An observational study in Myeloma, Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smouldering Myeloma, sponsored by Oxford University Hospitals NHS Trust. Completed at 1 site in United Kingdom. Open to participants aged 18 Years to 99 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-08-19.
Sponsored by Oxford University Hospitals NHS Trust · Observational
In the proposed study, the investigators will aim to develop and pilot a Magnetic Resonance (MR) imaging protocol and assess its ability to achieve the following: quantification of tumour burden and bone loss, detecting longitudinal changes in tumour load with therapy and detecting longitudinal changes in microarchitecture with therapy. The investigators also aim to investigate whether bone loss is better, worse or the same with different imaging techniques. This will be investigated by correlating the DXA imaging data with Diffusion-Weighted Magnetic Resonance Imaging (DWMRI) to see if it is possible to achieve quantifiable data of bone density.
In the proposed study, the investigators will aim to develop and pilot a Magnetic Resonance (MR) imaging protocol and assess its ability to achieve the following: quantification of tumour burden and bone loss, detecting longitudinal changes in tumour load with therapy and detecting longitudinal changes in microarchitecture with therapy. The investigators also aim to investigate whether bone loss is better, worse or the same with different imaging techniques. This will be investigated by correlating the DXA imaging data with Diffusion-Weighted Magnetic Resonance Imaging (DWMRI) to see if it is possible to achieve quantifiable data of bone density.
Using the expertise of the Oxford Centre For Clinical Magnetic Resonance Research (OCMR) for imaging protocol development, and the new Fine Structural Analysis (FSA, Osteotronix Ltd, formerly Acuitas Medical) bone density quantification MRI method (Rafferty et al 2016), the investigators will test a single protocol which combines three emerging experimental imaging sequences into a simple, non-invasive whole body imaging protocol to quantify disease burden and bone disease. This has never been done before; if shown to be feasible, such a method would have two important applications: to precisely guide commissioned therapies in the clinic, so improving patient management; and as an exciting, novel research tool for the longitudinal combined assessment of tumour burden and cancer-induced bone disease in response to therapy.
The investigators hypothesize that this imaging tool will be superior to the combined current standard-of-care investigations in the quantification of tumour burden and bone loss. There are currently no tools available for quantifying structural changes to bone and overall bone loss in myeloma.
2,306 studies on the registry are indexed under Neoplasms, Plasma Cell; 246 are open to participants now.
This study's enrollment of 67 is below the median of 150 across 265 observational studies indexed under Neoplasms, Plasma Cell.
Browse Neoplasms, Plasma Cell studies →Oxford University Hospitals NHS Trust is the lead sponsor of 92 studies on the registry; 7 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Participants in Groups 1 \& 2 will be recruited via the Haematology Outpatients clinic in Churchill Hospital.
Group 3 participants will be recruited from the community
Inclusion Criteria (All Groups):
Inclusion Criteria (Groups 1 and 2):
Exclusion Criteria (All Groups):
Exclusion Criteria (Groups 1 and 2):
Participants will be recruited at the point of either diagnosis or relapse. Any standard investigations that the clinician deems necessary will be carried out. Following recruitment, participants will undergo the first study appointment, the experimental combined MR imaging protocol, the DXA imaging scan and the bone biomarker blood and urine tests. This will be repeated at 6 months.
Other: Diffusion Weighted Magnetic Resonance Imaging (DWMRI) · Other: DXA scan · Other: Bloods and urine
Participants will be recruited at the point of either diagnosis or relapse. Any standard investigations that the clinician deems necessary will be carried out. Following recruitment, participants will undergo the first study appointment, the experimental combined MR imaging protocol, the DXA imaging scan and the bone biomarker blood and urine tests. This will be repeated at 6 months.
Other: Diffusion Weighted Magnetic Resonance Imaging (DWMRI) · Other: DXA scan · Other: Bloods and urine
Participants will have the experimental combined MR imaging.
Other: Diffusion Weighted Magnetic Resonance Imaging (DWMRI)
Using the expertise of the Oxford Centre For Clinical Magnetic Resonance Research (OCMR) for imaging protocol development, and the new Fine Structural Analysis (FSA, Osteotronix Ltd, formerly Acuitas Medical) bone density quantification MRI method (Rafferty et al 2016), we will test a single protocol which combines three emerging experimental imaging sequences into a simple, non-invasive whole body imaging protocol to quantify disease burden and bone disease. To our knowledge, this has never been done before; if shown to be feasible, such a method would have two important applications: to precisely guide commissioned therapies in the clinic, so improving patient management; and as an exciting, novel research tool for the longitudinal combined assessment of tumour burden and cancer-induced bone disease in response to therapy.
Used to assess bone density
Samples will be taken to assess bone biomarkers
Primary Outcome 1: Quantifying Tumour Burden [Correlations With Apparent Diffusion Coefficient (ADC) Measurements]
Primary Objective 1: To assess whether the novel magnetic resonance (MR) protocol and exploratory bone biomarkers can improve quantification of tumour burden in patients with new or relapsed myeloma at baseline assessment, compared to paraprotein levels alone. This particular section analysed the correlation between the Apparent Diffusion Coefficient (ADC) measurements (from the Diffusion Weighted Magnetic Resonance Imaging (DW-MRI) component of the sequences) of lytic bone lesions, with standard clinical correlates of tumour burden (serum paraprotein, and serum paraprotein-associated immunoglobulin level). The measurement of ADC from DW-MRI is further described by Messiou et. al. \[1\] \[1\] Messiou, Christina, et al. "Guidelines for acquisition, interpretation, and reporting of whole-body MRI in myeloma: myeloma response assessment and diagnosis system (MY-RADS)." Radiology 291.1 (2019): 5-13.
Time frame: At baseline
Primary Outcome 1: Quantifying Tumour Burden [Correlations With Myeloma Response Assessment and Diagnosis System (MY-RADS) Pattern of Disease]
Primary Objective 1: To assess whether the novel MR protocol and exploratory bone biomarkers can improve quantification of tumour burden in patients with new or relapsed myeloma at baseline assessment, compared to paraprotein levels alone. Participants' baseline novel MR scan was analysed by an expert radiologist, and pattern of disease was qualitatively classified using the MY-RADS (Myeloma Response Assessment and Diagnosis System) imaging recommendations, described in Figure 2 by Messiou et. al. \[1\]. This particular section analysed whether standard clinical correlate of tumour burden (serum paraprotein) differed by radiological pattern of disease (e.g., normal, focal, diffuse). \[1\] Messiou, Christina, et al. "Guidelines for acquisition, interpretation, and reporting of whole-body MRI in myeloma: myeloma response assessment and diagnosis system (MY-RADS)." Radiology 291.1 (2019): 5-13.
Time frame: At baseline
Primary Outcome 1: Quantifying Tumour Burden (Correlations With Bone Turnover Markers)
Primary Objective 1: To assess whether the novel Magnetic Resonance (MR) protocol and exploratory bone biomarkers can improve quantification of tumour burden in patients with new or relapsed myeloma at baseline assessment, compared to paraprotein levels alone. This section examined correlation between baseline bone biomarkers and baseline serum paraprotein in a pooled cohort of patients from Groups 1 and 2, using Spearman's Rank Correlation Coefficients.
Time frame: At baseline
Primary Outcome 2: Quantifying Bone Loss - Inter-Group Differences in Baseline Serum P1NP (Procollagen Type 1 N-terminal Propeptide)
Primary Outcome 2: To assess whether the novel magnetic resonance (MR) protocol and exploratory bone turnover markers can improve quantification of bone loss in patients with myeloma (new, relapsed, smouldering) and Monoclonal Gammopathy Of Uncertain Significance (MGUS) at baseline assessment, compared to Dual-energy X-ray Absorptiometry (DXA) and established bone turnover markers alone. This particular section analysed the inter-group difference in baseline serum P1NP (Procollagen Type 1 N-terminal Propeptide) bone turnover marker levels, in patients from Groups 1a (new myeloma), 1b (relapsed myeloma), 1c (smouldering myeloma) and 2 (MGUS).
Time frame: At baseline
Primary Outcome 2: Quantifying Bone Loss - Inter-Group Differences in Baseline Serum CTX-1 (Collagen Cross-Linked C-Telopeptide Type I)
Primary Outcome 2: To assess whether the novel magnetic resonance (MR) protocol and exploratory bone turnover markers can improve quantification of bone loss in patients with myeloma (new, relapsed, smouldering) and Monoclonal Gammopathy Of Uncertain Significance (MGUS) at baseline assessment, compared to Dual-energy X-ray Absorptiometry (DXA) and established bone turnover markers alone. This particular section analysed the inter-group difference in baseline serum CTX-1 (Collagen Cross-Linked C-Telopeptide Type I) bone turnover marker levels, in patients from Groups 1a (new myeloma), 1b (relapsed myeloma), 1c (smouldering myeloma) and 2 (MGUS).
Time frame: At baseline
Primary Outcome 2: Quantifying Bone Loss - Inter-Group Differences in Baseline Serum ALP (Alkaline Phosphatase)
Primary Outcome 2: To assess whether the novel magnetic resonance (MR) protocol and exploratory bone turnover markers can improve quantification of bone loss in patients with myeloma (new, relapsed, smouldering) and Monoclonal Gammopathy Of Uncertain Significance (MGUS) at baseline assessment, compared to Dual-energy X-ray Absorptiometry (DXA) and established bone turnover markers alone. This particular section analysed the inter-group difference in baseline serum ALP (Alkaline Phosphatase) bone turnover marker levels, in patients from Groups 1a (new myeloma), 1b (relapsed myeloma), 1c (smouldering myeloma) and 2 (MGUS).
Time frame: At baseline
Primary Outcome 2: Quantifying Bone Loss - Inter-Group Differences in Baseline Serum DKK1 (Dickkopf WNT Signaling Pathway Inhibitor 1)
Primary Outcome 2: To assess whether the novel magnetic resonance (MR) protocol and exploratory bone turnover markers can improve quantification of bone loss in patients with myeloma (new, relapsed, smouldering) and Monoclonal Gammopathy Of Uncertain Significance (MGUS) at baseline assessment, compared to Dual-energy X-ray Absorptiometry (DXA) and established bone turnover markers alone. This particular section analysed the inter-group difference in baseline serum DKK1 (Dickkopf WNT Signaling Pathway Inhibitor 1) bone turnover marker levels, in patients from Groups 1a (new myeloma), 1b (relapsed myeloma), 1c (smouldering myeloma) and 2 (MGUS).
Time frame: At baseline
Primary Outcome 2: Quantifying Bone Loss - Inter-Group Differences in Baseline Serum Sclerostin
Primary Outcome 2: To assess whether the novel magnetic resonance (MR) protocol and exploratory bone turnover markers can improve quantification of bone loss in patients with myeloma (new, relapsed, smouldering) and Monoclonal Gammopathy Of Uncertain Significance (MGUS) at baseline assessment, compared to Dual-energy X-ray Absorptiometry (DXA) and established bone turnover markers alone. This particular section analysed the inter-group difference in baseline serum sclerostin bone turnover marker levels, in patients from Groups 1a (new myeloma), 1b (relapsed myeloma), 1c (smouldering myeloma) and 2 (MGUS).
Time frame: At baseline
Primary Outcome 2: Quantifying Bone Loss - Inter-Group Differences in Baseline Serum Ratio of RANKL (Receptor Activator of Nuclear Factor Kappa-Β Ligand) and OPG (Osteoprotegerin)
Primary Outcome 2: To assess whether the novel magnetic resonance (MR) protocol and exploratory bone turnover markers can improve quantification of bone loss in patients with myeloma (new, relapsed, smouldering) and Monoclonal Gammopathy Of Uncertain Significance (MGUS) at baseline assessment, compared to Dual-energy X-ray Absorptiometry (DXA) and established bone turnover markers alone. This particular section analysed the inter-group difference in baseline ratio between RANKL (Receptor Activator of Nuclear Factor Kappa-Β Ligand) and OPG (Osteoprotegerin) \[calculated as RANKL (pg/L) divided by OPG (pg/L)\] bone turnover marker levels, in patients from Groups 1a (new myeloma), 1b (relapsed myeloma), 1c (smouldering myeloma) and 2 (MGUS).
Time frame: At baseline
Primary Outcome 2: Quantifying Bone Loss (Inter-Biomarker Correlations)
Primary Outcome 2: To assess whether the novel magnetic resonance (MR) protocol and exploratory bone turnover markers can improve quantification of bone loss in patients with myeloma (new, relapsed, smouldering) and Monoclonal Gammopathy Of Uncertain Significance (MGUS) at baseline assessment, compared to Dual-energy X-ray Absorptiometry (DXA) and established bone turnover markers alone. In this particular section, Spearman's rank correlation coefficient was performed to assess correlations between all pairs of bone turnover markers, measured at baseline in a pooled cohort of participants from Groups 1 and 2: 1. P1NP (Procollagen Type 1 N-terminal Propeptide); 2. CTX-1 (Collagen Cross-Linked C-Telopeptide Type I); 3. ALP (Alkaline Phosphatase); 4. DKK1 (Dickkopf WNT Signaling Pathway Inhibitor 1); 5. Sclerostin; 6. Ratio of RANKL (Receptor Activator of Nuclear Factor Kappa-Β Ligand) to OPG (Osteoprotegerin).
Time frame: At baseline
Primary Outcome 2: Quantifying Bone Loss [Correlations Between Bone Turnover Markers, DXA (Dual-energy X-ray Absorptiometry) and ADC (Apparent Diffusion Coefficient)]
Primary Outcome 2: To assess whether the novel magnetic resonance (MR) protocol and exploratory bone turnover markers can improve quantification of bone loss in patients with myeloma (new, relapsed, smouldering) and Monoclonal Gammopathy Of Uncertain Significance (MGUS) at baseline assessment, compared to Dual-energy X-ray Absorptiometry (DXA) and established bone turnover markers alone. In this particular section, in a pooled cohort of participants from Groups 1 and 2, Spearman's rank correlation coefficients were calculated between all baseline bone turnover biomarkers and: 1. Baseline novel MR Apparent Diffusion Coefficient (ADC) measurements; 2. Baseline DXA (Dual-energy X-ray Absorptiometry) BMD (Bone Mineral Density) at lumbar spine (L1-4); 2\) Baseline DXA (Dual-energy X-ray Absorptiometry) BMD (Bone Mineral Density) at femoral neck.
Time frame: At baseline
Primary Outcome 1+2: Quantifying Tumour Burden (Total Spinal 'Hole' Volume)
* This was intended as a novel end-point produced by OCMR scientists, in which high-resolution 3D imaging of the spine and pelvis are analysed for lytic lesions (holes). * Unfortunately, we were unable to collect data for the total spinal hole volume and total spine collapse volume at the point of novel MR scan, due to technical challenges.
Time frame: At baseline
Primary Outcome 1+2: Quantifying Tumour Burden (Total Spinal 'Collapse' Volume)
* This was intended as a novel end-point produced by OCMR scientists, in which high-resolution 3D imaging of the spine and pelvis are analysed for the extent of vertebral collapse. * Unfortunately, we were unable to collect data for the total spinal hole volume and total spine collapse volume at the point of novel magnetic resonance (MR) scan, due to technical challenges.
Time frame: At baseline
Primary Outcome 1+2: Quantifying Tumour Burden [Osteotronix Fine Structural Analysis (FSA), Trabecular Wall Thickness]
* Osteotronix' fineSA® (Fine Structural Analysis, FSA) technology extracts microstructural information from Magnetic Resonance Imaging (MRI) data sets, as a correlate of trabecular wall thickness, to indicate bone remodelling. The FSA metric has been shown to correlate tightly with gold standard bone density measurements in rats \[Evans et al, 2014\] and human cadaveric spine specimens \[Rafferty et al, 2016\]. * In this study, we had collected data during the novel MR protocol at both baseline and follow-up time points. However, we were unable to complete analysis of the FSA metrics, because of disruptions due to COVID-19, therefore the results have not been possible to report.
Time frame: At baseline
Secondary Outcome 1: Detect Longitudinal Changes in Tumour Load With Therapy [MY-RADS RAC (Myeloma Response Assessment and Diagnosis System Response Assessment Classification) vs IMWG (International Myeloma Working Group) Response Group Classification]
Secondary Objective 1: To assess whether the novel Magnetic Resonance (MR) protocol can improve detection of longitudinal changes in tumour burden in patients with new or relapsed myeloma during therapy, compared to the International Myeloma Working Group (IMWG) Response Group classification alone. This section compared two indicators of therapy response: 1. IMWG Response Group classification \[1\], based on % change in serum paraprotein 2. MY-RADS RAC (Myeloma Response Assessment and Diagnosis System Response Assessment Classification) based on expert radiologist interpretation of paired novel MR imaging, guided by Messiou et. al. criteria \[2\]. Ref: 1. https://www.myeloma.org/resource-library/international-myeloma-working-group-imwg-uniform-response-criteria-multiple 2. Messiou, Christina, et al. "Guidelines for acquisition, interpretation, and reporting of whole-body MRI in myeloma: myeloma response assessment and diagnosis system (MY-RADS)." Radiology 291.1 (2019): 5-13.
Time frame: Comparison between baseline and follow-up at 6 months.
Secondary Outcome 1: Detect Longitudinal Changes in Tumour Load With Therapy [MY-RADS RAC (Myeloma Response Assessment and Diagnosis System Response Assessment Classification) vs % Change in ADC (Apparent Diffusion Coefficient)]
Secondary Objective 1: To assess whether the novel Magnetic Resonance (MR) protocol can improve detection of longitudinal changes in tumour burden in patients with new or relapsed myeloma during therapy, compared to the International Myeloma Working Group (IMWG) Response Group classification alone. This section compared two indicators of therapy response: 1. % change in Apparent Diffusion Coefficient (ADC) measurements in participants where there was a lytic bone lesion identified on both baseline and follow-up novel MR scan amenable to ADC measurement \[1\]. 2. MY-RADS RAC (Myeloma Response Assessment and Diagnosis System Response Assessment Classification) based on expert radiologist interpretation of paired novel MR imaging, guided by Messiou et. al. criteria \[1\]. Ref: \[1\] Messiou, Christina, et al. "Guidelines for acquisition, interpretation, and reporting of whole-body MRI in myeloma: myeloma response assessment and diagnosis system (MY-RADS)." Radiology 291.1 (2019): 5-13
Time frame: Comparison between baseline and follow-up at 6 month
Secondary Outcome 1: Detect Longitudinal Changes in Tumour Load With Therapy [% Change in ADC (Apparent Diffusion Coefficient) vs IMWG (International Myeloma Working Group) Response Group Classification]
Secondary Objective 1: To assess whether the novel Magnetic Resonance (MR) protocol can improve detection of longitudinal changes in tumour burden in patients with new or relapsed myeloma during therapy, compared to the International Myeloma Working Group (IMWG) Response Group classification alone. This section compared two indicators of therapy response: 1. IMWG Response Group classification \[1\], based on % change in serum paraprotein 2. % change in Apparent Diffusion Coefficient (ADC) measurements in participants where there was a lytic bone lesion identified on both baseline and follow-up novel MR scan amenable to ADC measurement \[2\]. Ref: 1. https://www.myeloma.org/resource-library/international-myeloma-working-group-imwg-uniform-response-criteria-multiple 2. Messiou, Christina, et al. "Guidelines for acquisition, interpretation, and reporting of whole-body MRI in myeloma: myeloma response assessment and diagnosis system (MY-RADS)." Radiology 291.1 (2019): 5-13
Time frame: Comparison between baseline and follow-up at 6month
Secondary Outcome 2: Detect Longitudinal Changes in Bone Microarchitecture With Therapy (% Change in Bone Turnover Markers)
Secondary Objective 2: To assess whether the novel Magnetic Resonance (MR) protocol and exploratory bone biomarkers can improve detection of longitudinal changes in bone loss in patients with myeloma (new, relapsed, smouldering) and Monoclonal Gammopathy of Undetermined Significance (MGUS) during therapy, compared to Dual-energy X-ray Absorptiometry (DXA) and established bone biomarkers alone. This section examined whether longitudinal change in bone turnover markers differed by chemotherapy responders vs non-responders. * The % change in bone biomarker measurements was expressed as a ratio of follow-up / baseline of paired measurements * Participants were classified by International Myeloma Working Group (IMWG) Response Group classification, as responder (partial response, very good partial response or complete response) or non-responder (stable, progressive or relapse).
Time frame: Comparison between baseline and follow-up at 6month
Secondary Outcome 2: Detect Longitudinal Changes in Bone Microarchitecture With Therapy (Correlations Between % Change in Bone Turnover Markers)
Secondary Objective 2: To assess whether the novel Magnetic Resonance (MR) protocol and exploratory bone biomarkers can improve detection of longitudinal changes in bone loss in patients with myeloma (new, relapsed, smouldering) and Monoclonal Gammopathy of Undetermined Significance (MGUS) during therapy, compared to Dual-energy X-ray Absorptiometry (DXA) and established bone biomarkers alone. This particular section examined the correlation between longitudinal changes in bone turnover markers between one another (calculated as a ratio of follow-up measurement divided by baseline measurement). Spearman's rank correlation was performed for the longitudinal % change between different biomarkers, to assess the relationship between longitudinal changes in these measures.
Time frame: Comparison between baseline and follow-up at 6month
Secondary Outcome 2: Detect Longitudinal Changes in Bone Microarchitecture With Therapy [Correlations Between % Change in Bone Turnover Markers With % Change in Bone Mineral Density (BMD) or Apparent Diffusion Coefficient (ADC)]
Secondary Objective 2: To assess whether the novel Magnetic Resonance (MR) protocol and exploratory bone biomarkers can improve detection of longitudinal changes in bone loss in patients with myeloma (new, relapsed, smouldering) and Monoclonal Gammopathy of Undetermined Significance (MGUS) during therapy, compared to Dual-energy X-ray Absorptiometry (DXA) and established bone biomarkers alone. This section examined the correlation (using Spearman's Rank Correlation Coefficient) between longitudinal changes (expressed as a ratio of follow-up / baseline of paired measurements) in bone turnover markers and: 1. Longitudinal changes in DXA Bone Mineral Density (BMD) at lumbar spine (L1-4) and femoral neck; 2. Longitudinal changes in novel MR Apparent Diffusion Coefficient (ADC) measurements.
Time frame: Comparison between baseline and follow-up at 6month
Secondary Objective 3: Assess Participants' Quality of Life Throughout the Study
Secondary Objective 3: To assess how quality of life compares between groups and longitudinally in patients with myeloma, Monoclonal Gammopathy of Undetermined Significance (MGUS), and healthy volunteers. The EuroQol 5-Dimension (EQ-5D) assess the mobility, self-care, usual activities, pain/discomfort, anxiety and depression on a 5-point scale, in which a lower score represents better quality of life (1 = 'no problems', 5 = maximum problems, for each domain). The second part of the EQ-5D assess health on a scale where 100 is the best health and 0 is the worst health.
Time frame: At baseline and six months
Secondary Outcome 4: Assess Participants' Experience of Novel Magnetic Resonance (MR) and Dual-energy X-ray Absorptiometry (DXA) Scans
This questionnaire assesses the experience of the Novel Magnetic Resonance (MR) and Dual-energy X-ray Absorptiometry (DXA) scans. Answers were recorded on a 5 point Likert scale where the lower number represents a better outcome. Scale descriptors: Q1 (Overall Experience): 1 (Very comfortable)/ 2 (Comfortable)/ 3 (Neither comfortable or uncomfortable)/ 4 (Uncomfortable)/ 5 (Very uncomfortable) Q2 (Adverse Effects): 1 (YES) / 0 (NO) Q3 (Length of Time): 0 (Too short) / 1 (Just right) / 2 (Too long) Q4 (Pain/Discomfort): 1 (No Increase)/ 2 (Mild Increase)/ 3 (Moderate Increase)/ 4 (High Increase)/ 5 (Severe Increase) Q5 (Likely to Reparticipate): 0 (Extremely Unlikely) / 1 (Unlikely) / 2 (Neither Likely or Unlikely) / 3 (Likely) / 4 (Extremely Likely) Q6 (How similar to expectations): 1 (YES) / 0 (NO) Q7 (Comfort with Staff): 1 (YES) / 0 (NO)
Time frame: At baseline and six months
Participants from Groups 1 and 2 were identified and approached by a healthcare professional in the oncology clinic at the Churchill Hospital, Oxford. Group 3 participants were typically partners of the participants from Groups 1 and 2 and were recruited at the same time.
| Milestone | Group 1- Myeloma | Group 2- MGUS | Group 3- Healthy Volunteers |
|---|---|---|---|
| Started | 41 | 14 | 12 |
| Baseline assessment | 41 | 14 | 12 |
| Follow-up assessment | 32 | 12 | 0 |
| Completed | 32 | 12 | 12 |
| Not completed | 9 | 2 | 0 |
| Withdrew: Withdrawal by subject | 9 | 2 | 0 |
Primary Objective 1: To assess whether the novel magnetic resonance (MR) protocol and exploratory bone biomarkers can improve quantification of tumour burden in patients with new or relapsed myeloma at baseline assessment, compared to paraprotein levels alone. This particular section analysed the correlation between the Apparent Diffusion Coefficient (ADC) measurements (from the Diffusion Weighted Magnetic Resonance Imaging (DW-MRI) component of the sequences) of lytic bone lesions, with standard clinical correlates of tumour burden (serum paraprotein, and serum paraprotein-associated immunoglobulin level). The measurement of ADC from DW-MRI is further described by Messiou et. al. \[1\] \[1\] Messiou, Christina, et al. "Guidelines for acquisition, interpretation, and reporting of whole-body MRI in myeloma: myeloma response assessment and diagnosis system (MY-RADS)." Radiology 291.1 (2019): 5-13.
| Pearson's correlation coefficient | Group 1a: New Myeloma | Group 1b: Relapsed Myeloma |
|---|---|---|
| ADC vs serum paraprotein | -0.66 (-0.99 to 0.82) | NA (NA to NA) |
| ADC vs serum paraprotein-associated immunoglobulin level | -0.28 (-0.79 to 0.48) | 0.48 (NA to NA) |
Primary Objective 1: To assess whether the novel MR protocol and exploratory bone biomarkers can improve quantification of tumour burden in patients with new or relapsed myeloma at baseline assessment, compared to paraprotein levels alone. Participants' baseline novel MR scan was analysed by an expert radiologist, and pattern of disease was qualitatively classified using the MY-RADS (Myeloma Response Assessment and Diagnosis System) imaging recommendations, described in Figure 2 by Messiou et. al. \[1\]. This particular section analysed whether standard clinical correlate of tumour burden (serum paraprotein) differed by radiological pattern of disease (e.g., normal, focal, diffuse). \[1\] Messiou, Christina, et al. "Guidelines for acquisition, interpretation, and reporting of whole-body MRI in myeloma: myeloma response assessment and diagnosis system (MY-RADS)." Radiology 291.1 (2019): 5-13.
| grams per liter (g/L) | MY-RADS: Normal | MY-RADS: Focal | MY-RADS: Micronodular | MY-RADS: Not Determined |
|---|---|---|---|---|
| Primary Outcome 1: Quantifying Tumour Burden [Correlations With Myeloma Response Assessment and Diagnosis System (MY-RADS) Pattern of Disease] | 13.1 ± 9.4 | 11.7 ± 7.8 | 5.4 ± NA | 17.2 ± NA |
Primary Objective 1: To assess whether the novel Magnetic Resonance (MR) protocol and exploratory bone biomarkers can improve quantification of tumour burden in patients with new or relapsed myeloma at baseline assessment, compared to paraprotein levels alone. This section examined correlation between baseline bone biomarkers and baseline serum paraprotein in a pooled cohort of patients from Groups 1 and 2, using Spearman's Rank Correlation Coefficients.
| Spearman's rank correlation coefficient | Baseline P1NP | Baseline CTX-1 | Baseline ALP | Baseline DKK1 | Baseline Sclerostin | Baseline RANKL:OPG |
|---|---|---|---|---|---|---|
| Primary Outcome 1: Quantifying Tumour Burden (Correlations With Bone Turnover Markers) | 0.31 (-0.10 to 0.64) | 0.01 (-0.41 to 0.42) | -0.18 (-0.54 to 0.24) | 0.39 (0.00 to 0.68) | 0.23 (-0.17 to 0.57) | -0.02 (-0.42 to 0.38) |
Primary Outcome 2: To assess whether the novel magnetic resonance (MR) protocol and exploratory bone turnover markers can improve quantification of bone loss in patients with myeloma (new, relapsed, smouldering) and Monoclonal Gammopathy Of Uncertain Significance (MGUS) at baseline assessment, compared to Dual-energy X-ray Absorptiometry (DXA) and established bone turnover markers alone. This particular section analysed the inter-group difference in baseline serum P1NP (Procollagen Type 1 N-terminal Propeptide) bone turnover marker levels, in patients from Groups 1a (new myeloma), 1b (relapsed myeloma), 1c (smouldering myeloma) and 2 (MGUS).
| microgram per litre | Group 1a: New Myeloma | Group 1b: Relapsed Myeloma | Group 1c: Smouldering Myeloma | Group 2: MGUS |
|---|---|---|---|---|
| Primary Outcome 2: Quantifying Bone Loss - Inter-Group Differences in Baseline Serum P1NP (Procollagen Type 1 N-terminal Propeptide) | 38.6 ± 23.1 | 39.5 ± 24.0 | 39.6 ± 23.1 | 39.3 ± 23.3 |
Primary Outcome 2: To assess whether the novel magnetic resonance (MR) protocol and exploratory bone turnover markers can improve quantification of bone loss in patients with myeloma (new, relapsed, smouldering) and Monoclonal Gammopathy Of Uncertain Significance (MGUS) at baseline assessment, compared to Dual-energy X-ray Absorptiometry (DXA) and established bone turnover markers alone. This particular section analysed the inter-group difference in baseline serum CTX-1 (Collagen Cross-Linked C-Telopeptide Type I) bone turnover marker levels, in patients from Groups 1a (new myeloma), 1b (relapsed myeloma), 1c (smouldering myeloma) and 2 (MGUS).
| microgram per litre | Group 1a: New Myeloma | Group 1b: Relapsed Myeloma | Group 1c: Smouldering Myeloma | Group 2: MGUS |
|---|---|---|---|---|
| Primary Outcome 2: Quantifying Bone Loss - Inter-Group Differences in Baseline Serum CTX-1 (Collagen Cross-Linked C-Telopeptide Type I) | 0.38 ± 0.33 | 0.40 ± 0.35 | 0.39 ± 0.32 | 0.39 ± 0.32 |
Primary Outcome 2: To assess whether the novel magnetic resonance (MR) protocol and exploratory bone turnover markers can improve quantification of bone loss in patients with myeloma (new, relapsed, smouldering) and Monoclonal Gammopathy Of Uncertain Significance (MGUS) at baseline assessment, compared to Dual-energy X-ray Absorptiometry (DXA) and established bone turnover markers alone. This particular section analysed the inter-group difference in baseline serum ALP (Alkaline Phosphatase) bone turnover marker levels, in patients from Groups 1a (new myeloma), 1b (relapsed myeloma), 1c (smouldering myeloma) and 2 (MGUS).
| international units per litre | Group 1a: New Myeloma | Group 1b: Relapsed Myeloma | Group 1c: Smouldering Myeloma | Group 2: MGUS |
|---|---|---|---|---|
| Primary Outcome 2: Quantifying Bone Loss - Inter-Group Differences in Baseline Serum ALP (Alkaline Phosphatase) | 73.8 ± 34.2 | 73.3 ± 34.9 | 72.2 ± 32.0 | 74.0 ± 33.6 |
Primary Outcome 2: To assess whether the novel magnetic resonance (MR) protocol and exploratory bone turnover markers can improve quantification of bone loss in patients with myeloma (new, relapsed, smouldering) and Monoclonal Gammopathy Of Uncertain Significance (MGUS) at baseline assessment, compared to Dual-energy X-ray Absorptiometry (DXA) and established bone turnover markers alone. This particular section analysed the inter-group difference in baseline serum DKK1 (Dickkopf WNT Signaling Pathway Inhibitor 1) bone turnover marker levels, in patients from Groups 1a (new myeloma), 1b (relapsed myeloma), 1c (smouldering myeloma) and 2 (MGUS).
| picogram per litre | Group 1a: New Myeloma | Group 1b: Relapsed Myeloma | Group 1c: Smouldering Myeloma | Group 2: MGUS |
|---|---|---|---|---|
| Primary Outcome 2: Quantifying Bone Loss - Inter-Group Differences in Baseline Serum DKK1 (Dickkopf WNT Signaling Pathway Inhibitor 1) | 3963.6 ± 3666.8 | 4018.9 ± 3506.5 | 3759.2 ± 3175.6 | 3924.5 ± 3568.6 |
Primary Outcome 2: To assess whether the novel magnetic resonance (MR) protocol and exploratory bone turnover markers can improve quantification of bone loss in patients with myeloma (new, relapsed, smouldering) and Monoclonal Gammopathy Of Uncertain Significance (MGUS) at baseline assessment, compared to Dual-energy X-ray Absorptiometry (DXA) and established bone turnover markers alone. This particular section analysed the inter-group difference in baseline serum sclerostin bone turnover marker levels, in patients from Groups 1a (new myeloma), 1b (relapsed myeloma), 1c (smouldering myeloma) and 2 (MGUS).
| picogram per litre | Group 1a: New Myeloma | Group 1b: Relapsed Myeloma | Group 1c: Smouldering Myeloma | Group 2: MGUS |
|---|---|---|---|---|
| Primary Outcome 2: Quantifying Bone Loss - Inter-Group Differences in Baseline Serum Sclerostin | 168.5 ± 84.1 | 165.5 ± 85.1 | 166.9 ± 86.9 | 164.9 ± 83.6 |
Primary Outcome 2: To assess whether the novel magnetic resonance (MR) protocol and exploratory bone turnover markers can improve quantification of bone loss in patients with myeloma (new, relapsed, smouldering) and Monoclonal Gammopathy Of Uncertain Significance (MGUS) at baseline assessment, compared to Dual-energy X-ray Absorptiometry (DXA) and established bone turnover markers alone. This particular section analysed the inter-group difference in baseline ratio between RANKL (Receptor Activator of Nuclear Factor Kappa-Β Ligand) and OPG (Osteoprotegerin) \[calculated as RANKL (pg/L) divided by OPG (pg/L)\] bone turnover marker levels, in patients from Groups 1a (new myeloma), 1b (relapsed myeloma), 1c (smouldering myeloma) and 2 (MGUS).
| RANKL (pg/L) to OPG (pg/L) ratio | Group 1a: New Myeloma | Group 1b: Relapsed Myeloma | Group 1c: Smouldering Myeloma | Group 2: MGUS |
|---|---|---|---|---|
| Primary Outcome 2: Quantifying Bone Loss - Inter-Group Differences in Baseline Serum Ratio of RANKL (Receptor Activator of Nuclear Factor Kappa-Β Ligand) and OPG (Osteoprotegerin) | 0.0170 ± 0.0205 | 0.0176 ± 0.0221 | 0.0397 ± 0.1524 | 0.0386 ± 0.1494 |
Primary Outcome 2: To assess whether the novel magnetic resonance (MR) protocol and exploratory bone turnover markers can improve quantification of bone loss in patients with myeloma (new, relapsed, smouldering) and Monoclonal Gammopathy Of Uncertain Significance (MGUS) at baseline assessment, compared to Dual-energy X-ray Absorptiometry (DXA) and established bone turnover markers alone. In this particular section, Spearman's rank correlation coefficient was performed to assess correlations between all pairs of bone turnover markers, measured at baseline in a pooled cohort of participants from Groups 1 and 2: 1. P1NP (Procollagen Type 1 N-terminal Propeptide); 2. CTX-1 (Collagen Cross-Linked C-Telopeptide Type I); 3. ALP (Alkaline Phosphatase); 4. DKK1 (Dickkopf WNT Signaling Pathway Inhibitor 1); 5. Sclerostin; 6. Ratio of RANKL (Receptor Activator of Nuclear Factor Kappa-Β Ligand) to OPG (Osteoprotegerin).
| Spearman's rank correlation coefficient | Baseline CTX-1 | Baseline ALP | Baseline DKK1 | Baseline Sclerostin | Baseline RANKL:OPG |
|---|---|---|---|---|---|
| Baseline P1NP (Spearman's Rank Correlation Coefficient) | 0.70 (0.51 to 0.82) | 0.37 (0.10 to 0.58) | 0.12 (-0.16 to 0.39) | 0.22 (-0.07 to 0.47) | -0.10 (-0.37 to 0.19) |
| Baseline CTX-1 (Spearman's Rank Correlation Coefficient) | — | 0.25 (-0.04 to 0.50) | 0.00 (-0.28 to 0.29) | 0.32 (0.03 to 0.55) | -0.21 (-0.47 to 0.09) |
| Baseline ALP (Spearman's Rank Correlation Coefficient) | — | — | 0.09 (-0.19 to 0.36) | -0.04 (-0.31 to 0.24) | -0.23 (-0.48 to 0.06) |
| Baseline DKK1 (Spearman's Rank Correlation Coefficient) | — | — | — | 0.11 (-0.16 to 0.37) | 0.13 (-0.15 to 0.39) |
| Baseline Sclerostin (Spearman's Rank Correlation Coefficient) | — | — | — | — | -0.29 (-0.53 to -0.01) |
Primary Outcome 2: To assess whether the novel magnetic resonance (MR) protocol and exploratory bone turnover markers can improve quantification of bone loss in patients with myeloma (new, relapsed, smouldering) and Monoclonal Gammopathy Of Uncertain Significance (MGUS) at baseline assessment, compared to Dual-energy X-ray Absorptiometry (DXA) and established bone turnover markers alone. In this particular section, in a pooled cohort of participants from Groups 1 and 2, Spearman's rank correlation coefficients were calculated between all baseline bone turnover biomarkers and: 1. Baseline novel MR Apparent Diffusion Coefficient (ADC) measurements; 2. Baseline DXA (Dual-energy X-ray Absorptiometry) BMD (Bone Mineral Density) at lumbar spine (L1-4); 2\) Baseline DXA (Dual-energy X-ray Absorptiometry) BMD (Bone Mineral Density) at femoral neck.
| Spearman's rank correlation coefficient | Baseline P1NP | Baseline CTX-1 | Baseline ALP | Baseline DKK1 | Baseline Sclerostin | Baseline RANKL:OPG |
|---|---|---|---|---|---|---|
| DXA BMD for L1-4 (Spearman's Rank Correlation Coefficient) | 0.02 (-0.26 to 0.29) | 0.00 (-0.29 to 0.29) | 0.16 (-0.12 to 0.41) | 0.25 (-0.03 to 0.49) | 0.54 (0.31 to 0.71) | -0.02 (-0.30 to 0.26) |
| DXA BMD for Femoral Neck (Spearman's Rank Correlation Coefficient) | 0.09 (-0.20 to 0.37) | 0.14 (-0.16 to 0.41) | 0.11 (-0.17 to 0.38) | 0.19 (-0.10 to 0.44) | 0.40 (0.13 to 0.61) | 0.10 (-0.19 to 0.37) |
| Novel MR ADC Measurement (Spearman's Rank Correlation Coefficient) | 0.09 (-0.52 to 0.64) | -0.06 (NA to NA) | -0.27 (-0.74 to 0.37) | -0.01 (-0.59 to 0.58) | -0.42 (-0.81 to 0.21) | 0.09 (-0.30 to 0.26) |
* This was intended as a novel end-point produced by OCMR scientists, in which high-resolution 3D imaging of the spine and pelvis are analysed for lytic lesions (holes). * Unfortunately, we were unable to collect data for the total spinal hole volume and total spine collapse volume at the point of novel MR scan, due to technical challenges.
No measurements were reported for this outcome.
* This was intended as a novel end-point produced by OCMR scientists, in which high-resolution 3D imaging of the spine and pelvis are analysed for the extent of vertebral collapse. * Unfortunately, we were unable to collect data for the total spinal hole volume and total spine collapse volume at the point of novel magnetic resonance (MR) scan, due to technical challenges.
No measurements were reported for this outcome.
* Osteotronix' fineSA® (Fine Structural Analysis, FSA) technology extracts microstructural information from Magnetic Resonance Imaging (MRI) data sets, as a correlate of trabecular wall thickness, to indicate bone remodelling. The FSA metric has been shown to correlate tightly with gold standard bone density measurements in rats \[Evans et al, 2014\] and human cadaveric spine specimens \[Rafferty et al, 2016\]. * In this study, we had collected data during the novel MR protocol at both baseline and follow-up time points. However, we were unable to complete analysis of the FSA metrics, because of disruptions due to COVID-19, therefore the results have not been possible to report.
No measurements were reported for this outcome.
Secondary Objective 1: To assess whether the novel Magnetic Resonance (MR) protocol can improve detection of longitudinal changes in tumour burden in patients with new or relapsed myeloma during therapy, compared to the International Myeloma Working Group (IMWG) Response Group classification alone. This section compared two indicators of therapy response: 1. IMWG Response Group classification \[1\], based on % change in serum paraprotein 2. MY-RADS RAC (Myeloma Response Assessment and Diagnosis System Response Assessment Classification) based on expert radiologist interpretation of paired novel MR imaging, guided by Messiou et. al. criteria \[2\]. Ref: 1. https://www.myeloma.org/resource-library/international-myeloma-working-group-imwg-uniform-response-criteria-multiple 2. Messiou, Christina, et al. "Guidelines for acquisition, interpretation, and reporting of whole-body MRI in myeloma: myeloma response assessment and diagnosis system (MY-RADS)." Radiology 291.1 (2019): 5-13.
| Participants | IMWG: Relapse | IMWG: Progressive | IMWG: Stable | IMWG: Partial Response | IMWG: Very Good Partial Response | IMWG: Complete Response |
|---|---|---|---|---|---|---|
| MY-RADS RAC 1: Highly likely to be responding | 0 | 0 | 0 | 2 | 3 | 0 |
| MY-RADS RAC 2: Likely to be responding | 0 | 1 | 0 | 4 | 0 | 0 |
| MY-RADS RAC 3: Stable | 1 | 3 | 8 | 3 | 1 | 1 |
Secondary Objective 1: To assess whether the novel Magnetic Resonance (MR) protocol can improve detection of longitudinal changes in tumour burden in patients with new or relapsed myeloma during therapy, compared to the International Myeloma Working Group (IMWG) Response Group classification alone. This section compared two indicators of therapy response: 1. % change in Apparent Diffusion Coefficient (ADC) measurements in participants where there was a lytic bone lesion identified on both baseline and follow-up novel MR scan amenable to ADC measurement \[1\]. 2. MY-RADS RAC (Myeloma Response Assessment and Diagnosis System Response Assessment Classification) based on expert radiologist interpretation of paired novel MR imaging, guided by Messiou et. al. criteria \[1\]. Ref: \[1\] Messiou, Christina, et al. "Guidelines for acquisition, interpretation, and reporting of whole-body MRI in myeloma: myeloma response assessment and diagnosis system (MY-RADS)." Radiology 291.1 (2019): 5-13
| ADC Ratio (follow-up / baseline) | Group 1a: New Myeloma | Group 1b: Relapsed Myeloma |
|---|---|---|
| MY-RADS RAC 1: Highly likely to be responding | 0.45 ± NA | 1.40 ± NA |
| MY-RADS RAC 2: Likely to be responding | 1.29 ± 0.45 | 0.57 ± NA |
| MY-RADS RAC 3: Stable | 1.61 ± 0.45 | — |
Secondary Objective 1: To assess whether the novel Magnetic Resonance (MR) protocol can improve detection of longitudinal changes in tumour burden in patients with new or relapsed myeloma during therapy, compared to the International Myeloma Working Group (IMWG) Response Group classification alone. This section compared two indicators of therapy response: 1. IMWG Response Group classification \[1\], based on % change in serum paraprotein 2. % change in Apparent Diffusion Coefficient (ADC) measurements in participants where there was a lytic bone lesion identified on both baseline and follow-up novel MR scan amenable to ADC measurement \[2\]. Ref: 1. https://www.myeloma.org/resource-library/international-myeloma-working-group-imwg-uniform-response-criteria-multiple 2. Messiou, Christina, et al. "Guidelines for acquisition, interpretation, and reporting of whole-body MRI in myeloma: myeloma response assessment and diagnosis system (MY-RADS)." Radiology 291.1 (2019): 5-13
| ADC Ratio (follow-up / baseline) | Group 1a: New Myeloma | Group 1b: Relapsed Myeloma |
|---|---|---|
| IMWG: Progressive | 1.6 ± NA | — |
| IMWG: Partial Response | 0.90 ± 0.42 | 0.99 ± 0.59 |
| IMWG: Very Good Partial Response | 1.9 ± NA | — |
Secondary Objective 2: To assess whether the novel Magnetic Resonance (MR) protocol and exploratory bone biomarkers can improve detection of longitudinal changes in bone loss in patients with myeloma (new, relapsed, smouldering) and Monoclonal Gammopathy of Undetermined Significance (MGUS) during therapy, compared to Dual-energy X-ray Absorptiometry (DXA) and established bone biomarkers alone. This section examined whether longitudinal change in bone turnover markers differed by chemotherapy responders vs non-responders. * The % change in bone biomarker measurements was expressed as a ratio of follow-up / baseline of paired measurements * Participants were classified by International Myeloma Working Group (IMWG) Response Group classification, as responder (partial response, very good partial response or complete response) or non-responder (stable, progressive or relapse).
| Ratio (follow-up divided by baseline) | % Change in P1NP | % Change in CTX-1 | % Change in ALP | % Change in DKK1 | % Change in Sclerostin | % Change in RANKL:OPG |
|---|---|---|---|---|---|---|
| IMWG Responder | 0.94 ± 0.75 | 0.89 ± 0.73 | 0.85 ± 0.22 | 0.63 ± 0.40 | 1.22 ± 0.64 | 1.09 ± 0.81 |
| IMWG Non-Responder | 0.95 ± 0.21 | 1.18 ± 0.51 | 0.98 ± 0.23 | 1.15 ± 0.59 | 1.18 ± 0.41 | 1.51 ± 1.04 |
Secondary Objective 2: To assess whether the novel Magnetic Resonance (MR) protocol and exploratory bone biomarkers can improve detection of longitudinal changes in bone loss in patients with myeloma (new, relapsed, smouldering) and Monoclonal Gammopathy of Undetermined Significance (MGUS) during therapy, compared to Dual-energy X-ray Absorptiometry (DXA) and established bone biomarkers alone. This particular section examined the correlation between longitudinal changes in bone turnover markers between one another (calculated as a ratio of follow-up measurement divided by baseline measurement). Spearman's rank correlation was performed for the longitudinal % change between different biomarkers, to assess the relationship between longitudinal changes in these measures.
| Spearman's rank correlation coefficient | % Change in CTX-1 | % Change in ALP | % Change in DKK1 | % Change in Sclerostin | % Change in RANKL:OPG |
|---|---|---|---|---|---|
| % Change in P1NP | 0.41 (0.10 to 0.64) | 0.36 (0.05 to 0.61) | 0.12 (-0.20 to 0.41) | 0.32 (0.00 to 0.58) | 0.41 (0.09 to 0.65) |
| % Change in CTX-1 | — | 0.08 (-0.24 to 0.39) | 0.11 (-0.22 to 0.42) | 0.26 (-0.08 to 0.54) | -0.03 (-0.37 to 0.32) |
| % Change in ALP | — | — | 0.23 (-0.08 to 0.51) | -0.01 (-0.32 to 0.31) | -0.13 (-0.44 to 0.21) |
| % Change in DKK1 | — | — | — | 0.13 (-0.18 to 0.43) | 0.14 (-0.20 to 0.44) |
| % Change in Sclerostin | — | — | — | — | 0.37 (0.06 to 0.62) |
Secondary Objective 2: To assess whether the novel Magnetic Resonance (MR) protocol and exploratory bone biomarkers can improve detection of longitudinal changes in bone loss in patients with myeloma (new, relapsed, smouldering) and Monoclonal Gammopathy of Undetermined Significance (MGUS) during therapy, compared to Dual-energy X-ray Absorptiometry (DXA) and established bone biomarkers alone. This section examined the correlation (using Spearman's Rank Correlation Coefficient) between longitudinal changes (expressed as a ratio of follow-up / baseline of paired measurements) in bone turnover markers and: 1. Longitudinal changes in DXA Bone Mineral Density (BMD) at lumbar spine (L1-4) and femoral neck; 2. Longitudinal changes in novel MR Apparent Diffusion Coefficient (ADC) measurements.
| Spearman's rank correlation coefficient | % Change in P1NP | % Change in CTX-1 | % Change in ALP | % Change in DKK1 | % Change in Sclerostin | % Change in RANKL:OPG |
|---|---|---|---|---|---|---|
| % Change in Novel MR ADC | -0.39 (NA to NA) | 0.31 (NA to NA) | -0.50 (NA to NA) | -0.32 (NA to NA) | -0.32 (NA to NA) | -0.14 (NA to NA) |
| % Change in DXA BMD (L1-4) | -0.12 (-0.42 to 0.21) | -0.10 (-0.41 to 0.23) | 0.02 (-0.29 to 0.33) | 0.02 (-0.29 to 0.33) | 0.24 (-0.08 to 0.51) | -0.17 (-0.48 to 0.16) |
| % Change in DXA BMD (Femoral Neck) | -0.20 (-0.50 to 0.13) | -0.10 (-0.41 to 0.24) | -0.17 (-0.47 to 0.16) | -0.09 (-0.39 to 0.24) | 0.00 (-0.32 to 0.32) | -0.45 (-0.68 to -0.13) |
Secondary Objective 3: To assess how quality of life compares between groups and longitudinally in patients with myeloma, Monoclonal Gammopathy of Undetermined Significance (MGUS), and healthy volunteers. The EuroQol 5-Dimension (EQ-5D) assess the mobility, self-care, usual activities, pain/discomfort, anxiety and depression on a 5-point scale, in which a lower score represents better quality of life (1 = 'no problems', 5 = maximum problems, for each domain). The second part of the EQ-5D assess health on a scale where 100 is the best health and 0 is the worst health.
| Scores on a scale | Group 1- Myeloma | Group 2- MGUS | Group 3- Healthy Volunteers |
|---|---|---|---|
| Baseline: Mobility | 1.29 ± 0.46 | 1.23 ± 0.44 | 1.00 ± 0.00 |
| Baseline: Self-Care | 1.11 ± 0.31 | 1.08 ± 0.28 | 1.00 ± 0.00 |
| Baseline: Usual Activities | 1.45 ± 0.65 | 1.15 ± 0.38 | 1.00 ± 0.00 |
| Baseline: Pain/Discomfort | 1.63 ± 0.63 | 1.54 ± 0.52 | 1.08 ± 0.29 |
| Baseline: Anxiety/Depression | 1.11 ± 0.31 | 1.08 ± 0.28 | 1.00 ± 0.00 |
| Baseline: Health Score | 72.8 ± 22.6 | 83.9 ± 7.7 | 87.9 ± 5.9 |
| Follow-Up: Mobility | 1.34 ± 0.48 | 1.33 ± 0.49 | — |
| Follow-Up: Self-Care | 1.07 ± 0.26 | 1.17 ± 0.39 | — |
| Follow-Up: Usual Activities | 1.38 ± 0.49 | 1.25 ± 0.45 | — |
| Follow-Up: Pain/Discomfort | 1.59 ± 0.63 | 1.42 ± 0.51 | — |
| Follow-Up: Anxiety/Depression | 1.21 ± 0.41 | 1.08 ± 0.29 | — |
| Follow-Up: Health Score | 75.1 ± 20.5 | 79.0 ± 15.6 | — |
This questionnaire assesses the experience of the Novel Magnetic Resonance (MR) and Dual-energy X-ray Absorptiometry (DXA) scans. Answers were recorded on a 5 point Likert scale where the lower number represents a better outcome. Scale descriptors: Q1 (Overall Experience): 1 (Very comfortable)/ 2 (Comfortable)/ 3 (Neither comfortable or uncomfortable)/ 4 (Uncomfortable)/ 5 (Very uncomfortable) Q2 (Adverse Effects): 1 (YES) / 0 (NO) Q3 (Length of Time): 0 (Too short) / 1 (Just right) / 2 (Too long) Q4 (Pain/Discomfort): 1 (No Increase)/ 2 (Mild Increase)/ 3 (Moderate Increase)/ 4 (High Increase)/ 5 (Severe Increase) Q5 (Likely to Reparticipate): 0 (Extremely Unlikely) / 1 (Unlikely) / 2 (Neither Likely or Unlikely) / 3 (Likely) / 4 (Extremely Likely) Q6 (How similar to expectations): 1 (YES) / 0 (NO) Q7 (Comfort with Staff): 1 (YES) / 0 (NO)
| Score on a scale (see description above) | Group 1- Myeloma | Group 2- MGUS | Group 3- Healthy Volunteers |
|---|---|---|---|
| Baseline novel MR scan experience: Q1 = Overall Experience | 2.10 ± 0.91 | 2.10 ± 0.93 | 2.13 ± 0.92 |
| Baseline novel MR scan experience: Q2 = Adverse Effects | 0.30 ± 0.46 | 0.31 ± 0.47 | 0.33 ± 0.47 |
| Baseline novel MR scan experience: Q3 = Length of Time | 1.39 ± 0.49 | 1.40 ± 0.49 | 1.40 ± 0.50 |
| Baseline novel MR scan experience: Q4 = Pain/Discomfort | 1.75 ± 0.86 | 1.74 ± 0.87 | 1.73 ± 0.89 |
| Baseline novel MR scan experience: Q5 = How Likely to Re-participate | 3.34 ± 0.91 | 3.36 ± 0.92 | 3.34 ± 0.96 |
| Baseline novel MR scan experience: Q6 = How Similar to Expectations | 1.00 ± 0.00 | 1.00 ± 0.00 | 1.00 ± 0.00 |
| Baseline novel MR scan experience: Q7 = Comfort with Staff | 1.00 ± 0.00 | 1.00 ± 0.00 | 1.00 ± 0.00 |
| Follow-up novel MR scan experience: Q1 = Overall Experience | 2.17 ± 1.07 | 2.20 ± 1.11 | — |
| Follow-up novel MR scan experience: Q2 = Adverse Effects | 0.27 ± 0.45 | 0.28 ± 0.45 | — |
| Follow-up novel MR scan experience: Q3 = Length of Time | 1.30 ± 0.46 | 1.33 ± 0.48 | — |
| Follow-up novel MR scan experience: Q4 = Pain/Discomfort | 1.44 ± 0.71 | 1.48 ± 0.82 | — |
| Follow-up novel MR scan experience: Q5 = How Likely to Re-participate | 3.29 ± 1.05 | 3.33 ± 1.05 | — |
| Follow-up novel MR scan experience: Q6 = How Similar to Expectations | 1.00 ± 0.00 | 1.00 ± 0.00 | — |
| Follow-up novel MR scan experience: Q7 = Comfort with Staff | 1.00 ± 0.00 | 0.98 ± 0.16 | — |
| Baseline DXA scan experience: Q1 = Overall Experience | 1.58 ± 0.72 | 1.61 ± 0.72 | — |
| Baseline DXA scan experience: Q2 = Adverse Effects | 0.11 ± 0.32 | 0.12 ± 0.33 | — |
| Baseline DXA scan experience: Q3 = Length of Time | 1.00 ± 0.00 | 1.00 ± 0.00 | — |
| Baseline DXA scan experience: Q4 = Pain/Discomfort | 1.17 ± 0.43 | 1.16 ± 0.42 | — |
| Baseline DXA scan experience: Q5 = How Likely to Re-participate | 3.51 ± 0.85 | 3.53 ± 0.83 | — |
| Baseline DXA scan experience: Q6 = How Similar to Expectations | 0.98 ± 0.14 | 0.98 ± 0.14 | — |
| Baseline DXA scan experience: Q7 = Comfort with Staff | 1.00 ± 0.00 | 1.00 ± 0.00 | — |
| Follow-up DXA scan experience: Q1 = Overall Experience | 1.65 ± 0.75 | 1.71 ± 0.83 | — |
| Follow-up DXA scan experience: Q2 = Adverse Effects | 0.09 ± 0.29 | 0.10 ± 0.30 | — |
| Follow-up DXA scan experience: Q3 = Length of Time | 1.05 ± 0.21 | 1.07 ± 0.26 | — |
| Follow-up DXA scan experience: Q4 = Pain/Discomfort | 1.12 ± 0.32 | 1.19 ± 0.55 | — |
| Follow-up DXA scan experience: Q5 = How Likely to Re-participate | 3.63 ± 0.85 | 3.67 ± 0.85 | — |
| Follow-up DXA scan experience: Q6 = How Similar to Expectations | 1.00 ± 1.00 | 1.00 ± 0.00 | — |
| Follow-up DXA scan experience: Q7 = Comfort with Staff | 1.00 ± 1.00 | 0.98 ± 0.15 | — |
We first addressed an important practical limitation of the study design. Patients with new myeloma usually commenced chemotherapy imminently after their diagnosis, typically a few months before they were able to consent for the present study. Therefore, most patients had already started chemotherapy at the point of baseline novel Magnetic Resonance (MR) scan, and had received variable durations of chemotherapy at baseline and follow-up scans. We hypothesised that this may be a potential confounding factor, as more recent chemotherapy may reduce tumour cellularity and therefore increase diffusion \[and therefore Apparent Diffusion Coefficient (ADC) measurements\] at lytic bone lesions. In this particular section, we analysed the difference between baseline ADC measurements in patients with new and relapsed myeloma, grouped by time elapsed since chemotherapy (ongoing, recent or never chemotherapy).
| s/mm^2 (ADC measurement unit) | Group 1a: New Myeloma | Group 1b: Relapsed Myeloma |
|---|---|---|
| Baseline ADC: Ongoing Chemotherapy | 1084.5 ± 432.5 | 1215.3 ± 319.4 |
| Baseline ADC: Recent (<1yr) Chemotherapy | — | 751.7 ± 134.8 |
| Baseline ADC: Never Chemotherapy | 547.5 ± 74.2 | — |
We first addressed an important practical limitation of the study design. Patients with new myeloma usually commenced chemotherapy imminently after their diagnosis, typically a few months before they were able to consent for the present study. Therefore, most patients had already started chemotherapy at the point of baseline novel Magnetic Resonance (MR) scan, and had received variable durations of chemotherapy at baseline and follow-up scans. We hypothesised that this may be a potential confounding factor, as more recent chemotherapy may reduce tumour cellularity and therefore increase diffusion \[and therefore Apparent Diffusion Coefficient (ADC) measurements\] at lytic bone lesions. In this particular section, we analysed the difference between follow-up ADC measurements in patients with new and relapsed myeloma, grouped by time elapsed since chemotherapy (ongoing, recent or never chemotherapy).
| s/mm^2 (ADC measurement unit) | Group 1a: New Myeloma | Group 1b: Relapsed Myeloma |
|---|---|---|
| Follow-Up ADC: Ongoing Chemotherapy | 1875 ± 205 | 1415 ± 968.7 |
| Follow-Up ADC: Recent (<1yr) Chemotherapy | 1252.3 ± 634.7 | 900 |
| Follow-Up ADC: Historic Chemotherapy (>1yr) | — | 648 |
Collected over The intention of this study was to assess the value of disease assessment of candidate biomarkers (using DW-MRI and analysis of peripheral blood). Therefore, all-Cause Mortality, Serious, and Other [Not Including Serious] Adverse Events were not monitored/assessed.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Group 1- Myeloma | — | — | — |
| Group 2- MGUS | — | — | — |
| Group 3- Healthy Volunteers | — | — | — |
Total 67 participants: Group 1a (new myeloma = 14), Group 1b (relapsed myeloma = 12), Group 1c (smouldering myeloma = 15), Group 2 (MGUS = 14), Group 3 (healthy volunteer = 12)
| Age, Categorical(Participants) | Group 1- Myeloma | Group 2- MGUS | Group 3- Healthy Volunteers | Total |
|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 17 | 7 | 7 | 31 |
| >=65 years | 24 | 7 | 5 | 36 |
| Age, Continuous(years) | Group 1- Myeloma | Group 2- MGUS | Group 3- Healthy Volunteers | Total |
|---|---|---|---|---|
| Median | 67.7 (40.9 to 85.3) | 65.5 (54.3 to 82.3) | 60.5 (35.2 to 75.5) | 65.6 (35.2 to 85.3) |
| Sex: Female, Male(Participants) | Group 1- Myeloma | Group 2- MGUS | Group 3- Healthy Volunteers | Total |
|---|---|---|---|---|
| Female | 11 | 7 | 5 | 23 |
| Male | 30 | 7 | 7 | 44 |
| Race and Ethnicity Not Collected(Participants) | Group 1- Myeloma | Group 2- MGUS | Group 3- Healthy Volunteers | Total |
|---|---|---|---|---|
| Count of participants | — | — | — | 0 |
| Region of Enrollment(participants) | Group 1- Myeloma | Group 2- MGUS | Group 3- Healthy Volunteers | Total |
|---|---|---|---|---|
| United Kingdom | 41 | 14 | 12 | 67 |
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Oxford University Hospitals NHS Trust