Multiple Myeloma, Smoldering Multiple Myeloma, Monoclonal Gammopathy of Undetermined Significance
Conditions
Keywords
18-FDG PET/CT, Abnormal Plasma Cells, Serum Free Light-Chain Abnormality, Serum M-Protein, DCE-MRI, Multiple Myeloma, Smoldering Multiple Myeloma, SMM, MM
Brief summary
Background: \- Recent studies have shown that the premalignant conditions monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) have a high risk of progressing to multiple myeloma (MM). There are currently no known effective treatments to prevent MGUS or SMM from developing into MM, and there are no known tests for determining whether an individual with MGUS or SMM will develop MM. Researchers are investigating new and improved imaging techniques that may be able to better detect the progression of MGUS or SMM into MM. Objectives: * To compare the results of three imaging techniques in individuals with MGUS, SMM, and MM. * To correlate the information from the imaging studies with established clinical markers of progression from MGUS/SMM to MM. Eligibility: \- Individuals at least 18 years of age who have been diagnosed with monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, or multiple myeloma. Design: * Participants will be screened with a physical examination and medical history, and will provide baseline blood, urine, and bone marrow samples before beginning the imaging studies. * Participants will have three imaging studies on separate days: a standard 18-fludeoxyglucose positron emission tomography/computed tomography scan (18-FDG PET/CT), a PET/CT scan with an experimental sodium fluoride-based drug (18-NaF PET/CT), and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). * Participants will be closely monitored during each scan, and will provide additional blood samples before and after the scans. * Participants may provide additional blood, urine, tissue, and bone marrow samples for optional research studies.
Detailed description
Background: * Multiple myeloma (MM) is a plasma cell neoplasm with a median survival of 3-4 years. * Monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM) are premalignant plasma cell proliferative disorders characterized by elevated monoclonal protein and bone marrow plasma cells. MGUS affects 3.2% of Caucasians over the age of 50 and has a 1% annual risk of progression to MM. Approximately 3000 cases of SMM are diagnosed annually with a 10% annual risk of progression to MM. * Currently, it is not possible to predict which patients will progress to MM. * Novel imaging modalities (FDG-PET, 18-NaF PET and DCE-MRI) may improve our ability to predict patients who are at high risk of progression. Objectives: * To compare the results of imaging modalities (18-NaF PET/CT, 18-FDG PET/CT, and DCE-MRI) in patients with MGUS, SMM, and MM. * To correlate the imaging studies with established clinical markers of progression from MGUS/SMM to MM, including serum M-protein, percentage of plasma cells in the bone marrow, serum free light-chain abnormalities and immunoparesis, and ratio of normal/abnormal plasma cells in the bone marrow by flow cytometry. Eligibility: * A confirmed diagnosis of MGUS, SMM or MM (based on IMWG (International Myeloma Working Group) diagnostic criteria) * Age greater than or equal to 18 years * ECOG (Eastern Cooperative Oncology Group) performance status in the range of 0-2 Design: * This is a cross-sectional pilot study of patients with MGUS, SMM or MM. * Following initial evaluation and confirmation of diagnosis, baseline studies including skeletal survey will be done. * Subsequently 18-NaF PET/CT, 18-FDG PET/CT and DCE-MRI imaging will be done in all the patients. * 10 MGUS, 11 SMM and 10 MM patients will be enrolled on this protocol. * Patients may donate cellular products or tissues as appropriate for research purposes. * Almost all MGUS and SMM patients will be followed clinically as part of 10-C-0096: Natural History Study of Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Myeloma (SMM).
Interventions
DRUG18-NaF PET
The patient will receive 5mCi of F-18 NaF IV (intravenous) bolus, followed by a \~20 ml saline (sodium chloride IV infusion 0.9% w/v) flush over a period of \~20 seconds. Serial dynamic imaging (2 minutes/bed position) will be obtained over a 1-hour period. The patient will be permitted an imaging break until a static PET/CT is performed beginning at 2-hours post F-18 NaF injection.
OTHERDCE-MRI
An FDA (Food and Drug Administration) approved gadolinium chelate (e.g. Magnevist, Berlex Laboratories, NJ, USA) will be administered intravenously at 3 cc/sec using an automated pump injector (Medrad, Pittsburgh, PA, USA).
DRUG18-FDG PET/CT
The 18F-FDG injection procedure will be injected and be followed by a \~20 ml saline (sodium chloride IV infusion 0.9% w/v) flush over a period of \~20 seconds. The injection site will be evaluated pre- and post administration for any reaction (e.g. bleeding, hematoma, redness, or infection). Whole body (vertex to toes) static PET/CT imaging will be performed beginning at 1-hour, and again at 2-hours post injection.
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* INCLUSION CRITERIA: * Diagnosis of MGUS, SMM and MM will be made in accordance with the clinical diagnostic criteria set forth by the International Myeloma Working Group.2. The diagnoses will be confirmed by laboratory tests, serum/urine protein electrophoresis, immunofixation and light-chain assays, a skeletal survey, or immunohistochemistry analyses of the bone marrow biopsy, or a combination of these. * Age greater than or equal to 18 years. * ECOG (Eastern Cooperative Oncology Group) performance status of 0-2. * The patient must be competent to sign an informed consent form. * Creatinine less than 2.5 ULN or eGFR (estimated glomerular filtration rate) greater than 30
Exclusion criteria
* A medical history of other malignancy (apart from basal cell carcinoma of the skin or in situ cervical carcinoma; also, for MM patients this does not include MM) except if the patient has been free of symptoms and without active therapy during at least the previous 5 years. * Female subject is pregnant or breast-feeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Count of Participants With Positive and Negative 18F-FDG PET CT and F18-NaF PET CT Imaging Results in Individuals With MGUS, SMM, and MM. | 60 days | 18F-FDG PET CT and F18-NaF PET CT imaging results were compared in participants with MGUS, SMM, and MM. Lesions were considered positive if focal uptake corresponded to lesions identified on CT for NaF and negative if no uptake seen in lesions. Criteria to define FDG positivity included parameters published by Zamagni et al with focal abnormal uptake more intense than background. |
| Count of Participants With Positive DCE-MRI Imaging Results | 60 days | DCE-MRI, an FDA approved gadolinium chelate (e.g. Magnevist, Berlex Laboratories, NJ, USA) will be administered intravenously at 3 cc/sec using an automated pump injector (Medrad, Pittsburgh, PA, USA). The criteria was presence of early and diffuse hyper-enhancement compared to the surrounding bone marrow. The pattern of marrow involvement on MRI was characterized as: (1) normal when there was no evidence of abnormal signal intensity; (2) focal, which consisted of localized areas of abnormal marrow; the lesions are darker than yellow marrow and slightly darker than or isointense to red marrow on T1-weights images; (3) diffuse, in which normal bone marrow signal intensity is completely absent, the intervertebral disks appear brighter than or isointense to the diseased marrow; and finally (4) heterogeneous that consists of innumerable small foci of disease on a background of intact marrow, with small dark lesions on T1-weighted images, which become bright on T2-weighted image. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of Serum Angiogenic Markers Ang2 (Angiopoietin), G-CSF (Granulocyte-colony Stimulating Factor), Follistatin, HGF (Hepatocyte Growth Factor), FGF-1, Endothelin 1, and VEGF-A (Vascular Endothelial Growth Factor-A) Between MGUS and SMM/MM Groups | 60 days | The assay was performed according to the manufacture's protocol, and all samples were diluted 1:3. Cytokine values were calculated using a five-parameter standard curve with Bio-Plex Manager 6.1. |
| Comparison of Microvessel Density (MVD) Among Patients With MGUS, SMM, and MM | 60 days | Microvessel density was estimated by determining the average number of cluster of differentiation 34 (CD34)-stained microvessels in 10 areas of maximal MVD counted at a high-power field (h.p.f. x 500 magnification). Large vessels and vessels in the periosteum on bone were excluded. Areas of staining with no discrete breaks were counted as a single vessel. The presence of a lumen was not required. |
| Comparison of Reverse Contrast Transfer Rate (Kep) and Forward Contrast Transfer Rate (Ktrans) Among Patients With MGUS, SMM, and MM | 60 days | Pharmacokinetic parameters Kep and Ktrans were measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). |
| Comparison of Serum Angiogenic Marker Reverse Contrast Transfer Rate (Kep) Between MGUS and SMM/MM Groups | 60 days | Pharmacokinetic parameter Kep was measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). |
| Comparison of Microvessel Density (MVD) Between MGUS and SMM/MM Groups | 60 days | Microvessel density was estimated by determining the average number of CD34-stained microvessels in 10 areas of maximal MVD counted at a high-power field (h.p.f. x 500 magnification). |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORPeter L Choyke, M.D.
National Cancer Institute (NCI)
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Imaging in MGUS, SMM, and MM Participants will have three imaging studies on separate days: a standard positron emission tomography/computed tomography scan (18-FDG PET/CT), a PET/CT scan with an experimental sodium fluoride-based drug (18-NaF PET/CT), and magnetic resonance imaging (DCE-MRI).
18-NaF PET: The patient will patient will receive 5mCi of F-18 NaF IV bolus, followed by a \
20 ml saline (sodium chloride IV infusion 0.9% w/v) flush over a period of \
20 seconds. Serial dynamic imaging (2 minutes/bed position) will be obtained over a 1-hour period. The patient will be permitted an imaging break until a static PET/CT is performed beginning at 2-hours post F-18 NaF injection. DCE-MRI: An FDA approved gadolinium chelate (e.g. Magnevist, Berlex Laboratories, NJ, USA) will be administered intravenously at 3 cc/sec using an automated pump injector (Medrad, Pittsburgh, PA, USA).18-FDG PET/CT: The 18F-FDG injection procedure will be injected and be followed by a \
20 ml saline flush over a period of \
20 sec. | 31 |
| Total | 31 |
Baseline characteristics
| Characteristic | Imaging in MGUS, SMM, and MM |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 11 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants |
| Age, Continuous | 62.89 years STANDARD_DEVIATION 10.58 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 26 Participants |
| Region of Enrollment United States | 31 Participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 31 |
| other Total, other adverse events | 0 / 31 |
| serious Total, serious adverse events | 0 / 31 |
Outcome results
Primary
Count of Participants With Positive and Negative 18F-FDG PET CT and F18-NaF PET CT Imaging Results in Individuals With MGUS, SMM, and MM.
18F-FDG PET CT and F18-NaF PET CT imaging results were compared in participants with MGUS, SMM, and MM. Lesions were considered positive if focal uptake corresponded to lesions identified on CT for NaF and negative if no uptake seen in lesions. Criteria to define FDG positivity included parameters published by Zamagni et al with focal abnormal uptake more intense than background.
Time frame: 60 days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MGUS (Monoclonal Gammopathy of Undetermined Significance) | Count of Participants With Positive and Negative 18F-FDG PET CT and F18-NaF PET CT Imaging Results in Individuals With MGUS, SMM, and MM. | Negative 18F-FDG PET CT result | 10 Participants |
| MGUS (Monoclonal Gammopathy of Undetermined Significance) | Count of Participants With Positive and Negative 18F-FDG PET CT and F18-NaF PET CT Imaging Results in Individuals With MGUS, SMM, and MM. | Negative F18-NaF PET CT result | 10 Participants |
| MGUS (Monoclonal Gammopathy of Undetermined Significance) | Count of Participants With Positive and Negative 18F-FDG PET CT and F18-NaF PET CT Imaging Results in Individuals With MGUS, SMM, and MM. | Positive F18-NaF PET CT result | 0 Participants |
| MGUS (Monoclonal Gammopathy of Undetermined Significance) | Count of Participants With Positive and Negative 18F-FDG PET CT and F18-NaF PET CT Imaging Results in Individuals With MGUS, SMM, and MM. | Positive 18F-FDG PET CT result | 0 Participants |
| SMM (Smoldering Multiple Myeloma) | Count of Participants With Positive and Negative 18F-FDG PET CT and F18-NaF PET CT Imaging Results in Individuals With MGUS, SMM, and MM. | Positive F18-NaF PET CT result | 0 Participants |
| SMM (Smoldering Multiple Myeloma) | Count of Participants With Positive and Negative 18F-FDG PET CT and F18-NaF PET CT Imaging Results in Individuals With MGUS, SMM, and MM. | Negative F18-NaF PET CT result | 10 Participants |
| SMM (Smoldering Multiple Myeloma) | Count of Participants With Positive and Negative 18F-FDG PET CT and F18-NaF PET CT Imaging Results in Individuals With MGUS, SMM, and MM. | Negative 18F-FDG PET CT result | 9 Participants |
| SMM (Smoldering Multiple Myeloma) | Count of Participants With Positive and Negative 18F-FDG PET CT and F18-NaF PET CT Imaging Results in Individuals With MGUS, SMM, and MM. | Positive 18F-FDG PET CT result | 1 Participants |
| MM (Multiple Myeloma) | Count of Participants With Positive and Negative 18F-FDG PET CT and F18-NaF PET CT Imaging Results in Individuals With MGUS, SMM, and MM. | Negative F18-NaF PET CT result | 1 Participants |
| MM (Multiple Myeloma) | Count of Participants With Positive and Negative 18F-FDG PET CT and F18-NaF PET CT Imaging Results in Individuals With MGUS, SMM, and MM. | Positive 18F-FDG PET CT result | 5 Participants |
| MM (Multiple Myeloma) | Count of Participants With Positive and Negative 18F-FDG PET CT and F18-NaF PET CT Imaging Results in Individuals With MGUS, SMM, and MM. | Positive F18-NaF PET CT result | 9 Participants |
| MM (Multiple Myeloma) | Count of Participants With Positive and Negative 18F-FDG PET CT and F18-NaF PET CT Imaging Results in Individuals With MGUS, SMM, and MM. | Negative 18F-FDG PET CT result | 5 Participants |
Primary
Count of Participants With Positive DCE-MRI Imaging Results
DCE-MRI, an FDA approved gadolinium chelate (e.g. Magnevist, Berlex Laboratories, NJ, USA) will be administered intravenously at 3 cc/sec using an automated pump injector (Medrad, Pittsburgh, PA, USA). The criteria was presence of early and diffuse hyper-enhancement compared to the surrounding bone marrow. The pattern of marrow involvement on MRI was characterized as: (1) normal when there was no evidence of abnormal signal intensity; (2) focal, which consisted of localized areas of abnormal marrow; the lesions are darker than yellow marrow and slightly darker than or isointense to red marrow on T1-weights images; (3) diffuse, in which normal bone marrow signal intensity is completely absent, the intervertebral disks appear brighter than or isointense to the diseased marrow; and finally (4) heterogeneous that consists of innumerable small foci of disease on a background of intact marrow, with small dark lesions on T1-weighted images, which become bright on T2-weighted image.
Time frame: 60 days
Population: Missing means the imaging test was not done. Unclear means it is indeterminate whether an imaging result is positive or negative.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MGUS (Monoclonal Gammopathy of Undetermined Significance) | Count of Participants With Positive DCE-MRI Imaging Results | Negative | 9 Participants |
| MGUS (Monoclonal Gammopathy of Undetermined Significance) | Count of Participants With Positive DCE-MRI Imaging Results | Missing | 0 Participants |
| MGUS (Monoclonal Gammopathy of Undetermined Significance) | Count of Participants With Positive DCE-MRI Imaging Results | Positive | 1 Participants |
| MGUS (Monoclonal Gammopathy of Undetermined Significance) | Count of Participants With Positive DCE-MRI Imaging Results | Unclear | 0 Participants |
| SMM (Smoldering Multiple Myeloma) | Count of Participants With Positive DCE-MRI Imaging Results | Positive | 1 Participants |
| SMM (Smoldering Multiple Myeloma) | Count of Participants With Positive DCE-MRI Imaging Results | Negative | 9 Participants |
| SMM (Smoldering Multiple Myeloma) | Count of Participants With Positive DCE-MRI Imaging Results | Missing | 0 Participants |
| SMM (Smoldering Multiple Myeloma) | Count of Participants With Positive DCE-MRI Imaging Results | Unclear | 0 Participants |
| MM (Multiple Myeloma) | Count of Participants With Positive DCE-MRI Imaging Results | Missing | 1 Participants |
| MM (Multiple Myeloma) | Count of Participants With Positive DCE-MRI Imaging Results | Positive | 9 Participants |
| MM (Multiple Myeloma) | Count of Participants With Positive DCE-MRI Imaging Results | Negative | 0 Participants |
| MM (Multiple Myeloma) | Count of Participants With Positive DCE-MRI Imaging Results | Unclear | 0 Participants |
Secondary
Comparison of Microvessel Density (MVD) Among Patients With MGUS, SMM, and MM
Microvessel density was estimated by determining the average number of cluster of differentiation 34 (CD34)-stained microvessels in 10 areas of maximal MVD counted at a high-power field (h.p.f. x 500 magnification). Large vessels and vessels in the periosteum on bone were excluded. Areas of staining with no discrete breaks were counted as a single vessel. The presence of a lumen was not required.
Time frame: 60 days
Population: Three patients with MM did not undergo bone marrow biopsies and were not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MGUS (Monoclonal Gammopathy of Undetermined Significance) | Comparison of Microvessel Density (MVD) Among Patients With MGUS, SMM, and MM | 15 microvessels/hpf |
| SMM (Smoldering Multiple Myeloma) | Comparison of Microvessel Density (MVD) Among Patients With MGUS, SMM, and MM | 19.4 microvessels/hpf |
| MM (Multiple Myeloma) | Comparison of Microvessel Density (MVD) Among Patients With MGUS, SMM, and MM | 20.9 microvessels/hpf |
p-value: 0.008Jonckheere-Terpstra test for trend
Secondary
Comparison of Microvessel Density (MVD) Between MGUS and SMM/MM Groups
Microvessel density was estimated by determining the average number of CD34-stained microvessels in 10 areas of maximal MVD counted at a high-power field (h.p.f. x 500 magnification).
Time frame: 60 days
Population: Serum was not available for three patients in the SMM group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MGUS (Monoclonal Gammopathy of Undetermined Significance) | Comparison of Microvessel Density (MVD) Between MGUS and SMM/MM Groups | 15.04 microvessels/hpf | Standard Error 1.14 |
| SMM (Smoldering Multiple Myeloma) | Comparison of Microvessel Density (MVD) Between MGUS and SMM/MM Groups | 21.64 microvessels/hpf | Standard Error 1.9 |
p-value: 0.011Wilcoxon rank sum test
Secondary
Comparison of Reverse Contrast Transfer Rate (Kep) and Forward Contrast Transfer Rate (Ktrans) Among Patients With MGUS, SMM, and MM
Pharmacokinetic parameters Kep and Ktrans were measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).
Time frame: 60 days
Population: Three patients with MM did not undergo bone marrow biopsies and were not included in this analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| MGUS (Monoclonal Gammopathy of Undetermined Significance) | Comparison of Reverse Contrast Transfer Rate (Kep) and Forward Contrast Transfer Rate (Ktrans) Among Patients With MGUS, SMM, and MM | Kep | 3.9 per min |
| MGUS (Monoclonal Gammopathy of Undetermined Significance) | Comparison of Reverse Contrast Transfer Rate (Kep) and Forward Contrast Transfer Rate (Ktrans) Among Patients With MGUS, SMM, and MM | Ktrans | 2.4 per min |
| SMM (Smoldering Multiple Myeloma) | Comparison of Reverse Contrast Transfer Rate (Kep) and Forward Contrast Transfer Rate (Ktrans) Among Patients With MGUS, SMM, and MM | Kep | 9 per min |
| SMM (Smoldering Multiple Myeloma) | Comparison of Reverse Contrast Transfer Rate (Kep) and Forward Contrast Transfer Rate (Ktrans) Among Patients With MGUS, SMM, and MM | Ktrans | 2.3 per min |
| MM (Multiple Myeloma) | Comparison of Reverse Contrast Transfer Rate (Kep) and Forward Contrast Transfer Rate (Ktrans) Among Patients With MGUS, SMM, and MM | Kep | 5.8 per min |
| MM (Multiple Myeloma) | Comparison of Reverse Contrast Transfer Rate (Kep) and Forward Contrast Transfer Rate (Ktrans) Among Patients With MGUS, SMM, and MM | Ktrans | 3.1 per min |
p-value: 0.15Jonckheere-Terpstra test for trend
p-value: 0.33Jonckheere-Terpstra test for trend
Secondary
Comparison of Serum Angiogenic Marker Reverse Contrast Transfer Rate (Kep) Between MGUS and SMM/MM Groups
Pharmacokinetic parameter Kep was measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).
Time frame: 60 days
Population: Serum was not available for three patients in the SMM group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MGUS (Monoclonal Gammopathy of Undetermined Significance) | Comparison of Serum Angiogenic Marker Reverse Contrast Transfer Rate (Kep) Between MGUS and SMM/MM Groups | 4.05 per min | Standard Error 0.73 |
| SMM (Smoldering Multiple Myeloma) | Comparison of Serum Angiogenic Marker Reverse Contrast Transfer Rate (Kep) Between MGUS and SMM/MM Groups | 6.93 per min | Standard Error 0.97 |
p-value: 0.08Wilcoxon rank sum test
Secondary
Comparison of Serum Angiogenic Markers Ang2 (Angiopoietin), G-CSF (Granulocyte-colony Stimulating Factor), Follistatin, HGF (Hepatocyte Growth Factor), FGF-1, Endothelin 1, and VEGF-A (Vascular Endothelial Growth Factor-A) Between MGUS and SMM/MM Groups
The assay was performed according to the manufacture's protocol, and all samples were diluted 1:3. Cytokine values were calculated using a five-parameter standard curve with Bio-Plex Manager 6.1.
Time frame: 60 days
Population: Serum was not available for three patients in the SMM group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MGUS (Monoclonal Gammopathy of Undetermined Significance) | Comparison of Serum Angiogenic Markers Ang2 (Angiopoietin), G-CSF (Granulocyte-colony Stimulating Factor), Follistatin, HGF (Hepatocyte Growth Factor), FGF-1, Endothelin 1, and VEGF-A (Vascular Endothelial Growth Factor-A) Between MGUS and SMM/MM Groups | VEGF-A (vascular endothelial growth factor-A) | 844.31 pg/ml | Standard Error 435.94 |
| MGUS (Monoclonal Gammopathy of Undetermined Significance) | Comparison of Serum Angiogenic Markers Ang2 (Angiopoietin), G-CSF (Granulocyte-colony Stimulating Factor), Follistatin, HGF (Hepatocyte Growth Factor), FGF-1, Endothelin 1, and VEGF-A (Vascular Endothelial Growth Factor-A) Between MGUS and SMM/MM Groups | G-CSF (granulocyte-colony stimulating factor) | 24.92 pg/ml | Standard Error 11.66 |
| MGUS (Monoclonal Gammopathy of Undetermined Significance) | Comparison of Serum Angiogenic Markers Ang2 (Angiopoietin), G-CSF (Granulocyte-colony Stimulating Factor), Follistatin, HGF (Hepatocyte Growth Factor), FGF-1, Endothelin 1, and VEGF-A (Vascular Endothelial Growth Factor-A) Between MGUS and SMM/MM Groups | FGF-1 (fibroblast growth factor 1) | NA pg/ml | — |
| MGUS (Monoclonal Gammopathy of Undetermined Significance) | Comparison of Serum Angiogenic Markers Ang2 (Angiopoietin), G-CSF (Granulocyte-colony Stimulating Factor), Follistatin, HGF (Hepatocyte Growth Factor), FGF-1, Endothelin 1, and VEGF-A (Vascular Endothelial Growth Factor-A) Between MGUS and SMM/MM Groups | Follistatin | 562.45 pg/ml | Standard Error 88.89 |
| MGUS (Monoclonal Gammopathy of Undetermined Significance) | Comparison of Serum Angiogenic Markers Ang2 (Angiopoietin), G-CSF (Granulocyte-colony Stimulating Factor), Follistatin, HGF (Hepatocyte Growth Factor), FGF-1, Endothelin 1, and VEGF-A (Vascular Endothelial Growth Factor-A) Between MGUS and SMM/MM Groups | Ang2 (angiopoietin) | 2465.97 pg/ml | Standard Error 589.27 |
| MGUS (Monoclonal Gammopathy of Undetermined Significance) | Comparison of Serum Angiogenic Markers Ang2 (Angiopoietin), G-CSF (Granulocyte-colony Stimulating Factor), Follistatin, HGF (Hepatocyte Growth Factor), FGF-1, Endothelin 1, and VEGF-A (Vascular Endothelial Growth Factor-A) Between MGUS and SMM/MM Groups | HGF (hepatocyte growth factor) | 390.57 pg/ml | Standard Error 70.82 |
| MGUS (Monoclonal Gammopathy of Undetermined Significance) | Comparison of Serum Angiogenic Markers Ang2 (Angiopoietin), G-CSF (Granulocyte-colony Stimulating Factor), Follistatin, HGF (Hepatocyte Growth Factor), FGF-1, Endothelin 1, and VEGF-A (Vascular Endothelial Growth Factor-A) Between MGUS and SMM/MM Groups | Endothelin 1 | NA pg/ml | — |
| SMM (Smoldering Multiple Myeloma) | Comparison of Serum Angiogenic Markers Ang2 (Angiopoietin), G-CSF (Granulocyte-colony Stimulating Factor), Follistatin, HGF (Hepatocyte Growth Factor), FGF-1, Endothelin 1, and VEGF-A (Vascular Endothelial Growth Factor-A) Between MGUS and SMM/MM Groups | Ang2 (angiopoietin) | 3804.42 pg/ml | Standard Error 467.16 |
| SMM (Smoldering Multiple Myeloma) | Comparison of Serum Angiogenic Markers Ang2 (Angiopoietin), G-CSF (Granulocyte-colony Stimulating Factor), Follistatin, HGF (Hepatocyte Growth Factor), FGF-1, Endothelin 1, and VEGF-A (Vascular Endothelial Growth Factor-A) Between MGUS and SMM/MM Groups | VEGF-A (vascular endothelial growth factor-A) | 1301.52 pg/ml | Standard Error 196.47 |
| SMM (Smoldering Multiple Myeloma) | Comparison of Serum Angiogenic Markers Ang2 (Angiopoietin), G-CSF (Granulocyte-colony Stimulating Factor), Follistatin, HGF (Hepatocyte Growth Factor), FGF-1, Endothelin 1, and VEGF-A (Vascular Endothelial Growth Factor-A) Between MGUS and SMM/MM Groups | FGF-1 (fibroblast growth factor 1) | NA pg/ml | — |
| SMM (Smoldering Multiple Myeloma) | Comparison of Serum Angiogenic Markers Ang2 (Angiopoietin), G-CSF (Granulocyte-colony Stimulating Factor), Follistatin, HGF (Hepatocyte Growth Factor), FGF-1, Endothelin 1, and VEGF-A (Vascular Endothelial Growth Factor-A) Between MGUS and SMM/MM Groups | Endothelin 1 | NA pg/ml | — |
| SMM (Smoldering Multiple Myeloma) | Comparison of Serum Angiogenic Markers Ang2 (Angiopoietin), G-CSF (Granulocyte-colony Stimulating Factor), Follistatin, HGF (Hepatocyte Growth Factor), FGF-1, Endothelin 1, and VEGF-A (Vascular Endothelial Growth Factor-A) Between MGUS and SMM/MM Groups | HGF (hepatocyte growth factor) | 654.34 pg/ml | Standard Error 57.97 |
| SMM (Smoldering Multiple Myeloma) | Comparison of Serum Angiogenic Markers Ang2 (Angiopoietin), G-CSF (Granulocyte-colony Stimulating Factor), Follistatin, HGF (Hepatocyte Growth Factor), FGF-1, Endothelin 1, and VEGF-A (Vascular Endothelial Growth Factor-A) Between MGUS and SMM/MM Groups | G-CSF (granulocyte-colony stimulating factor) | 101.08 pg/ml | Standard Error 42.81 |
| SMM (Smoldering Multiple Myeloma) | Comparison of Serum Angiogenic Markers Ang2 (Angiopoietin), G-CSF (Granulocyte-colony Stimulating Factor), Follistatin, HGF (Hepatocyte Growth Factor), FGF-1, Endothelin 1, and VEGF-A (Vascular Endothelial Growth Factor-A) Between MGUS and SMM/MM Groups | Follistatin | 823.15 pg/ml | Standard Error 83 |
p-value: 0.024Wilcoxon rank sum test
p-value: 0.055Wilcoxon rank sum test
p-value: 0.055Wilcoxon rank sum test
p-value: 0.0098Wilcoxon rank sum test
p-value: 0.02Wilcoxon rank sum test