80% risk of progression to MM over a 2-year time period.
Aims
To evaluate the impact of IMWG criteria in routine practice, focussing on (i) the prevalence of these biomarkers, (ii) the diagnostic strength of BMPC estimation using bone marrow aspirate versus biopsy & (iii) the added role of dynamic contrast-enhanced WBMRI (DCEMRI) in the evaluation of SMM patients.
Methods
We retrospectively identified 28 SMM cases diagnosed between 01/01/09-31/12/14. Sufficient data for analysis was available for 25 patients. All patients underwent standard clinical & laboratory evaluation, bone marrow examination & WBMRI (T1- (+/-Gd) & T2-weighted sequences, diffusion-weighted sequences & additional DCEMRI sequences using time intensity curves).
Time to progression (TTP) is defined as time from diagnosis until MM development. Overall survival (OS) is defined as time from diagnosis until death from any cause. Survival analysis was performed using the Kaplan-Meier method & significance was tested using the log-rank algorithm. Intergroup analysis was performed using non-parametric rank-based analysis & correlation was calculated using the Pearson coefficient. Reported p-values are 2-sided with a significance level of 5%.
Results
Median follow-up was 64,1 months (analysis performed on 01/02/2017). No patients had a FLC-ratio >100 at time of diagnosis. Also, no patients with >60% of clonal BMPCs were seen. In 20 patients BMPC counts using both aspirate & biopsy were available. Analysis showed a significant higher estimate of BMPC levels using biopsy (14,8%, SD 4,99) versus aspirate (8,45%, SD 6,59) (p=0,002). Sensitivity of bone marrow aspirate was calculated to be 30% considering the 10% BMPC cut-off. Correlation between bone marrow aspirate & biopsy was found in 26,6% of cases.
WBMRI-positivity was seen in 9 patients (36%). Progression was seen in 7/9 patients (78%) where only 1/16 WBMRI-negative patients (6,3%) developed MM (p<0,001). Median TTP was 19,9 months versus not-reached, respectively (p<0,001). No OS difference was seen between both groups (p=0,453). DCEMRI was positive in 14 patients (56%) thus identifying 5 additional WBMRI-negative patients with measurable bone marrow involvement. No significant difference concerning progression risk was however seen between WBMRI-negative patients being DCEMRI-positive (5/19, 26,3%) or -negative (14/19, 73,7%) (p=0,317).
Analysis of baseline data revealed no significant difference concerning age, sex, genetic aberrations or the type of the monoclonal protein between both groups. In patients developing MM, progression was seen based on the development of anemia (5/8, 62,5%), bone pain (3/8, 37,5%), hypercalcemia (1/8, 12,5%) & the development of punched-out lesions (4/8, 50%). No renal insufficiency was seen.
Conclusion
Our data shows that WBMRI-positivity was the most frequent biomarker in a routine clinical setting. WBMRI-positivity, according to IMWG-criteria, clearly identifies patients with an increased risk of progression as was already shown previously. Although increasing the sensitivity of WBMRI, addition of DCEMRI-sequences didn't have an added benefit. Our sample size was however relatively small. And although IMWG-guidelines do not state clear requirements concerning the preferred type of bone marrow evaluation, our data shows that a bone marrow biopsy can never be ommited in suspected cases of SMM, as an aspirate alone clearly lacks diagnostic strength.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Bone marrow biopsy, Smoldering, Myeloma, MRI
Abstract: PB1955
Type: Publication Only
Background
Recently, an update of the diagnostic criteria for smoldering multiple myeloma (SMM) & multiple myeloma (MM) was published by the International Myeloma Working Group (IMWG). In addition to CRAB criteria, 3 biomarkers of disease were introduced being (i) the presence of >60% clonal bone marrow plasma cells (BMPC), (ii) a serum free light chain ratio (FLC-ratio) >100 & (iii) the presence of >1 focal lesion on whole-body MRI (WBMRI). The introduction of these biomarkers has been shown to identify patients having a 70-80% risk of progression to MM over a 2-year time period.
Aims
To evaluate the impact of IMWG criteria in routine practice, focussing on (i) the prevalence of these biomarkers, (ii) the diagnostic strength of BMPC estimation using bone marrow aspirate versus biopsy & (iii) the added role of dynamic contrast-enhanced WBMRI (DCEMRI) in the evaluation of SMM patients.
Methods
We retrospectively identified 28 SMM cases diagnosed between 01/01/09-31/12/14. Sufficient data for analysis was available for 25 patients. All patients underwent standard clinical & laboratory evaluation, bone marrow examination & WBMRI (T1- (+/-Gd) & T2-weighted sequences, diffusion-weighted sequences & additional DCEMRI sequences using time intensity curves).
Time to progression (TTP) is defined as time from diagnosis until MM development. Overall survival (OS) is defined as time from diagnosis until death from any cause. Survival analysis was performed using the Kaplan-Meier method & significance was tested using the log-rank algorithm. Intergroup analysis was performed using non-parametric rank-based analysis & correlation was calculated using the Pearson coefficient. Reported p-values are 2-sided with a significance level of 5%.
Results
Median follow-up was 64,1 months (analysis performed on 01/02/2017). No patients had a FLC-ratio >100 at time of diagnosis. Also, no patients with >60% of clonal BMPCs were seen. In 20 patients BMPC counts using both aspirate & biopsy were available. Analysis showed a significant higher estimate of BMPC levels using biopsy (14,8%, SD 4,99) versus aspirate (8,45%, SD 6,59) (p=0,002). Sensitivity of bone marrow aspirate was calculated to be 30% considering the 10% BMPC cut-off. Correlation between bone marrow aspirate & biopsy was found in 26,6% of cases.
WBMRI-positivity was seen in 9 patients (36%). Progression was seen in 7/9 patients (78%) where only 1/16 WBMRI-negative patients (6,3%) developed MM (p<0,001). Median TTP was 19,9 months versus not-reached, respectively (p<0,001). No OS difference was seen between both groups (p=0,453). DCEMRI was positive in 14 patients (56%) thus identifying 5 additional WBMRI-negative patients with measurable bone marrow involvement. No significant difference concerning progression risk was however seen between WBMRI-negative patients being DCEMRI-positive (5/19, 26,3%) or -negative (14/19, 73,7%) (p=0,317).
Analysis of baseline data revealed no significant difference concerning age, sex, genetic aberrations or the type of the monoclonal protein between both groups. In patients developing MM, progression was seen based on the development of anemia (5/8, 62,5%), bone pain (3/8, 37,5%), hypercalcemia (1/8, 12,5%) & the development of punched-out lesions (4/8, 50%). No renal insufficiency was seen.
Conclusion
Our data shows that WBMRI-positivity was the most frequent biomarker in a routine clinical setting. WBMRI-positivity, according to IMWG-criteria, clearly identifies patients with an increased risk of progression as was already shown previously. Although increasing the sensitivity of WBMRI, addition of DCEMRI-sequences didn't have an added benefit. Our sample size was however relatively small. And although IMWG-guidelines do not state clear requirements concerning the preferred type of bone marrow evaluation, our data shows that a bone marrow biopsy can never be ommited in suspected cases of SMM, as an aspirate alone clearly lacks diagnostic strength.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Bone marrow biopsy, Smoldering, Myeloma, MRI
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