MRI-Detectable Focal Lesions (FL) in Multiple Myeloma (MM) at Relapse Frequently Involve Novel Sites Not Involved at Diagnosis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5124-5124 ◽  
Author(s):  
Ronald Walker ◽  
L. Jones-Jackson ◽  
Eric Rasmussen ◽  
M. Miceli ◽  
Elias Anaissie ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
General Trend ◽  
M Protein ◽  
Focal Lesions ◽  
Extramedullary Tumor ◽  
Mri Scans ◽  
The Relationship ◽  
Baseline Examination

Abstract Macrofocal lesions (FL) in the medullary space are a hallmark of mm readily detected by MRI scans, both at diagnosis and at relapse. In this study we evaluated, among 25 patients enrolled in TT II, with FL at relapse and a preceding clinical CR (by M protein and marrow examinations) the relationship to presence and location of FL at diagnosis. On relapse, 17/25 (68%) had fewer FL, 5/25 (20%) had the same number of FL, 3/25 (12%) had more FL than on baseline examination. There was a general trend for the larger FL at baseline to still be present on relapse (Table 1). Despite the trend to fewer focal lesions on relapse compared to baseline, 11/25 (44%) of patients presented with FL in new sites that were not present on baseline. Finally, in relapsing patients, 4/25 (16%) presented with new sites of extramedullary tumor (EMD). These data establish that although there are usually fewer MRI-defined FL on relapse than on baseline examination, the vast majority of FL on relapse represent new areas of macrofocal disease that were not present at diagnosis. MRI FL Persisting from Baseline to Relapse (n=25) Size (cm) Baseline FL Present upon Relapse % < 0.5 1/2 50 0.5–1cm 8/10 80 1–2 cm 13/18 72 > 2 cm 10/16 63 All Sizes 26/36 72

SWOG S0120 Observational Trial for MGUS and Asymptomatic Multiple Myeloma (AMM): Imaging Predictors of Progression for Patients Treated At UAMS,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3955-3955
Author(s):  
Christoph Heuck ◽  
Rachael Sexton ◽  
Madhav Dhodapkar ◽  
Qing Zhang ◽  
Saad Usmani ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Research Funding ◽  
Cox Regression ◽  
Time Dependent ◽  
M Protein ◽  
Risk Scores ◽  
Imaging Studies ◽  
Focal Lesions ◽  
Pet Ct

Abstract Abstract 3955 Background: MGUS counts for the majority of monoclonal gammopathies and can be found in approximately 3% of adults older than 50 years. MGUS progresses to active Multiple Myeloma (MM) at a rate of 1–2% per year, thus imparting an average risk of 25% for progression (PRO) over a lifetime once diagnosed. Unfortunately no single laboratory, molecular or imaging variable can reliably predict PRO. S0120 accrued 363 patients at 69 sites across the US between January 1, 2004 and November 1, 2011, of whom 166 had MGUS and 190 AMM, defined according to IMWG criteria, on whom laboratory, gene expression and imaging studies were collected in a prospective fashion. Here we report the results of imaging studies as predictors of progression. Methods: 262 patients with evaluable follow-up were enrolled at the University of Arkansas for Medical Sciences (UAMS) site. MRI and PET-CT studies were performed at baseline and serially thereafter until PRO to symptomatic MM defined by standard variables of M-protein, bone marrow findings and CRAB criteria, according to protocol. Lab studies were performed at three months, six months and one year after registration, then every 12 months for a total of 5 years from registration as well as within 14 days of decision to discontinue observation or within 14 days of progression. MRI parameters included the number of focal lesions (FL) recognized by short TI inversion recovery (STIR) analysis of the axial bone marrow along with an account of bone marrow background intensity compared to adjacent muscles (hypo-, iso-, hyper-intense). PET-CT parameters included number of FDG-avid focal lesions (PET-FL), SUVmax of PET-FL, presence of extra-medullary disease (EMD) as well as the FDG avidity score at L5 (SUV-L5). Evaluable baseline MRI and PET studies were available for 235 and 224 patients, respectively. Results: In the 262 eligible patients enrolled and followed at UAMS, the two subgroups of MGUS and AMM differed by definition in M-protein and bone marrow plasmacytosis; in addition, IgA subclass and Hyperdiploidy molecular subgroup were overrepresented in the AMM group. Patients in the AMM group also had higher risk scores defined by the GEP 70-gene risk model (GEP70). At 24 months from study entry, 18.8% of all patients had progressed to MM (25.6% of AMM patients and 8.2% of MGUS patients) and 11.5% had begun MM therapy (15.8% of AMM patients and 4.5% of MGUS patients). Univariate Cox regression strongly indicated that age ≥ 65, serum albumin <3.5g/dL, B2M >+3.5mg/L, detection of any cytogenetic abnormalities (CA), and suppression of uninvolved light chains were adversely associated with time to PRO. The AMM-constituting features, bone marrow plasmacytosis >10%, M-protein >30g/L, and abnormal K/L ratio also conferred greater hazard of PRO. Risk scores > −0.26 and >1.5 for GEP70 and GEP80, respectively, as well as detection of focal lesions by MRI at baseline carried an elevated HR for PRO. A multivariate Cox regression showed only elevated M-protein, abnormal K/L ratio and GEP70 risk scores > =0.26 to be strongly associated with time to PRO. In the context of this MV model, disease subtype (AMM v MGUS) was insignificant. Inclusion of development of MRI-FL or and PET-FL as time-dependent variables showed that they were associated with time to PRO with HRs of 27.12 and 32.18 respectively. Abnormal K/L ratio and elevated M-protein were lost in this MV model. Analyzing variables linked to initiation of MM therapy, abnormal K/L ratio, elevated BM plasmacytosis, elevated M-protein, GEP70 risk scores >-0.26 as well as detection of MRI-FL at baseline (≥1 FL: HR=4.90; ≥3FL: HR=10.00) were univariately significant. On multivariate analysis, abnormal K/L ratio, elevated M-protein and GEP70 risk scores > – 0.26 were associated with time to treatment for MM. Inclusion of development of MRI-FL or PET-FL as a time dependent variable were associated with time to treatment with HRs of 29.12 and 36.50 respectively. Conclusion: To our knowledge, this is the first comprehensive effort that has used available imaging modalities along with established laboratory and pathology investigations in an attempt to distinguish features predictive of PRO from MGUS to active MM. In addition to the established “high-risk” MGUS/AMM features, we found that presence of MRI-FL at baseline, presence of CA and GEP70 scores >-0.26 carry a higher risk of PRO. Disclosures: Shaughnessy: Myeloma Health, Celgene, Genzyme, Novartis: Consultancy, Employment, Equity Ownership, Honoraria, Patents & Royalties. Barlogie:Celgene: Consultancy, Honoraria, Research Funding; IMF: Consultancy, Honoraria; MMRF: Consultancy; Millennium: Consultancy, Honoraria, Research Funding; Genzyme: Consultancy; Novartis: Research Funding; NCI: Research Funding; Johnson & Johnson: Research Funding; Centocor: Research Funding; Onyx: Research Funding; Icon: Research Funding.

scholarly journals Reassessment of the relationship between M-protein decrement and survival in multiple myeloma

1989 ◽  
Vol 59 (1) ◽  
pp. 110-112 ◽  
Author(s):  
M Palmer ◽  
A Belch ◽  
J Hanson ◽  
L Brox
Keyword(s):  
Multiple Myeloma ◽  
M Protein ◽  
The Relationship

Implications of rapidity of response to initial therapy in multiple myeloma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8606-8606
Author(s):  
Krishna Bilas Ghimire ◽  
Vincent Rajkumar ◽  
Angela Dispenzieri ◽  
Martha Lacy ◽  
Morie Gertz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Initial Therapy ◽  
M Protein ◽  
Newly Diagnosed ◽  
Long Term Outcomes ◽  
High Risk Disease ◽  
M Spike ◽  
The Relationship

8606 Background: The rapidity of response to initial therapy in multiple myeloma (MM) depends on a variety of factors. There is limited data on its implications on long term outcomes in patients (pts) with newly diagnosed MM. Methods: We retrospectively examined the outcomes in a cohort of 454 pts with newly diagnosed MM between Jan 2000- Dec 2011 undergoing induction therapy. Results: The median age at diagnosis was 66 yrs (29-92). Pts had measurable serum M-spike (>= 1 g/dL), dFLC (>=10 mg/dl) or 24 hour urinary M protein excretion (UrM; >=200 mg) in 70, 63 and 39% respectively. We first examined the relationship between the response to first cycle of therapy and overall survival (OS). We divided pts into quartiles based on their % reduction in the serum M spike, dFLC or UrM. The median OS (Table) was poorest for pts with the least reduction of serum M protein (P<0.001) and of dFLC. The cutoffs for Q1 was 25, 40and 40% decrease for serum M spike, dFLC and 24 hr UrM respectively. Among various baseline characteristics only higher age was predictive of a poor (Q1) response. Given the trend toward worse OS among the Q 4 group (maximum decrease in serum M spike), we examined the relationship to cytogenetic risk. Among 232 pts with FISH data available, proportion of pts with high-risk disease was 27, 12, 22 and 31% respectively in quartiles 1 - 4). In a multivariate analysis, quartile 1 and 4 of serum M-protein response and the high-risk FISH were independent risk factors associated inferior OS. Conclusions: Both shallow and very deep response to therapy in cycle 1 is a strong indicator of eventual disease outcome and should be considered as marker of high-risk disease, likely through different mechanisms. For the shallow responders, prospective trials should assess if a change in therapeutic management will alter the outcome of these pts. The rapid deep responders also appear represent a different high-risk biology, emphasizing the fact that pts with high-risk disease often have excellent initial responses, but poor long term outcomes. [Table: see text]

Diagnostic Imaging of Multiple Myeloma - FDG PET and MRI Complementary for Tracking Short Vs. Long Term Tumor Response.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 758-758 ◽  
Author(s):  
Ronald Walker ◽  
L. Jones-Jackson ◽  
Eric Rasmussen ◽  
M. Miceli ◽  
Elias Anaissie ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Fdg Pet ◽  
Axial Skeleton ◽  
Focal Lesions ◽  
Diffuse Infiltration ◽  
Extramedullary Tumor ◽  
Monitoring Treatment ◽  
Pet Scans ◽  
Serial Mri

Abstract Multiple myeloma results in both diffuse infiltration and/or focal lesions (FL) of the marrow. MRI detects FL long before X-ray. We routinely perform MRI of skull, entire spine, pelvis, sternum and shoulders. MRI-defined number of FL (#FL) is an adverse prognostic variable for both EFS and OS for patients treated according to Total Therapy 2, 2nd in importance only to cytogenetic abnormalities (CA) (univariate and Cox multivariate models using standard prognostic factors, CA, and #FL). Of these patients who also had FDG PET (PET), baseline analysis revealed the same axial skeleton FL as on MRI (r=0.47, p<0.001). Another 268 FL in long bones and 11 sites of extramedullary tumor were seen with PET due to MRI’s restricted field of view. Serial MRI and PET in 59 patients with FL on MRI (Fig. 1) and 123 patients with hyperintense MRI signal on STIR (no FL) revealed that patients without FL normalize MRI and PET scans synchronously with clinical (M-protein and bone marrow) response (nCR/CR) (Fig. 2a). However, in patients with FL, PET normalization follows nCR/CR very closely, while regression of MRI-FL (MRI-CR) lags in proportion to MRI #FL (Fig. 2b). We conclude PET is superior to MRI for detection of extent of disease and monitoring treatment response. However, PET-negative MRI-FL usually contain viable myeloma cells on biopsy which eventually progress. Thus, long term serial MRI is superior to PET in assessing completeness of response.

Rapid Response to Treatment of Multiple Myeloma Detected with FDG PET Scanning in Multiple Myeloma - Early Results from Total Therapy III.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 941-941
Author(s):  
Ronald Walker ◽  
L. Jones-Jackson ◽  
Eric Rasmussen ◽  
M. Miceli ◽  
Elias Anaissie ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Prognostic Significance ◽  
Pet Scan ◽  
M Protein ◽  
Response To Treatment ◽  
Focal Lesions ◽  
Early Results ◽  
Pet Scanning ◽  
Total Therapy

Abstract Fluorodeoxyglucose Positron Emission Tomography (PET) scanning can rapidly detect and quantify changes in tumor metabolism. We present early results from the first 47 patients enrolled in Total Therapy III for multiple myeloma using PET scanning and correlating with serum M protein. Since we have previously demonstrated that diffuse uptake patterns do not have prognostic significance, we have limited our assessment of these 47 patients to those with one or more PET-defined focal lesions (FL) at baseline who have had at least one follow-up PET scan (25 patients). Of this group of 25, 10 have had a second follow-up scan. These whole body PET scans were performed at baseline and at time points corresponding to immediately after two cycles of VDT-PACE, landmarks LMK1 and LMK2. Patients with complete resolution of FL on PET are considered to be in PET-CR. We find that 17/25 (68%) had a decrease in number of FL from baseline to LMK1 and 8/10 (80%) had a decrease in number of FL from baseline to LMK2. In addition, 6/25 (24%) were in PET-CR by LMK1 and 3/10 (30%) in PET-CR by LMK2. Similarly, a decrease in serum M-protein was seen in 16/25 (64%) from baseline to LMK1 and in 8/10 (80%) from baseline to LMK2. At baseline, 10 patients had serum M protein levels of 0.01 g/dl or less. Of these, 8 (80%) had PET-defined focal lesions, demonstrating PET’s ability to monitor tumor metabolism in the face of hypo- or non-secretory disease. Of these, 7 have been enrolled sufficient time to have a second PET scan, with 6/7 (86%) demonstrating a continuing decrease in number of FL in response to treatment. At baseline, PET detected 5 of 47 patients with extramedullary disease (EMD), a finding of severe adverse prognostic significance at baseline. Of these patients, all had FL at baseline PET and all had decreasing number of FL on first follow-up PET scan (two have had a second follow-up scan, one improving and one PET-CR). One of these patients with EMD is nonsecretory. From these data, we conclude that functional imaging with PET scanning offers important and unique information about early tumor response that improves patient management by demonstrating rapid change in response to treatment that not only parallels serum M-protein response but which also is reliable in hypo- or non-secretory disease as well as in detection and monitoring of extramedullary tumor, an ominous condition that is particularly difficult to detect in the hypo- or non-secretory patient.

scholarly journals Copy number signatures predict chromothripsis and clinical outcomes in newly diagnosed multiple myeloma

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kylee H. Maclachlan ◽  
Even H. Rustad ◽  
Andriy Derkach ◽  
Binbin Zheng-Lin ◽  
Venkata Yellapantula ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Copy Number ◽  
Prognostic Impact ◽  
Newly Diagnosed ◽  
Flexible Tool ◽  
Whole Exome ◽  
Hematological Cancers ◽  
Relationship Of ◽  
The Relationship ◽  
Validation Series

AbstractChromothripsis is detectable in 20–30% of newly diagnosed multiple myeloma (NDMM) patients and is emerging as a new independent adverse prognostic factor. In this study we interrogate 752 NDMM patients using whole genome sequencing (WGS) to investigate the relationship of copy number (CN) signatures to chromothripsis and show they are highly associated. CN signatures are highly predictive of the presence of chromothripsis (AUC = 0.90) and can be used identify its adverse prognostic impact. The ability of CN signatures to predict the presence of chromothripsis is confirmed in a validation series of WGS comprised of 235 hematological cancers (AUC = 0.97) and an independent series of 34 NDMM (AUC = 0.87). We show that CN signatures can also be derived from whole exome data (WES) and using 677 cases from the same series of NDMM, we are able to predict both the presence of chromothripsis (AUC = 0.82) and its adverse prognostic impact. CN signatures constitute a flexible tool to identify the presence of chromothripsis and is applicable to WES and WGS data.

scholarly journals 11C-acetate positron emission tomography is more precise than 18F-fluorodeoxyglucose positron emission tomography in evaluating tumor burden and predicting disease risk of multiple myeloma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Miao Chen ◽  
Wenjia Zhu ◽  
Jianhua Du ◽  
Chen Yang ◽  
Bing Han ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Disease Progression ◽  
Fdg Pet ◽  
Tumor Burden ◽  
Emission Tomography ◽  
Focal Lesions ◽  
Bone Marrow Uptake ◽  
Positron Emission

AbstractThe optimal method of tumor burden evaluation in newly diagnosed multiple myeloma (NDMM) is yet to be determined. This study aimed to compare the value of 11C-acetate positron-emission tomography (PET)/computed tomography (CT) (AC-PET and 18F-fluorodeoxyglucose PET/CT (FDG-PET) in the assessment of tumor burden in NDMM. This study evaluated 64 NDMM patients between February 2015 and July 2018. AC-PET and FDG-PET were used to assess myeloma lesions. The clinical data, imaging results, and their correlations were analyzed. Diffuse bone marrow uptake in AC-PET was significantly correlated with biomarkers for tumor burden, including serum hemoglobin (P = 0.020), M protein (P = 0.054), the percentage of bone marrow plasma cells (P < 0.001), and the Durie–Salmon stage of the disease (P = 0.007). The maximum standard uptake value (SUVmax) of focal lesions and high diffuse bone marrow uptake in AC-PET showed stronger correlations with high-risk disease (P = 0.017, P = 0.013) than those in FDG-PET. Moreover, the presence of diffuse bone marrow uptake, more than ten focal lesions, and an SUVmax of focal lesions of > 6.0 in AC-PET, but not in FDG-PET, predicted a higher probability of disease progression and shorter progression-free survival (P < 0.05). AC-PET outperformed FDG-PET in tumor burden evaluation and disease progression prediction in NDMM.

Real-World Experience with Minimal Residual Disease Testing with Next Generation Flow Cytometry and Functional Imaging in Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 17-18
Author(s):  
David Böckle ◽  
Paula Tabares Gaviria ◽  
Xiang Zhou ◽  
Janin Messerschmidt ◽  
Lukas Scheller ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Flow Cytometry ◽  
High Risk ◽  
Functional Imaging ◽  
Real World ◽  
Research Funding ◽  
Residual Disease ◽  
Focal Lesions ◽  
High Risk Disease ◽  
Minimal Residual

Background: Minimal residual disease (MRD) diagnostics in multiple myeloma (MM) are gaining increasing importance to determine response depth beyond complete remission (CR) since novel agents have shown to induce high rates of deep clinical responses. Moreover, recent reports indicated combining functional imaging with next generation flow cytometry (NGF) could be beneficial in predicting clinical outcome. This applies in particular to the subset of patients suffering from relapsed/refractory multiple myeloma (RRMM) who tend to show a higher incidence of residual focal lesions despite serological response. Here, we report our institutions experience with implementing both functional imaging and NGF-guided MRD diagnostics in clinical practice. Methods: Our study included patients with newly diagnosed multiple myeloma (NDMM) and RRMM achieving VGPR, CR or sCR. Bone marrow aspirates were obtained for MRD-testing according to IMWG 2016 criteria. Samples were collected between July 2019 and July 2020 and analyzed with NGF (according to EuroFlowTM guidelines) at a sensitivity level of 10-5. Results were compared to functional imaging obtained with positron emission tomography (PET) and diffusion-weighted magnetic resonance imaging (DW-MRI). High-risk disease was defined as presence of deletion 17p, translocation (14;16) or (4;14). Results: We included 66 patients with NDMM (n=39) and RRMM (n=27) who achieved VGPR or better. In patients with RRMM the median number of treatment lines was 2 (range 2-11). Fifteen patients suffered from high-risk disease. Median age at NGF diagnostics was 64 years (range 31-83). Among patients achieving VGPR (n=27), CR (n=10) and sCR (n=29) seventeen (26%) were MRD-negative by NGF testing. CR or better was significantly associated NGF MRD-negativity (p=0.04). Notably, rates of NGF MRD-negativity were similar among patients with NDMM (28%) and RRMM (26%). Even some heavily pretreated patients who underwent ≥ 4 lines of therapy achieved MRD-negativity on NGF (2 of 9). Functional imaging was performed in 46 (70%) patients with DW-MRI (n=22) and PET (n=26). Median time between NGF and imaging assessment was 2 days (range 0-147). Combining results from imaging and NGF, 12 out of 46 (26%) patients were MRD-negative with both methods (neg/neg). Three patients displayed disease activity as measured with both, imaging and NGF (pos/pos). Twenty-nine of the remaining patients were MRD-positive only according to NGF (pos/neg), while two patients were positive on imaging only (neg/pos). More patients demonstrated combined MRD-negativity on NGF and imaging (neg/neg) in the NDMM setting than in RRMM (32% versus 19%). We also observed that 30% of the patients with high-risk genetics showed MRD-negativity on both imaging and NGF. Of note, none of the patients with very advanced disease (≥4 previous lines) was MRD-negative on both techniques. Conclusion In the clinical routine, MRD diagnostics could be used to tailor maintenance and consolidation approaches for patients achieving deep responses by traditional IMWG criteria. Our real-world experience highlights that MRD-negativity can be achieved in patients suffering from high-risk disease and also in late treatment lines, supporting its value as endpoint for clinical trials. However, our data also support MRD diagnostics to be combined with functional imaging at least in the RRMM setting to rule out residual focal lesions. Future studies using MRD for clinical decision-making are highly warranted. Disclosures Einsele: Takeda: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; GlaxoSmithKline: Honoraria, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau. Rasche:Celgene/BMS: Honoraria; GlaxoSmithKline: Honoraria; Oncopeptides: Honoraria; Skyline Dx: Research Funding; Janssen: Honoraria; Sanofi: Honoraria.

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