Continued monoclonal protein response beyond day 100 after auto-transplantation for multiple myeloma.

8587 Background: Patients (pts) undergoing an auto-transplant (ASCT) for multiple myeloma (MM) have disease assessment approximately 100 days later. This result may direct decisions of further therapy versus observation. However, some pts continue to experience a decline in their serum or urine monoclonal (M) - protein after day 100 without more therapy. Little is known about the prevalence and significance of this phenomenon. Methods: We identified 903 MM pts who underwent ASCT within 12 months (mos) of diagnosis (Dx) at our institution. Their day 100 post-ASCT M-protein from serum and urine electrophoresis with immunofixation as well as serum free light chains were compared to subsequent values during follow-up. The IMWG criteria were used to evaluate response. Results: Of the pts included, 510 (56%) were male and median age at ASCT was 59 (range 28-76). Median follow up from Dx and ASCT was 82 mos (95% CI; 75 - 86) and 74 mos (95% CI; 70 - 79) respectively. There were 453 (50%) pts seen in follow-up who had not achieved a CR at Day 100 nor initiated on maintenance therapy. Of these pts, 167 (37%) had a further decrease in their M-protein after day 100 at a median of 9.4 mos (95% CI; 8 – 10) post-ASCT. Given the time taken for maximal response, we assessed patients’ clinical response at one year post-ASCT. Compared to patients who did not have further clinical response between day 100 and 1 year, pts experiencing further response had a longer time to next therapy (TTNT) (43 mos vs. 17 mos, P < 0.001) as well as overall survival (OS) (96 mos vs. 62 mos, P < 0.001). Positive predictors for continued response included having an IgG isotype, evolution from a pre-existing MGUS, smoldering myeloma or solitary plasmacytoma and a Day 100 bone marrow plasma cell < 3%. In a multivariate analysis, elevated creatinine at Dx and lack of continued response predicted for shorter TTNT and OS post-ASCT. Older age and high-risk MM by FISH also predicted a shorter OS. Conclusions: In MM pts undergoing ASCT, continued M - protein response was seen in a third of the pts lacking a CR at day 100. This phenomenon appears prognostic and must be considered when interpreting studies evaluating post-ASCT response and the need for further therapy.

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The Natural History of Smoldering (Asymptomatic) Multiple Myeloma.

Blood ◽

10.1182/blood.v106.11.3396.3396 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3396-3396 ◽

Cited By ~ 4

Author(s):

Robert Kyle ◽

Ellen Remstein ◽

Terry Therneau ◽

Angela Dispenzieri ◽

Paul Kurtin ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Plasma Cell ◽

Light Chain ◽

Plasma Cells ◽

M Protein ◽

Cell Content ◽

Bone Marrow Plasma ◽

M Spike

Abstract Smoldering multiple myeloma (SMM) is characterized by a serum M protein ≥ 3g/dL and/or 10% or more of plasma cells in the bone marrow. However, the definition is not standardized, and it is not known whether both serum M protein levels and bone marrow plasma cell counts are necessary for diagnosis or if one parameter is sufficient. We reviewed the medical records and bone marrows of all patients from Mayo Clinic seen within 30 days of recognition of an IgG or IgA M protein ≥ 3g/dL or a bone marrow containing ≥ 10% plasma cells from 1970 to 1995. This allows for a minimum potential follow-up of 10 years. Patients with end-organ damage at baseline from plasma cell proliferation, including active multiple myeloma (MM) and primary amyloidosis (AL) and those who had received chemotherapy were excluded. A differential of the bone marrow aspirate coupled with the bone marrow biopsy morphology and immunohistochemistry using antibodies directed against CD138, MUM-1 and Cyclin D1 were evaluated in every case in order to estimate the plasma cell content. In all, 301 patients fulfilled either of the criteria for SMM. Their median age was 64 years and only 3% were less than 40 years of age; 60% were male. The median hemoglobin value was 12.9 g/dL; 7% were less than 10 g/dL, but the anemia was unrelated to plasma cell proliferation. IgG accounted for 75%, IgA 22%, and biclonal proteins were found in 3%. The serum light-chain was κ in 67% and λ in 33%. The median serum M spike was 2.9 g/dL; 11% were at least 4.0 g/dL. Uninvolved serum immunoglobulins were reduced in 81%; only 1 immunoglobulin was reduced in 31% and both were decreased in 50%. The urine contained a monoclonal κ protein in 36% and λ in 18% and 46% were negative. The median size of the urine M spike was 0.04 g/24h; only 5 (3%) were > 1 g/24h. The median bone marrow plasma cell content was 15 – 19%; 10% had less than 10% plasma cells, while 10% had at least 50% plasma cells in the bone marrow. Cyclin D-1 was expressed in 17%. Patients were categorized into 3 groups: Group 1, serum M protein ≥ 3g/dL and bone marrow containing ≥ 10% plasma cells (n= 113, 38%); Group 2, bone marrow plasma cells ≥ 10% but serum M protein < 3g/dL (n= 158, 52%); Group 3, serum M protein ≥ 3g/dL but bone marrow plasma cells < 10% (n= 30, 10%). During 2,204 cumulative years of follow-up 85% died (median follow-up of those still living 10.8 years), 155 (51%) developed MM, while 7 (2%) developed AL. The overall rate of progression at 10 years was 62%; median time to progression was 5.5 yrs. The median time to progression was 2.4, 9.2, and 19 years in groups 1, 2, and 3 respectively; correspondingly at 10 years, progression occurred in 76%, 59%, and 32% respectively. Significant risk factors for progression with univariate analysis were serum M spike ≥ 4g/dL (p < 0.001), presence of IgA (p = 0.003), presence of urine light chain (p = 0.006), presence of λ urinary light chain (p = 0.002), bone marrow plasma cells ≥ 20% (p < 0.001) and reduction of uninvolved immunoglobulins (p < 0.001). The hemoglobin value, gender, serum albumin, and expression of cyclin D-1 were not of prognostic importance. On multivariate analysis, the percentage of bone marrow plasma cells was the only significant factor predicting progression to MM or AL.

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

Current Oncology ◽

10.3390/curroncol28030188 ◽

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.

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NCCN Guidelines Insights: Multiple Myeloma, Version 1.2020

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2019.0049 ◽

2019 ◽

Vol 17 (10) ◽

pp. 1154-1165 ◽

Cited By ~ 32

Author(s):

Shaji K. Kumar ◽

Natalie S. Callander ◽

Jens Hillengass ◽

Michaela Liedtke ◽

Muhamed Baljevic ◽

...

Keyword(s):

Multiple Myeloma ◽

Supportive Care ◽

Monoclonal Gammopathy ◽

Solitary Plasmacytoma ◽

Nccn Guidelines ◽

Smoldering Myeloma

The NCCN Guidelines for Multiple Myeloma provide recommendations for diagnosis, workup, treatment, follow-up, and supportive care for patients with monoclonal gammopathy of renal significance, solitary plasmacytoma, smoldering myeloma, and multiple myeloma. These NCCN Guidelines Insights highlight some of the important updates and changes in the 1.2020 version of the NCCN Guidelines for Multiple Myeloma.

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How we manage smoldering multiple myeloma

Hematology Reports ◽

10.4081/hr.2020.8951 ◽

2020 ◽

Vol 12 (s1) ◽

Author(s):

Alessandra Romano ◽

Claudio Cerchione ◽

Concetta Conticello ◽

Giovanni Martinelli ◽

Francesco Di Raimondo

Keyword(s):

Plasma Cells ◽

Organ Damage ◽

Prognostic Models ◽

Clinical Approach ◽

High Efficacy ◽

Clinical Practices ◽

Bone Marrow Plasma ◽

Asymptomatic Stage ◽

Smoldering Myeloma

Smoldering myeloma (SMM) is an asymptomatic stage characterized by bone marrow plasma cells infiltration between 10-60% in absence of myeloma-defining events and organ damage. Until the revision of criteria of MM to require treatment, two main prognostic models, not overlapping each other, were proposed and used differently in Europe and in US. Novel manageable drugs, like lenalidomide and monoclonal antibodies, with high efficacy and limited toxicity, improvement in imaging and prognostication, challenge physicians to offer early treatment to high-risk SMM. Taking advantage from the debates offered by SOHO Italy, in this review we will update the evidence and consequent clinical practices in US and Europe to offer readers a uniform view of clinical approach at diagnosis, follow-up and supportive care in the SMM setting.

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

Blood ◽

10.1182/blood.v106.11.5080.5080 ◽

2005 ◽

Vol 106 (11) ◽

pp. 5080-5080 ◽

Cited By ~ 1

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<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.

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The Utility of the Follow-up with Serum Free Light Chain After Autologous Stem Cell Transplantation in Multiple Myeloma Patients with Measurable M-Protein.

Blood ◽

10.1182/blood.v114.22.4878.4878 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4878-4878

Author(s):

Byeong Seok Sohn ◽

Eun Kyoung Kim ◽

Dok Hyun Yoon ◽

Myoung Joo Kang ◽

Dae Ro Choi ◽

...

Keyword(s):

Multiple Myeloma ◽

Progressive Disease ◽

Response Assessment ◽

M Protein ◽

Response Criteria ◽

Absolute Increase ◽

Serum Free Light Chain ◽

Measurable Disease ◽

Transplant Registry

Abstract Abstract 4878 Introduction According to international uniform response criteria for multiple myeloma suggested in 2006, the response assessment for patients with oligo- and non-secretory multiple myeloma (MM) can be evaluated by the serum free light chain (FLC) assay. Although the FLC response criteria are not applicable in MM patients with measurable disease, there were several reports suggesting that serial measurement of serum FLC may detect relapse earlier than protein electrophoresis studies. We, therefore, investigated the preceding changes in serial serum FLC assay until progressive disease was confirmed by the international uniform response criteria in post-ASCT patients with measurable disease. Patients and Method We included patients from the AMC MM transplant registry, who met the following (1) undertook ASCT for measurable disease (2) showed, at least, two serial response assessment of stable disease or complete response before progression or relapse by serum or urine M-protein, (3) had periodic serum FLC assay simultaneously tested with serum and/or urine protein electrophoresis at each response assessment. Progressive disease (PD) was defined by increase of ≥ 25% from baseline in serum M-protein (the absolute increase must be ≥ 0.5mg/dL) and/or urine M-component (the absolute increase must be ' 200mg/24h) according to international uniform response criteria. In this investigation, significant increase in the difference between involved and uninvolved FLC (dFLC) and in the involved FLC (iFLC) was defined by increase of ≥ 25% from baseline. The positive predictive value of three cutoff levels for absolute increase, 10mg/L, 20mg/L, 100mg/L, were evaluated for both dFLC and iFLC provided serum FLC ratio was abnormal. Each patient was followed up with 1-3 month intervals according to the protocol for MM patients after ASCT. Result A total 29 patients of 138 patients in the AMC MM transplant registry satisfied above criteria. When the cut-off level for absolute increase was defined as 100mg/L, the significant increase of iFLC in 12 patients (41%) and dFLC in 11 patients (38%) preceded or accompanied with the time of progressive disease observed by M-protein. The median value of preceding time was 2 month (range -5 - 0). When the cut-off level was defined as 20mg/L, the sustained significant increase of iFLC in 21 patients (72%) and dFLC in 17 patients (59%) preceded or accompanied with the time of progressive disease with median of 2 month (range -9 - 0) and 2 month (range, -5 – 0), respectively. At the cut-off level of 10mg/L, the sustained significant increase of iFLC in 23 patients (79%) and dFLC in 21 patients (72%) preceded or accompanied with the time of progressive disease observed by M-protein. The median of preceding time was 2 month (range -11 - 0) and 1 month (range, -11 - 0), respectively. Twenty-eight dFLC values were observed as negative values out of a total 123 data from 29 patients. Of these values, 12 were below normal iFLC concentration, 14 within normal range of iFLC (kappa 8.5 - 23.7 mg/L, lambda 9.5 - 23.5 mg/L), and 2 above normal iFLC concentration. Conclusion In this study, about 70% of patients showed sustained significant increase of iFLC that preceded or accompanied the time of progressive disease observed by M-protein by a median of 2 months at a cut-off absolute increase of 20mg/L. Although there is a subtle difference in prediction rates according to defined cut-off levels, serial follow up of iFLC and sustained increase by 25% during follow-up seems to have a utility in the prediction of progression after ASCT. In addition, interpretations of dFLC may be difficult as it is frequently observed as negative value in post-ASCT MM patients. Therefore, the serial and sustained increase of iFLC may be useful in lower iFLC concentrations. However, there should be more validation with large patients' population. Disclosures No relevant conflicts of interest to declare.

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Serum Free Light Chain Ratio in Distinguishing Smoldering Multiple Myeloma From Active Multiple Myeloma,

Blood ◽

10.1182/blood.v118.21.3948.3948 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3948-3948

Author(s):

Jeremy T Larsen ◽

Shaji Kumar ◽

S. Vincent Rajkumar

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Predictive Value ◽

Plasma Cells ◽

Organ Damage ◽

End Organ Damage ◽

Cut Point ◽

Smoldering Multiple Myeloma ◽

Bone Marrow Plasma

Abstract Abstract 3948 Background: Smoldering multiple myeloma (SMM) is an asymptomatic precursor disease of multiple myeloma, and is defined by excess bone marrow plasma cells and monoclonal protein without evidence of end-organ damage (hypercalcemia, renal insufficiency, anemia, or bone lesions [CRAB]). The identification of SMM patients with more aggressive underlying disease remains a challenge. We hypothesize that SMM is a clinical entity comprised of both premalignant, high-risk MGUS and early multiple myeloma in transition to malignant disease, which may be differentiated with the use of the serum FLC (FLC) ratio. Methods: This was a retrospective analysis of 586 patients with newly diagnosed SMM from 1970–2010 with available stored serum samples around the time of diagnosis to be utilized for quantification of FLC ratios. SMM was defined by the International Myeloma Working Group 2003 definition; serum M-protein ≥ 3 g/dL and/or ≥ 10% bone marrow plasma cells with no evidence of CRAB features. The immunoglobulin FLC assay (Binding Site, U.K.) was used for testing. The FLC ratio was calculated as κ/λ (reference range 0.26–1.65). The involved/uninvolved FLC ratio was recorded to simplify the reporting of data. Receiver Operating Characteristics (ROC) curves were created to assess the ability of the FLC ratio to discriminate patients who progressed to symptomatic multiple myeloma (MM) in the first 2 years or at any point during follow-up versus patients without evidence of progression. Patients with less than 24 months follow-up without progression were censored. The optimal diagnostic cut-point for FLC involved/uninvolved ratio to identify patients with progressive disease from the ROC curve was >88.6 (equivalent to <0.011 or >88.6). For ease of clinical application, the optimal value for involved/uninvolved FLC ratio was rounded to >100. Time to progression (TTP) from date of the initial FLC to active MM was calculated using Kaplan-Meier analysis and compared to patients with a high (>100) and low (<100) involved/uninvolved FLC ratio at time of SMM diagnosis. TTP within 24 months of the initial FLC was also calculated. Results: During the study period, 54% of patients progressed to active MM. On ROC analysis, a cut-point of >100 corresponded to a sensitivity of 25% (95% CI, 20.5–30.4) and specificity of 99.3% (97.3–99.9), with positive likelihood (+LR) ratio of 33.9 (38.1–41.0), negative likelihood ratio (−LR) of 0.75 (0.2–3.0), positive predictive value (PPV) of 97.6 (91.5–99.7) and negative predictive value of 53.0 (48.5–57.4). Using the ROC to assess progression to MM within 24 months (Figure 1), sensitivity was 29.6% (23.5–36.4), specificity 94.5% (91.7–96.5), +LR 5.36 (4.3–6.6), -LR 0.75 (0.5–1.1), PPV 85.8 (77.7–91.8), and NPV 54.3 (49.8–58.9). Median TTP to active MM in the FLC >100 group was 15 months (9–17) versus 52 months (44–60) in the FLC <100 group (p <.0001) [Figure 2]. In the FLC ratio >100 group, progression at 1 year was 47%, 76% at 2 years, and 90% at 3 years. Only 25% of the FLC <100 patients had progressed at 2 years. The most common progression event was bone disease (42%), followed by anemia (26%), renal impairment (23%), and hypercalcemia (5%). Conclusion: Elevation of the FLC ratio >100 (or <0.01) is highly specific for the future development of active MM, with 76% of these patients developing end-organ damage requiring therapy within 2 years. Risk of transformation to MM in the FLC <100 group was similar to previously reported rates of 10% per year for the first 5 years. Development of an FLC ratio >100 is associated with increasing disease burden and in this study behaved in a malignant fashion rather than a precursor state. The FLC is a simple and useful predictor of progression to MM in SMM, and patients with FLC ratios of <0.01 or >100 within the first 2 years of SMM diagnosis should be monitored especially closely. Future studies are needed to determine optimum cutoffs for FLC ratio to where a change in definition of MM could be considered. Disclosures: No relevant conflicts of interest to declare.

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Predictive Significance of Serum Beta 2-Microglobulin Levels and M-Protein Velocity for Symptomatic Progression of Smoldering Multiple Myeloma

Blood ◽

10.1182/blood.v124.21.3379.3379 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3379-3379 ◽

Cited By ~ 7

Author(s):

Tsuyoshi Muta ◽

Shinsuke Iida ◽

Kosei Matsue ◽

Kazutaka Sunami ◽

Jun Isoda ◽

...

Keyword(s):

Multiple Myeloma ◽

Cumulative Incidence ◽

Plasma Cells ◽

M Protein ◽

Bone Lesions ◽

Landmark Point ◽

Protein Levels ◽

Lytic Bone Lesions ◽

Bone Marrow Plasma ◽

Beta 2 Microglobulin

Abstract Background: Smoldering multiple myeloma (SMM) has been defined as precursor state to symptomatic multiple myeloma (MM). Mayo Clinic demonstrated that the presence of bone marrow plasma cells (BMPC) ≥ 10% and M protein levels ≥ 3 g/dL significantly associated with early progression to symptomatic MM and the serum free-light chain (FLC) ratio of < 0.125 or 8 < was an important additional predictors of progression. PETHEMA showed that the proportion of aberrant plasma cells (aPCs) within the BMPC > 95% as assessed by flow cytometry was another important variable for progression. However, NIH demonstrated the discordance of these two risk models. The aim of this project is to develop the method to predict the symptomatic progression more definitely by simple parameters, usually available at medical practice. Methods: We employed the nation-wide retrospective study. The clinical data of SMM patients were collected from 61 medical centers in Japan and risk predictors of progression to symptomatic MM were analyzed. The diagnosis of SMM is made by the presence of the ratio of bone marrow plasma cells (BMPCs) ≥ 10% or serum M-protein levels ≥ 3 g/dL, and the absence of any myeloma derived end-organ damage. Eligible patients were aged 18 to 90 years, previously untreated, and diagnosed between 2000 and 2012. This study was approved by the institutional review board at all participating institutions. Results: Total 301 patients fulfilled the inclusion criteria. The median age was 67 years (rang 27 to 90). IgG is the major (80%) compared to IgA (15%) or Bence Jones protein (3%). Total 145 patients developed to symptomatic MM. The symptoms consisted of anemia in 66%, lytic bone lesions in 43%, and renal impairment in 10%. Both anemia and lytic bone lesions were seen in 16%. The median time to progression was 4.3 years. The cumulative incidence of progression was 30.7% at 2 years, 50.0% at 4 years, 59.8% at 6 years, and 68.6% at 8 years. Based on multivariate analysis, we firstly identify the serum beta 2-microglobulin (B2MG) levels ≥ 2.5 mg/L as a predictor for the early progression (HR 1.59; 95% CI, 1.11 to 2.29, p = 0.01), as well as the known factors: presence of both BMPC ≥ 10% and M protein levels ≥ 3 g/dL (HR 1.89; 95% CI, 1.31 to 2.73, p = 0.0007), IgA or Bence Jones type (HR:1.61; 95%CI, 1.04 to 2.49, p = 0.03), and immunoparesis (HR:1.88; 95%CI, 1.14 to 3.08, p = 0.01). FLC ratio was examined in 52 patients. A significant association with high risk of progression was observed in patients with FLC ratio of < 0.0625 or 16 < (P = 0.04), but not in those with the ratio of < 0.125 or 8 < (P = 0.09). Cytogenetic abnormality was examined with FISH in 82 patients. The cumulative incidence of progression in patients with either t(4;14), t(14;16), or del(17p) was not significantly different from those without such chromosomal aberration (P = 0.4). Notably, we firstly focused on the rate of rise of the M-protein levels over time which is referred to as the "M-protein velocity". We employed the linear regression analysis to estimate the gradient to assess the M-protein velocity of each patient. The receiver operating characteristics curve analysis showed that the M-protein velocity of 1.035 mg/dL/day was a risk-stratification cut-off point with a high specificity of 0.96 and with a moderate sensitivity of 0.60. Based on the landmark analysis, the serum B2MG levels ≥ 2.5 mg/L at diagnosis (HR 2.76; 95% CI, 1.69 to 4.51, P = 5 x 10–5) and the M-protein velocity > 1 mg/dL/day before the 18-month landmark point (HR 2.27; 95% CI, 1.30 to 3.95, P = 4 x 10–3) had independently correlated with subsequent progression to symptomatic MM. The cumulative incidence of progression of the patients with both the serum B2MG levels ≥ 2.5 mg/L at diagnosis and the M-protein velocity > 1 mg/dL/day showed 67.5% at 2 years, 75.6% at 3 years and 100% at 6.3 years after the landmark point. Conclusions: We identify the novel risk factors consisted of serum B2MG levels ≥ 2.5 mg/L and the M-protein velocity > 1 mg/dL/day for subsequent symptomatic progression. Theoretically, it is possible to emphasis that the serum B2MG levels represent the initial tumor burden of SMM and the M-protein velocity reflects the the growth rate of tumor cells. These results also suggest that the quantification of time-dependent change of measured values should be taken into consideration for the precise prediction of symptomatic progression. This study is supported by the National Cancer Center Research and Development Fund in Japan. Disclosures No relevant conflicts of interest to declare.

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Inion Bony Solitary Plasmocytoma: A Case Report

Iranian Journal of Neurosurgery ◽

10.32598/irjns.6.2.5 ◽

2020 ◽

Vol 6 (2) ◽

pp. 83-88

Author(s):

Vivek Agrawal ◽

◽

Kunal M.Ch Dholakia ◽

Keyword(s):

Multiple Myeloma ◽

Brain Mri ◽

Residual Tumor ◽

Myeloma Cell ◽

Venous Sinus ◽

Solitary Plasmacytoma ◽

Systemic Involvement ◽

Bony Lesion ◽

One Year

ackground and Importance: Plasma Cell Dyscrasias (PCD) are a heterogeneous group of diseases having a spectrum from multiple myeloma to solitary plasmacytoma, a rare subtype, which constitutes 2 to 5% of all PCD. It typically involves axial bones but the involvement of skull bone is very rare. Case Presentation: We are reporting a case of inion bony lesion with venous sinus infiltration in a 55-year-old male patient, presented with pain, imbalance in walking, and swelling in the occipital region. Brain MRI suggested an extra-axial lesion with skull involvement and venous sinus infiltration. The tumor was infiltrating into the sinus with patent torcular venous confluence. Tumor decompression followed by radiosurgery of residual lesion was considered in pre-operative surgical planning. It was diagnosed as a case of myeloma cell disease on histopathology. Postoperative myeloma work-up confirmed the absence of any systemic involvement. The patient was given a course of radiotherapy. Conclusion: One-year follow-up with repeated MRI and myeloma investigations in the 3rd month, 6th months, and 1 year did not show any finding suggestive of progression to multiple myeloma. The follow-up of brain MRI showed a complete resolution of the residual tumor.

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Tracking Daratumumab Clearance Using Mass Spectrometric Approaches: Implications on M Protein Monitoring and Reusing Daratumumab

Blood ◽

10.1182/blood-2021-153209 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2707-2707

Author(s):

Nadine Abdallah ◽

David L Murray ◽

Angela Dispenzieri ◽

Prashant Kapoor ◽

Morie A. Gertz ◽

...

Keyword(s):

Multiple Myeloma ◽

Board Of Directors ◽

Plasma Cell ◽

Research Funding ◽

Univariate Analysis ◽

M Protein ◽

Urine Protein ◽

Advisory Committees ◽

Plasma Cell Disorders

Abstract Background: MASS-FIX is a screening method for serum and urine monoclonal proteins in multiple myeloma and related plasma cell disorders, which uses immunoglobulin enrichment coupled with matrix-assisted laser desorption ionization time-of-flight mass-spectrometry (MALDI-TOF). In addition to superior sensitivity over conventional gel-based techniques, MASS-FIX can distinguish therapeutic monoclonal antibodies (MoAb) from patient's M protein. As the utilization of therapeutic MoAbs increases, it is essential to understand the persistence pattern of these therapeutic antibodies in the serum. We designed this study to evaluate the duration of daratumumab detection by MASS-FIX in the serum of treated patients. Methods: We used a prospectively maintained database at Mayo clinic to identify patients with multiple myeloma and related plasma cell disorders who were treated with a daratumumab-containing regimen anytime during their disease course and had serial MASS-FIX data available after discontinuation of daratumumab. A univariate analysis was performed to assess for factors that may impact the clearance of daratumumab. Results: We included 125 patients with plasma cell disorders who received daratumumab as first or subsequent line of treatment between March 15 th, 2016, and March 4 th, 2020. The median age was 60.2 years and 57% were male. The most common diagnoses were multiple myeloma (70%) and light chain amyloidosis (18%). Daratumumab-based treatments were initiated after a median of 28.8 (IQR: 6.4-76.3) months from initial diagnosis. The most common regimen used was daratumumab, bortezomib and dexamethasone (23%); 26% underwent transplant after daratumumab-based induction. The median duration of treatment with a daratumumab-based regimen was 208 (IQR: 99-479) days. The median follow-up from the time of daratumumab discontinuation was 457 (95% CI: 346-NR) days. By last follow up, daratumumab was not detected by MASS-FIX in 93 (74%) patients but remained detectable in 32 (26%) patients. The median time from daratumumab discontinuation to disappearance of daratumumab by MASS-FIX was 160 (IQR: 107-233) days. On univariate analysis, the presence of ≥0.5 grams of urine protein was associated with earlier disappearance of daratumumab on MASS-FIX [risk ratio (RR): 2.0, P=0.02). The median time from daratumumab discontinuation to disappearance of daratumumab on MASS-FIX was 116 (95%CI: 76-160) days in patients with urine protein ≥0.5 grams and 203 (95%CI: 162-216) days in patients with urine protein <0.5 grams (P=0.02). There was no association between the time to disappearance of daratumumab by MASS-FIX and old age ≥70 (RR: 0.9, P=0.81], male gender (RR: 0.9, P=0.60), eGFR <60 (RR: 1.0, P=0.98), daratumumab schedule (every 1/2 weeks vs >2weeks) (RR: 1.0, P=0.97), treatment duration (<200 days vs ≥200 days) ( RR: 1.0, P=0.95), or transplantation status (RR: 1.0, P=0.98). Conclusion: The therapeutic monoclonal antibody daratumumab remains detectable in the serum of treated patients by MASS-FIX for several months after discontinuation and the duration varies between individual patients. This data has implications for diagnostic and monitoring testing and may provide guidance for reuse of daratumumab in clinical trials and practice. Proteinuria is associated with earlier disappearance of daratumumab by MASS-FIX and may have implications in patients with amyloidosis and monoclonal immunoglobulin deposition disease (MIDD). Further studies are needed to identify additional factors associated with the timing of disappearance. Disclosures Murray: Mayo Clinic: Other: Has received patents for the Mass-Fix technology which has been licensed to the Binding Site with potential royalties.. Dispenzieri: Takeda: Research Funding; Alnylam: Research Funding; Pfizer: Research Funding; Oncopeptides: Consultancy; Sorrento Therapeutics: Consultancy; Janssen: Consultancy, Research Funding. Kapoor: Karyopharm: Consultancy; Cellectar: Consultancy; BeiGene: Consultancy; Pharmacyclics: Consultancy; Sanofi: Consultancy; Amgen: Research Funding; Ichnos Sciences: Research Funding; Regeneron Pharmaceuticals: Research Funding; Glaxo SmithKline: Research Funding; Karyopharm: Research Funding; Sanofi: Research Funding; Takeda: Research Funding; AbbVie: Research Funding. Gertz: Akcea Therapeutics, Ambry Genetics, Amgen Inc, Celgene Corporation, Janssen Biotech Inc, Karyopharm Therapeutics, Pfizer Inc (to Institution), Sanofi Genzyme: Honoraria; Ionis Pharmaceuticals: Other: Advisory Board; Akcea Therapeutics, Alnylam Pharmaceuticals Inc, Prothena: Consultancy; Aurora Biopharma: Other: Stock option; AbbVie Inc, Celgene Corporation: Other: Data Safetly & Monitoring. Dingli: Alexion: Consultancy; Novartis: Research Funding; Apellis: Consultancy; Janssen: Consultancy; Sanofi: Consultancy; GSK: Consultancy. Kumar: Antengene: Consultancy, Honoraria; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bluebird Bio: Consultancy; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Merck: Research Funding; Roche-Genentech: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Beigene: Consultancy; Oncopeptides: Consultancy; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Research Funding; Carsgen: Research Funding; Tenebio: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding.

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