Trial Outcomes & Findings for The Development and Pilot Testing of a New MR Imaging Protocol to Quantify Myeloma Disease Burden and Bone Loss (NCT NCT03951220)
NCT ID: NCT03951220
Last Updated: 2025-08-19
Results Overview
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.
COMPLETED
67 participants
At baseline
2025-08-19
Participant Flow
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.
Participant milestones
| Measure |
Group 1- Myeloma
Group 1a: New Myeloma; Group 1b: Relapsed Myeloma Group;1c: Smouldering Myeloma
Baseline AND Follow-Up Assessment:
Novel MR Whole body DXA scan Blood and urine samples QOL \& scan experience questionnaires
|
Group 2- MGUS
Baseline AND Follow-Up Assessment:
Novel MR Whole body DXA scan Blood and urine samples QOL \& scan experience questionnaires
|
Group 3- Healthy Volunteers
Baseline Assessment ONLY:
* Novel MR
* QOL \& scan experience questionnaires
|
|---|---|---|---|
|
Overall Study
STARTED
|
41
|
14
|
12
|
|
Overall Study
Baseline Assessment
|
41
|
14
|
12
|
|
Overall Study
Follow-Up Assessment
|
32
|
12
|
0
|
|
Overall Study
COMPLETED
|
32
|
12
|
12
|
|
Overall Study
NOT COMPLETED
|
9
|
2
|
0
|
Reasons for withdrawal
| Measure |
Group 1- Myeloma
Group 1a: New Myeloma; Group 1b: Relapsed Myeloma Group;1c: Smouldering Myeloma
Baseline AND Follow-Up Assessment:
Novel MR Whole body DXA scan Blood and urine samples QOL \& scan experience questionnaires
|
Group 2- MGUS
Baseline AND Follow-Up Assessment:
Novel MR Whole body DXA scan Blood and urine samples QOL \& scan experience questionnaires
|
Group 3- Healthy Volunteers
Baseline Assessment ONLY:
* Novel MR
* QOL \& scan experience questionnaires
|
|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
9
|
2
|
0
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Group 1- Myeloma
n=41 Participants
Group 1a: New Myeloma Group 1b: Relapsed Myeloma Group 1c: Smouldering Myeloma
Baseline AND Follow-Up Assessment:
* Novel MR
* Whole body DXA scan
* Blood and urine samples
* QOL \& scan experience questionnaires
|
Group 2- MGUS
n=14 Participants
Baseline AND Follow-Up Assessment:
* Novel MR
* Whole body DXA scan
* Blood and urine samples
* QOL \& scan experience questionnaires
|
Group 3- Healthy Volunteers
n=12 Participants
Baseline Assessment ONLY:
* Novel MR
* QOL \& scan experience questionnaires
|
Total
n=67 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=41 Participants
|
0 Participants
n=14 Participants
|
0 Participants
n=12 Participants
|
0 Participants
n=67 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
17 Participants
n=41 Participants
|
7 Participants
n=14 Participants
|
7 Participants
n=12 Participants
|
31 Participants
n=67 Participants
|
|
Age, Categorical
>=65 years
|
24 Participants
n=41 Participants
|
7 Participants
n=14 Participants
|
5 Participants
n=12 Participants
|
36 Participants
n=67 Participants
|
|
Age, Continuous
|
67.7 years
n=41 Participants
|
65.5 years
n=14 Participants
|
60.5 years
n=12 Participants
|
65.6 years
n=67 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=41 Participants
|
7 Participants
n=14 Participants
|
5 Participants
n=12 Participants
|
23 Participants
n=67 Participants
|
|
Sex: Female, Male
Male
|
30 Participants
n=41 Participants
|
7 Participants
n=14 Participants
|
7 Participants
n=12 Participants
|
44 Participants
n=67 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
United Kingdom
|
41 participants
n=41 Participants
|
14 participants
n=14 Participants
|
12 participants
n=12 Participants
|
67 participants
n=67 Participants
|
PRIMARY outcome
Timeframe: At baselinePopulation: Subset of Group 1a and 1b, on active chemotherapy, with lytic bone lesions identified on baseline novel MR scan, amenable to ADC measurement, and a paired baseline serum paraprotein, or paraprotein-associated immunoglobulin, level available (where measurement was unsuccessful the number analysed is lower than the overall number analysed). Group 1c, 2 and 3 participants did not have a lytic bone lesion identified on novel MR scan, and were therefore not included in the analysis.
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.
Outcome measures
| Measure |
Baseline DKK1
Baseline measurements of DKK1 (Dickkopf WNT Signaling Pathway Inhibitor 1).
|
Baseline Sclerostin
Baseline measurements of sclerostin.
|
Group 1a: New Myeloma
n=11 Participants
All patients with new myeloma at recruitment.
|
Group 1b: Relapsed Myeloma
n=3 Participants
All patients with relapsed myeloma at recruitment.
|
Baseline Sclerostin
Baseline measurements of sclerostin.
|
Baseline RANKL:OPG
Baseline measurements of the ratio between RANKL and OPG (osteoprotegerin).
|
|---|---|---|---|---|---|---|
|
Primary Outcome 1: Quantifying Tumour Burden [Correlations With Apparent Diffusion Coefficient (ADC) Measurements]
ADC vs serum paraprotein
|
—
|
—
|
-0.66 Pearson's correlation coefficient
Interval -0.99 to 0.82
|
NA Pearson's correlation coefficient
Only one data point, so not amenable to Pearson's correlation coefficient
|
—
|
—
|
|
Primary Outcome 1: Quantifying Tumour Burden [Correlations With Apparent Diffusion Coefficient (ADC) Measurements]
ADC vs serum paraprotein-associated immunoglobulin level
|
—
|
—
|
-0.28 Pearson's correlation coefficient
Interval -0.79 to 0.48
|
0.48 Pearson's correlation coefficient
Only three data points, hence 95% confidence interval cannot be reliably calculated.
|
—
|
—
|
PRIMARY outcome
Timeframe: At baselinePopulation: Population is all participants who had a novel MR scan at baseline with: i) available MY-RADS pattern of disease assessment; ii) available baseline serum paraprotein.
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.
Outcome measures
| Measure |
Baseline DKK1
n=1 Participants
Baseline measurements of DKK1 (Dickkopf WNT Signaling Pathway Inhibitor 1).
|
Baseline Sclerostin
n=1 Participants
Baseline measurements of sclerostin.
|
Group 1a: New Myeloma
n=18 Participants
All patients with new myeloma at recruitment.
|
Group 1b: Relapsed Myeloma
n=6 Participants
All patients with relapsed myeloma at recruitment.
|
Baseline Sclerostin
Baseline measurements of sclerostin.
|
Baseline RANKL:OPG
Baseline measurements of the ratio between RANKL and OPG (osteoprotegerin).
|
|---|---|---|---|---|---|---|
|
Primary Outcome 1: Quantifying Tumour Burden [Correlations With Myeloma Response Assessment and Diagnosis System (MY-RADS) Pattern of Disease]
|
5.4 grams per liter (g/L)
Standard Deviation NA
Only one data point, hence standard deviation could not be calculated
|
17.2 grams per liter (g/L)
Standard Deviation NA
Only one data point, hence standard deviation could not be calculated
|
13.1 grams per liter (g/L)
Standard Deviation 9.4
|
11.7 grams per liter (g/L)
Standard Deviation 7.8
|
—
|
—
|
PRIMARY outcome
Timeframe: At baselinePopulation: Pooled cohort of patients from Groups 1 and 2 who had measured: i) available baseline serum paraprotein; ii) by baseline bone biomarkers.
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.
Outcome measures
| Measure |
Baseline DKK1
n=28 Participants
Baseline measurements of DKK1 (Dickkopf WNT Signaling Pathway Inhibitor 1).
|
Baseline Sclerostin
n=28 Participants
Baseline measurements of sclerostin.
|
Group 1a: New Myeloma
n=28 Participants
All patients with new myeloma at recruitment.
|
Group 1b: Relapsed Myeloma
n=28 Participants
All patients with relapsed myeloma at recruitment.
|
Baseline Sclerostin
n=28 Participants
Baseline measurements of sclerostin.
|
Baseline RANKL:OPG
n=28 Participants
Baseline measurements of the ratio between RANKL and OPG (osteoprotegerin).
|
|---|---|---|---|---|---|---|
|
Primary Outcome 1: Quantifying Tumour Burden (Correlations With Bone Turnover Markers)
|
-0.18 Spearman's rank correlation coefficient
Interval -0.54 to 0.24
|
0.39 Spearman's rank correlation coefficient
Interval 0.0 to 0.68
|
0.31 Spearman's rank correlation coefficient
Interval -0.1 to 0.64
|
0.01 Spearman's rank correlation coefficient
Interval -0.41 to 0.42
|
0.23 Spearman's rank correlation coefficient
Interval -0.17 to 0.57
|
-0.02 Spearman's rank correlation coefficient
Interval -0.42 to 0.38
|
PRIMARY outcome
Timeframe: At baselinePopulation: All participants recruited at baseline from Groups 1 and 2 who had successful measurement of baseline serum P1NP.
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).
Outcome measures
| Measure |
Baseline DKK1
n=15 Participants
Baseline measurements of DKK1 (Dickkopf WNT Signaling Pathway Inhibitor 1).
|
Baseline Sclerostin
n=13 Participants
Baseline measurements of sclerostin.
|
Group 1a: New Myeloma
n=14 Participants
All patients with new myeloma at recruitment.
|
Group 1b: Relapsed Myeloma
n=11 Participants
All patients with relapsed myeloma at recruitment.
|
Baseline Sclerostin
Baseline measurements of sclerostin.
|
Baseline RANKL:OPG
Baseline measurements of the ratio between RANKL and OPG (osteoprotegerin).
|
|---|---|---|---|---|---|---|
|
Primary Outcome 2: Quantifying Bone Loss - Inter-Group Differences in Baseline Serum P1NP (Procollagen Type 1 N-terminal Propeptide)
|
39.6 microgram per litre
Standard Deviation 23.1
|
39.3 microgram per litre
Standard Deviation 23.3
|
38.6 microgram per litre
Standard Deviation 23.1
|
39.5 microgram per litre
Standard Deviation 24.0
|
—
|
—
|
PRIMARY outcome
Timeframe: At baselinePopulation: All participants recruited at baseline from Groups 1 and 2 who had successful measurement of baseline serum CTX-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 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).
Outcome measures
| Measure |
Baseline DKK1
n=15 Participants
Baseline measurements of DKK1 (Dickkopf WNT Signaling Pathway Inhibitor 1).
|
Baseline Sclerostin
n=12 Participants
Baseline measurements of sclerostin.
|
Group 1a: New Myeloma
n=13 Participants
All patients with new myeloma at recruitment.
|
Group 1b: Relapsed Myeloma
n=10 Participants
All patients with relapsed myeloma at recruitment.
|
Baseline Sclerostin
Baseline measurements of sclerostin.
|
Baseline RANKL:OPG
Baseline measurements of the ratio between RANKL and OPG (osteoprotegerin).
|
|---|---|---|---|---|---|---|
|
Primary Outcome 2: Quantifying Bone Loss - Inter-Group Differences in Baseline Serum CTX-1 (Collagen Cross-Linked C-Telopeptide Type I)
|
0.39 microgram per litre
Standard Deviation 0.32
|
0.39 microgram per litre
Standard Deviation 0.32
|
0.38 microgram per litre
Standard Deviation 0.33
|
0.40 microgram per litre
Standard Deviation 0.35
|
—
|
—
|
PRIMARY outcome
Timeframe: At baselinePopulation: All participants recruited at baseline from Groups 1 and 2 who had successful measurement of baseline serum ALP.
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).
Outcome measures
| Measure |
Baseline DKK1
n=15 Participants
Baseline measurements of DKK1 (Dickkopf WNT Signaling Pathway Inhibitor 1).
|
Baseline Sclerostin
n=13 Participants
Baseline measurements of sclerostin.
|
Group 1a: New Myeloma
n=14 Participants
All patients with new myeloma at recruitment.
|
Group 1b: Relapsed Myeloma
n=12 Participants
All patients with relapsed myeloma at recruitment.
|
Baseline Sclerostin
Baseline measurements of sclerostin.
|
Baseline RANKL:OPG
Baseline measurements of the ratio between RANKL and OPG (osteoprotegerin).
|
|---|---|---|---|---|---|---|
|
Primary Outcome 2: Quantifying Bone Loss - Inter-Group Differences in Baseline Serum ALP (Alkaline Phosphatase)
|
72.2 international units per litre
Standard Deviation 32.0
|
74.0 international units per litre
Standard Deviation 33.6
|
73.8 international units per litre
Standard Deviation 34.2
|
73.3 international units per litre
Standard Deviation 34.9
|
—
|
—
|
PRIMARY outcome
Timeframe: At baselinePopulation: All participants recruited at baseline from Groups 1 and 2 who had successful measurement of baseline serum DKK1.
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).
Outcome measures
| Measure |
Baseline DKK1
n=15 Participants
Baseline measurements of DKK1 (Dickkopf WNT Signaling Pathway Inhibitor 1).
|
Baseline Sclerostin
n=14 Participants
Baseline measurements of sclerostin.
|
Group 1a: New Myeloma
n=14 Participants
All patients with new myeloma at recruitment.
|
Group 1b: Relapsed Myeloma
n=12 Participants
All patients with relapsed myeloma at recruitment.
|
Baseline Sclerostin
Baseline measurements of sclerostin.
|
Baseline RANKL:OPG
Baseline measurements of the ratio between RANKL and OPG (osteoprotegerin).
|
|---|---|---|---|---|---|---|
|
Primary Outcome 2: Quantifying Bone Loss - Inter-Group Differences in Baseline Serum DKK1 (Dickkopf WNT Signaling Pathway Inhibitor 1)
|
3759.2 picogram per litre
Standard Deviation 3175.6
|
3924.5 picogram per litre
Standard Deviation 3568.6
|
3963.6 picogram per litre
Standard Deviation 3666.8
|
4018.9 picogram per litre
Standard Deviation 3506.5
|
—
|
—
|
PRIMARY outcome
Timeframe: At baselinePopulation: All participants recruited at baseline from Groups 1 and 2 who had successful measurement of 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).
Outcome measures
| Measure |
Baseline DKK1
n=15 Participants
Baseline measurements of DKK1 (Dickkopf WNT Signaling Pathway Inhibitor 1).
|
Baseline Sclerostin
n=14 Participants
Baseline measurements of sclerostin.
|
Group 1a: New Myeloma
n=14 Participants
All patients with new myeloma at recruitment.
|
Group 1b: Relapsed Myeloma
n=12 Participants
All patients with relapsed myeloma at recruitment.
|
Baseline Sclerostin
Baseline measurements of sclerostin.
|
Baseline RANKL:OPG
Baseline measurements of the ratio between RANKL and OPG (osteoprotegerin).
|
|---|---|---|---|---|---|---|
|
Primary Outcome 2: Quantifying Bone Loss - Inter-Group Differences in Baseline Serum Sclerostin
|
166.9 picogram per litre
Standard Deviation 86.9
|
164.9 picogram per litre
Standard Deviation 83.6
|
168.5 picogram per litre
Standard Deviation 84.1
|
165.5 picogram per litre
Standard Deviation 85.1
|
—
|
—
|
PRIMARY outcome
Timeframe: At baselinePopulation: All participants recruited at baseline from Groups 1 and 2 who had successful measurement of both baseline serum RANKL and baseline serum OPG.
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).
Outcome measures
| Measure |
Baseline DKK1
n=15 Participants
Baseline measurements of DKK1 (Dickkopf WNT Signaling Pathway Inhibitor 1).
|
Baseline Sclerostin
n=12 Participants
Baseline measurements of sclerostin.
|
Group 1a: New Myeloma
n=14 Participants
All patients with new myeloma at recruitment.
|
Group 1b: Relapsed Myeloma
n=12 Participants
All patients with relapsed myeloma at recruitment.
|
Baseline Sclerostin
Baseline measurements of sclerostin.
|
Baseline RANKL:OPG
Baseline measurements of the ratio between RANKL and OPG (osteoprotegerin).
|
|---|---|---|---|---|---|---|
|
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)
|
0.0397 RANKL (pg/L) to OPG (pg/L) ratio
Standard Deviation 0.1524
|
0.0386 RANKL (pg/L) to OPG (pg/L) ratio
Standard Deviation 0.1494
|
0.0170 RANKL (pg/L) to OPG (pg/L) ratio
Standard Deviation 0.0205
|
0.0176 RANKL (pg/L) to OPG (pg/L) ratio
Standard Deviation 0.0221
|
—
|
—
|
PRIMARY outcome
Timeframe: At baselinePopulation: Pooled population of participants from Groups 1 and 2 who had bone biomarkers measured at baseline.
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).
Outcome measures
| Measure |
Baseline DKK1
n=54 Participants
Baseline measurements of DKK1 (Dickkopf WNT Signaling Pathway Inhibitor 1).
|
Baseline Sclerostin
n=54 Participants
Baseline measurements of sclerostin.
|
Group 1a: New Myeloma
n=50 Participants
All patients with new myeloma at recruitment.
|
Group 1b: Relapsed Myeloma
n=54 Participants
All patients with relapsed myeloma at recruitment.
|
Baseline Sclerostin
n=51 Participants
Baseline measurements of sclerostin.
|
Baseline RANKL:OPG
Baseline measurements of the ratio between RANKL and OPG (osteoprotegerin).
|
|---|---|---|---|---|---|---|
|
Primary Outcome 2: Quantifying Bone Loss (Inter-Biomarker Correlations)
Baseline P1NP (Spearman's Rank Correlation Coefficient)
|
0.12 Spearman's rank correlation coefficient
Interval -0.16 to 0.39
|
0.22 Spearman's rank correlation coefficient
Interval -0.07 to 0.47
|
0.70 Spearman's rank correlation coefficient
Interval 0.51 to 0.82
|
0.37 Spearman's rank correlation coefficient
Interval 0.1 to 0.58
|
-0.10 Spearman's rank correlation coefficient
Interval -0.37 to 0.19
|
—
|
|
Primary Outcome 2: Quantifying Bone Loss (Inter-Biomarker Correlations)
Baseline CTX-1 (Spearman's Rank Correlation Coefficient)
|
0.00 Spearman's rank correlation coefficient
Interval -0.28 to 0.29
|
0.32 Spearman's rank correlation coefficient
Interval 0.03 to 0.55
|
—
|
0.25 Spearman's rank correlation coefficient
Interval -0.04 to 0.5
|
-0.21 Spearman's rank correlation coefficient
Interval -0.47 to 0.09
|
—
|
|
Primary Outcome 2: Quantifying Bone Loss (Inter-Biomarker Correlations)
Baseline ALP (Spearman's Rank Correlation Coefficient)
|
0.09 Spearman's rank correlation coefficient
Interval -0.19 to 0.36
|
-0.04 Spearman's rank correlation coefficient
Interval -0.31 to 0.24
|
—
|
—
|
-0.23 Spearman's rank correlation coefficient
Interval -0.48 to 0.06
|
—
|
|
Primary Outcome 2: Quantifying Bone Loss (Inter-Biomarker Correlations)
Baseline DKK1 (Spearman's Rank Correlation Coefficient)
|
—
|
0.11 Spearman's rank correlation coefficient
Interval -0.16 to 0.37
|
—
|
—
|
0.13 Spearman's rank correlation coefficient
Interval -0.15 to 0.39
|
—
|
|
Primary Outcome 2: Quantifying Bone Loss (Inter-Biomarker Correlations)
Baseline Sclerostin (Spearman's Rank Correlation Coefficient)
|
—
|
—
|
—
|
—
|
-0.29 Spearman's rank correlation coefficient
Interval -0.53 to -0.01
|
—
|
PRIMARY outcome
Timeframe: At baselinePopulation: Pooled population of participants from Groups 1 and 2. Where the numbers analysed are lower than the overall number of participants analysed, this reflects either failure of paired measurements for bone turnover marker and DXA and ADC, or that ADC measurements were not indicated because baseline novel MR scan did not show a lytic lesion.
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.
Outcome measures
| Measure |
Baseline DKK1
n=55 Participants
Baseline measurements of DKK1 (Dickkopf WNT Signaling Pathway Inhibitor 1).
|
Baseline Sclerostin
n=55 Participants
Baseline measurements of sclerostin.
|
Group 1a: New Myeloma
n=55 Participants
All patients with new myeloma at recruitment.
|
Group 1b: Relapsed Myeloma
n=55 Participants
All patients with relapsed myeloma at recruitment.
|
Baseline Sclerostin
n=55 Participants
Baseline measurements of sclerostin.
|
Baseline RANKL:OPG
n=55 Participants
Baseline measurements of the ratio between RANKL and OPG (osteoprotegerin).
|
|---|---|---|---|---|---|---|
|
Primary Outcome 2: Quantifying Bone Loss [Correlations Between Bone Turnover Markers, DXA (Dual-energy X-ray Absorptiometry) and ADC (Apparent Diffusion Coefficient)]
DXA BMD for L1-4 (Spearman's Rank Correlation Coefficient)
|
0.16 Spearman's rank correlation coefficient
Interval -0.12 to 0.41
|
0.25 Spearman's rank correlation coefficient
Interval -0.03 to 0.49
|
0.02 Spearman's rank correlation coefficient
Interval -0.26 to 0.29
|
0.00 Spearman's rank correlation coefficient
Interval -0.29 to 0.29
|
0.54 Spearman's rank correlation coefficient
Interval 0.31 to 0.71
|
-0.02 Spearman's rank correlation coefficient
Interval -0.3 to 0.26
|
|
Primary Outcome 2: Quantifying Bone Loss [Correlations Between Bone Turnover Markers, DXA (Dual-energy X-ray Absorptiometry) and ADC (Apparent Diffusion Coefficient)]
DXA BMD for Femoral Neck (Spearman's Rank Correlation Coefficient)
|
0.11 Spearman's rank correlation coefficient
Interval -0.17 to 0.38
|
0.19 Spearman's rank correlation coefficient
Interval -0.1 to 0.44
|
0.09 Spearman's rank correlation coefficient
Interval -0.2 to 0.37
|
0.14 Spearman's rank correlation coefficient
Interval -0.16 to 0.41
|
0.40 Spearman's rank correlation coefficient
Interval 0.13 to 0.61
|
0.10 Spearman's rank correlation coefficient
Interval -0.19 to 0.37
|
|
Primary Outcome 2: Quantifying Bone Loss [Correlations Between Bone Turnover Markers, DXA (Dual-energy X-ray Absorptiometry) and ADC (Apparent Diffusion Coefficient)]
Novel MR ADC Measurement (Spearman's Rank Correlation Coefficient)
|
-0.27 Spearman's rank correlation coefficient
Interval -0.74 to 0.37
|
-0.01 Spearman's rank correlation coefficient
Interval -0.59 to 0.58
|
0.09 Spearman's rank correlation coefficient
Interval -0.52 to 0.64
|
-0.06 Spearman's rank correlation coefficient
Insufficient number of paired baseline CTX-1 and novel MR ADC values to enable statistical detection of Spearman's Rank correlation coefficient
|
-0.42 Spearman's rank correlation coefficient
Interval -0.81 to 0.21
|
0.09 Spearman's rank correlation coefficient
Interval -0.3 to 0.26
|
PRIMARY outcome
Timeframe: At baselinePopulation: \- 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.
* 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.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: At baselinePopulation: \- 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.
* 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.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: At baselinePopulation: \- 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 as the company we contracted to undertake this was dissolved, an alternative is not available and there is no remaining budget. Therefore the results will never be possible to report.
* 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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Comparison between baseline and follow-up at 6 months.Population: Participants from Group 1 who had successfully measured paired novel MR scans and serum paraproteins, between baseline and 6-month follow-up, and with a successfully graded MY-RADS RAC, and IMWG Response Group classifications.
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.
Outcome measures
| Measure |
Baseline DKK1
n=8 Participants
Baseline measurements of DKK1 (Dickkopf WNT Signaling Pathway Inhibitor 1).
|
Baseline Sclerostin
n=9 Participants
Baseline measurements of sclerostin.
|
Group 1a: New Myeloma
n=1 Participants
All patients with new myeloma at recruitment.
|
Group 1b: Relapsed Myeloma
n=4 Participants
All patients with relapsed myeloma at recruitment.
|
Baseline Sclerostin
n=4 Participants
Baseline measurements of sclerostin.
|
Baseline RANKL:OPG
n=1 Participants
Baseline measurements of the ratio between RANKL and OPG (osteoprotegerin).
|
|---|---|---|---|---|---|---|
|
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]
MY-RADS RAC 1: Highly likely to be responding
|
0 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
3 Participants
|
0 Participants
|
|
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]
MY-RADS RAC 2: Likely to be responding
|
0 Participants
|
4 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
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]
MY-RADS RAC 3: Stable
|
8 Participants
|
3 Participants
|
1 Participants
|
3 Participants
|
1 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Comparison between baseline and follow-up at 6 monthPopulation: Participants with new or relapsed myeloma who had successfully measured paired novel MR scans at baseline and 6-month follow-up, with a successfully graded MY-RADS RAC, and a lytic bone lesion also a lytic bone lesion amenable to longitudinal calculation of % change in ADC.
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
Outcome measures
| Measure |
Baseline DKK1
Baseline measurements of DKK1 (Dickkopf WNT Signaling Pathway Inhibitor 1).
|
Baseline Sclerostin
Baseline measurements of sclerostin.
|
Group 1a: New Myeloma
n=5 Participants
All patients with new myeloma at recruitment.
|
Group 1b: Relapsed Myeloma
n=2 Participants
All patients with relapsed myeloma at recruitment.
|
Baseline Sclerostin
Baseline measurements of sclerostin.
|
Baseline RANKL:OPG
Baseline measurements of the ratio between RANKL and OPG (osteoprotegerin).
|
|---|---|---|---|---|---|---|
|
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)]
MY-RADS RAC 1: Highly likely to be responding
|
—
|
—
|
0.45 ADC Ratio (follow-up / baseline)
Standard Deviation NA
1 data point, not amenable to standard deviation calculation
|
1.40 ADC Ratio (follow-up / baseline)
Standard Deviation NA
1 data point, not amenable to standard deviation calculation
|
—
|
—
|
|
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)]
MY-RADS RAC 2: Likely to be responding
|
—
|
—
|
1.29 ADC Ratio (follow-up / baseline)
Standard Deviation 0.45
|
0.57 ADC Ratio (follow-up / baseline)
Standard Deviation NA
1 data point, not amenable to standard deviation calculation
|
—
|
—
|
|
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)]
MY-RADS RAC 3: Stable
|
—
|
—
|
1.61 ADC Ratio (follow-up / baseline)
Standard Deviation 0.45
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Comparison between baseline and follow-up at 6monthPopulation: Participants who had successfully measured paired serum paraprotein (amenable to IMWG Response Group classification) and novel MR scans (with a lytic bone lesion amenable to ADC measurement, with a successfully calculated % change in ADC) at baseline and 6-month follow-up.
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
Outcome measures
| Measure |
Baseline DKK1
Baseline measurements of DKK1 (Dickkopf WNT Signaling Pathway Inhibitor 1).
|
Baseline Sclerostin
Baseline measurements of sclerostin.
|
Group 1a: New Myeloma
n=5 Participants
All patients with new myeloma at recruitment.
|
Group 1b: Relapsed Myeloma
n=2 Participants
All patients with relapsed myeloma at recruitment.
|
Baseline Sclerostin
Baseline measurements of sclerostin.
|
Baseline RANKL:OPG
Baseline measurements of the ratio between RANKL and OPG (osteoprotegerin).
|
|---|---|---|---|---|---|---|
|
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]
IMWG: Progressive
|
—
|
—
|
1.6 ADC Ratio (follow-up / baseline)
Standard Deviation NA
Single value, not amenable to calculation of standard deviation
|
—
|
—
|
—
|
|
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]
IMWG: Partial Response
|
—
|
—
|
0.90 ADC Ratio (follow-up / baseline)
Standard Deviation 0.42
|
0.99 ADC Ratio (follow-up / baseline)
Standard Deviation 0.59
|
—
|
—
|
|
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]
IMWG: Very Good Partial Response
|
—
|
—
|
1.9 ADC Ratio (follow-up / baseline)
Standard Deviation NA
Single value, not amenable to calculation of standard deviation
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Comparison between baseline and follow-up at 6monthPopulation: Pooled cohort of participants from Groups 1 and 2 who had a IMWG response classification (responder vs non-responder) and paired serum bone turnover markers measured at baseline and follow-up.
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).
Outcome measures
| Measure |
Baseline DKK1
n=32 Participants
Baseline measurements of DKK1 (Dickkopf WNT Signaling Pathway Inhibitor 1).
|
Baseline Sclerostin
n=30 Participants
Baseline measurements of sclerostin.
|
Group 1a: New Myeloma
n=30 Participants
All patients with new myeloma at recruitment.
|
Group 1b: Relapsed Myeloma
n=30 Participants
All patients with relapsed myeloma at recruitment.
|
Baseline Sclerostin
n=31 Participants
Baseline measurements of sclerostin.
|
Baseline RANKL:OPG
n=29 Participants
Baseline measurements of the ratio between RANKL and OPG (osteoprotegerin).
|
|---|---|---|---|---|---|---|
|
Secondary Outcome 2: Detect Longitudinal Changes in Bone Microarchitecture With Therapy (% Change in Bone Turnover Markers)
IMWG Responder
|
0.85 Ratio (follow-up divided by baseline)
Standard Deviation 0.22
|
0.63 Ratio (follow-up divided by baseline)
Standard Deviation 0.40
|
0.94 Ratio (follow-up divided by baseline)
Standard Deviation 0.75
|
0.89 Ratio (follow-up divided by baseline)
Standard Deviation 0.73
|
1.22 Ratio (follow-up divided by baseline)
Standard Deviation 0.64
|
1.09 Ratio (follow-up divided by baseline)
Standard Deviation 0.81
|
|
Secondary Outcome 2: Detect Longitudinal Changes in Bone Microarchitecture With Therapy (% Change in Bone Turnover Markers)
IMWG Non-Responder
|
0.98 Ratio (follow-up divided by baseline)
Standard Deviation 0.23
|
1.15 Ratio (follow-up divided by baseline)
Standard Deviation 0.59
|
0.95 Ratio (follow-up divided by baseline)
Standard Deviation 0.21
|
1.18 Ratio (follow-up divided by baseline)
Standard Deviation 0.51
|
1.18 Ratio (follow-up divided by baseline)
Standard Deviation 0.41
|
1.51 Ratio (follow-up divided by baseline)
Standard Deviation 1.04
|
SECONDARY outcome
Timeframe: Comparison between baseline and follow-up at 6monthPopulation: Pooled population of participants from Groups 1 and 2 who had paired measurements of follow-up and baseline bone turnover markers. For some rows, the total number of participants analysed are less than the overall number of participants analysed, due to assay failure of some bone biomarkers variably on individual samples.
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.
Outcome measures
| Measure |
Baseline DKK1
n=44 Participants
Baseline measurements of DKK1 (Dickkopf WNT Signaling Pathway Inhibitor 1).
|
Baseline Sclerostin
n=43 Participants
Baseline measurements of sclerostin.
|
Group 1a: New Myeloma
n=40 Participants
All patients with new myeloma at recruitment.
|
Group 1b: Relapsed Myeloma
n=43 Participants
All patients with relapsed myeloma at recruitment.
|
Baseline Sclerostin
n=49 Participants
Baseline measurements of sclerostin.
|
Baseline RANKL:OPG
Baseline measurements of the ratio between RANKL and OPG (osteoprotegerin).
|
|---|---|---|---|---|---|---|
|
Secondary Outcome 2: Detect Longitudinal Changes in Bone Microarchitecture With Therapy (Correlations Between % Change in Bone Turnover Markers)
% Change in DKK1
|
—
|
0.13 Spearman's rank correlation coefficient
Interval -0.18 to 0.43
|
—
|
—
|
0.14 Spearman's rank correlation coefficient
Interval -0.2 to 0.44
|
—
|
|
Secondary Outcome 2: Detect Longitudinal Changes in Bone Microarchitecture With Therapy (Correlations Between % Change in Bone Turnover Markers)
% Change in P1NP
|
0.12 Spearman's rank correlation coefficient
Interval -0.2 to 0.41
|
0.32 Spearman's rank correlation coefficient
Interval 0.0 to 0.58
|
0.41 Spearman's rank correlation coefficient
Interval 0.1 to 0.64
|
0.36 Spearman's rank correlation coefficient
Interval 0.05 to 0.61
|
0.41 Spearman's rank correlation coefficient
Interval 0.09 to 0.65
|
—
|
|
Secondary Outcome 2: Detect Longitudinal Changes in Bone Microarchitecture With Therapy (Correlations Between % Change in Bone Turnover Markers)
% Change in CTX-1
|
0.11 Spearman's rank correlation coefficient
Interval -0.22 to 0.42
|
0.26 Spearman's rank correlation coefficient
Interval -0.08 to 0.54
|
—
|
0.08 Spearman's rank correlation coefficient
Interval -0.24 to 0.39
|
-0.03 Spearman's rank correlation coefficient
Interval -0.37 to 0.32
|
—
|
|
Secondary Outcome 2: Detect Longitudinal Changes in Bone Microarchitecture With Therapy (Correlations Between % Change in Bone Turnover Markers)
% Change in ALP
|
0.23 Spearman's rank correlation coefficient
Interval -0.08 to 0.51
|
-0.01 Spearman's rank correlation coefficient
Interval -0.32 to 0.31
|
—
|
—
|
-0.13 Spearman's rank correlation coefficient
Interval -0.44 to 0.21
|
—
|
|
Secondary Outcome 2: Detect Longitudinal Changes in Bone Microarchitecture With Therapy (Correlations Between % Change in Bone Turnover Markers)
% Change in Sclerostin
|
—
|
—
|
—
|
—
|
0.37 Spearman's rank correlation coefficient
Interval 0.06 to 0.62
|
—
|
SECONDARY outcome
Timeframe: Comparison between baseline and follow-up at 6monthPopulation: Participants from Groups 1 and 2 were analysed who had a paired bone turnover marker measurements available. Where the number analysed for an outcome measure is lower than the overall number of participants analysed, this is due to failure of measurement of either DXA BMD or novel MR ADC, or because ADC measurement was not indicated due to lack of a lytic bone lesion identified on MR.
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.
Outcome measures
| Measure |
Baseline DKK1
n=42 Participants
Baseline measurements of DKK1 (Dickkopf WNT Signaling Pathway Inhibitor 1).
|
Baseline Sclerostin
n=43 Participants
Baseline measurements of sclerostin.
|
Group 1a: New Myeloma
n=41 Participants
All patients with new myeloma at recruitment.
|
Group 1b: Relapsed Myeloma
n=40 Participants
All patients with relapsed myeloma at recruitment.
|
Baseline Sclerostin
n=42 Participants
Baseline measurements of sclerostin.
|
Baseline RANKL:OPG
n=38 Participants
Baseline measurements of the ratio between RANKL and OPG (osteoprotegerin).
|
|---|---|---|---|---|---|---|
|
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)]
% Change in Novel MR ADC
|
-0.50 Spearman's rank correlation coefficient
Insufficient number of participants with paired ADC measurements from paired novel MR scans, to enable statistical detection of Spearman's Rank correlation coefficient
|
-0.32 Spearman's rank correlation coefficient
Insufficient number of participants with paired ADC measurements from paired novel MR scans, to enable statistical detection of Spearman's Rank correlation coefficient
|
-0.39 Spearman's rank correlation coefficient
Insufficient number of participants with paired ADC measurements from paired novel MR scans, to enable statistical detection of Spearman's Rank correlation coefficient
|
0.31 Spearman's rank correlation coefficient
Insufficient number of participants with paired ADC measurements from paired novel MR scans, to enable statistical detection of Spearman's Rank correlation coefficient
|
-0.32 Spearman's rank correlation coefficient
Insufficient number of participants with paired ADC measurements from paired novel MR scans, to enable statistical detection of Spearman's Rank correlation coefficient
|
-0.14 Spearman's rank correlation coefficient
Insufficient number of participants with paired ADC measurements from paired novel MR scans, to enable statistical detection of Spearman's Rank correlation coefficient
|
|
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)]
% Change in DXA BMD (L1-4)
|
0.02 Spearman's rank correlation coefficient
Interval -0.29 to 0.33
|
0.02 Spearman's rank correlation coefficient
Interval -0.29 to 0.33
|
-0.12 Spearman's rank correlation coefficient
Interval -0.42 to 0.21
|
-0.10 Spearman's rank correlation coefficient
Interval -0.41 to 0.23
|
0.24 Spearman's rank correlation coefficient
Interval -0.08 to 0.51
|
-0.17 Spearman's rank correlation coefficient
Interval -0.48 to 0.16
|
|
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)]
% Change in DXA BMD (Femoral Neck)
|
-0.17 Spearman's rank correlation coefficient
Interval -0.47 to 0.16
|
-0.09 Spearman's rank correlation coefficient
Interval -0.39 to 0.24
|
-0.20 Spearman's rank correlation coefficient
Interval -0.5 to 0.13
|
-0.10 Spearman's rank correlation coefficient
Interval -0.41 to 0.24
|
0.00 Spearman's rank correlation coefficient
Interval -0.32 to 0.32
|
-0.45 Spearman's rank correlation coefficient
Interval -0.68 to -0.13
|
SECONDARY outcome
Timeframe: At baseline and six monthsPopulation: All participants from Groups 1, 2 and 3 were invited to complete EQ5D questionnaires at baseline and 6-month follow-up visits. The total number of patients analysed for each EQ5D question varied slightly depending on how many responses were received from the questionnaires.
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.
Outcome measures
| Measure |
Baseline DKK1
n=12 Participants
Baseline measurements of DKK1 (Dickkopf WNT Signaling Pathway Inhibitor 1).
|
Baseline Sclerostin
Baseline measurements of sclerostin.
|
Group 1a: New Myeloma
n=41 Participants
All patients with new myeloma at recruitment.
|
Group 1b: Relapsed Myeloma
n=14 Participants
All patients with relapsed myeloma at recruitment.
|
Baseline Sclerostin
Baseline measurements of sclerostin.
|
Baseline RANKL:OPG
Baseline measurements of the ratio between RANKL and OPG (osteoprotegerin).
|
|---|---|---|---|---|---|---|
|
Secondary Objective 3: Assess Participants' Quality of Life Throughout the Study
Baseline: Mobility
|
1.00 Scores on a scale
Standard Deviation 0.00
|
—
|
1.29 Scores on a scale
Standard Deviation 0.46
|
1.23 Scores on a scale
Standard Deviation 0.44
|
—
|
—
|
|
Secondary Objective 3: Assess Participants' Quality of Life Throughout the Study
Baseline: Health Score
|
87.9 Scores on a scale
Standard Deviation 5.9
|
—
|
72.8 Scores on a scale
Standard Deviation 22.6
|
83.9 Scores on a scale
Standard Deviation 7.7
|
—
|
—
|
|
Secondary Objective 3: Assess Participants' Quality of Life Throughout the Study
Baseline: Self-Care
|
1.00 Scores on a scale
Standard Deviation 0.00
|
—
|
1.11 Scores on a scale
Standard Deviation 0.31
|
1.08 Scores on a scale
Standard Deviation 0.28
|
—
|
—
|
|
Secondary Objective 3: Assess Participants' Quality of Life Throughout the Study
Baseline: Usual Activities
|
1.00 Scores on a scale
Standard Deviation 0.00
|
—
|
1.45 Scores on a scale
Standard Deviation 0.65
|
1.15 Scores on a scale
Standard Deviation 0.38
|
—
|
—
|
|
Secondary Objective 3: Assess Participants' Quality of Life Throughout the Study
Baseline: Pain/Discomfort
|
1.08 Scores on a scale
Standard Deviation 0.29
|
—
|
1.63 Scores on a scale
Standard Deviation 0.63
|
1.54 Scores on a scale
Standard Deviation 0.52
|
—
|
—
|
|
Secondary Objective 3: Assess Participants' Quality of Life Throughout the Study
Baseline: Anxiety/Depression
|
1.00 Scores on a scale
Standard Deviation 0.00
|
—
|
1.11 Scores on a scale
Standard Deviation 0.31
|
1.08 Scores on a scale
Standard Deviation 0.28
|
—
|
—
|
|
Secondary Objective 3: Assess Participants' Quality of Life Throughout the Study
Follow-Up: Mobility
|
—
|
—
|
1.34 Scores on a scale
Standard Deviation 0.48
|
1.33 Scores on a scale
Standard Deviation 0.49
|
—
|
—
|
|
Secondary Objective 3: Assess Participants' Quality of Life Throughout the Study
Follow-Up: Self-Care
|
—
|
—
|
1.07 Scores on a scale
Standard Deviation 0.26
|
1.17 Scores on a scale
Standard Deviation 0.39
|
—
|
—
|
|
Secondary Objective 3: Assess Participants' Quality of Life Throughout the Study
Follow-Up: Usual Activities
|
—
|
—
|
1.38 Scores on a scale
Standard Deviation 0.49
|
1.25 Scores on a scale
Standard Deviation 0.45
|
—
|
—
|
|
Secondary Objective 3: Assess Participants' Quality of Life Throughout the Study
Follow-Up: Pain/Discomfort
|
—
|
—
|
1.59 Scores on a scale
Standard Deviation 0.63
|
1.42 Scores on a scale
Standard Deviation 0.51
|
—
|
—
|
|
Secondary Objective 3: Assess Participants' Quality of Life Throughout the Study
Follow-Up: Anxiety/Depression
|
—
|
—
|
1.21 Scores on a scale
Standard Deviation 0.41
|
1.08 Scores on a scale
Standard Deviation 0.29
|
—
|
—
|
|
Secondary Objective 3: Assess Participants' Quality of Life Throughout the Study
Follow-Up: Health Score
|
—
|
—
|
75.1 Scores on a scale
Standard Deviation 20.5
|
79.0 Scores on a scale
Standard Deviation 15.6
|
—
|
—
|
SECONDARY outcome
Timeframe: At baseline and six monthsPopulation: Baseline: all participants from Groups 1,2,3 were invited for novel MR scan, and only participants from Groups 1 and 2 were invited for DXA Follow-up: only participants from Groups 1 and 2 were invited for a novel MR scan and also a DXA.
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)
Outcome measures
| Measure |
Baseline DKK1
n=12 Participants
Baseline measurements of DKK1 (Dickkopf WNT Signaling Pathway Inhibitor 1).
|
Baseline Sclerostin
Baseline measurements of sclerostin.
|
Group 1a: New Myeloma
n=41 Participants
All patients with new myeloma at recruitment.
|
Group 1b: Relapsed Myeloma
n=14 Participants
All patients with relapsed myeloma at recruitment.
|
Baseline Sclerostin
Baseline measurements of sclerostin.
|
Baseline RANKL:OPG
Baseline measurements of the ratio between RANKL and OPG (osteoprotegerin).
|
|---|---|---|---|---|---|---|
|
Secondary Outcome 4: Assess Participants' Experience of Novel Magnetic Resonance (MR) and Dual-energy X-ray Absorptiometry (DXA) Scans
Baseline novel MR scan experience: Q1 = Overall Experience
|
2.13 Score on a scale (see description above)
Standard Deviation 0.92
|
—
|
2.10 Score on a scale (see description above)
Standard Deviation 0.91
|
2.10 Score on a scale (see description above)
Standard Deviation 0.93
|
—
|
—
|
|
Secondary Outcome 4: Assess Participants' Experience of Novel Magnetic Resonance (MR) and Dual-energy X-ray Absorptiometry (DXA) Scans
Baseline novel MR scan experience: Q2 = Adverse Effects
|
0.33 Score on a scale (see description above)
Standard Deviation 0.47
|
—
|
0.30 Score on a scale (see description above)
Standard Deviation 0.46
|
0.31 Score on a scale (see description above)
Standard Deviation 0.47
|
—
|
—
|
|
Secondary Outcome 4: Assess Participants' Experience of Novel Magnetic Resonance (MR) and Dual-energy X-ray Absorptiometry (DXA) Scans
Baseline novel MR scan experience: Q3 = Length of Time
|
1.40 Score on a scale (see description above)
Standard Deviation 0.50
|
—
|
1.39 Score on a scale (see description above)
Standard Deviation 0.49
|
1.40 Score on a scale (see description above)
Standard Deviation 0.49
|
—
|
—
|
|
Secondary Outcome 4: Assess Participants' Experience of Novel Magnetic Resonance (MR) and Dual-energy X-ray Absorptiometry (DXA) Scans
Baseline novel MR scan experience: Q4 = Pain/Discomfort
|
1.73 Score on a scale (see description above)
Standard Deviation 0.89
|
—
|
1.75 Score on a scale (see description above)
Standard Deviation 0.86
|
1.74 Score on a scale (see description above)
Standard Deviation 0.87
|
—
|
—
|
|
Secondary Outcome 4: Assess Participants' Experience of Novel Magnetic Resonance (MR) and Dual-energy X-ray Absorptiometry (DXA) Scans
Baseline novel MR scan experience: Q5 = How Likely to Re-participate
|
3.34 Score on a scale (see description above)
Standard Deviation 0.96
|
—
|
3.34 Score on a scale (see description above)
Standard Deviation 0.91
|
3.36 Score on a scale (see description above)
Standard Deviation 0.92
|
—
|
—
|
|
Secondary Outcome 4: Assess Participants' Experience of Novel Magnetic Resonance (MR) and Dual-energy X-ray Absorptiometry (DXA) Scans
Baseline novel MR scan experience: Q6 = How Similar to Expectations
|
1.00 Score on a scale (see description above)
Standard Deviation 0.00
|
—
|
1.00 Score on a scale (see description above)
Standard Deviation 0.00
|
1.00 Score on a scale (see description above)
Standard Deviation 0.00
|
—
|
—
|
|
Secondary Outcome 4: Assess Participants' Experience of Novel Magnetic Resonance (MR) and Dual-energy X-ray Absorptiometry (DXA) Scans
Baseline novel MR scan experience: Q7 = Comfort with Staff
|
1.00 Score on a scale (see description above)
Standard Deviation 0.00
|
—
|
1.00 Score on a scale (see description above)
Standard Deviation 0.00
|
1.00 Score on a scale (see description above)
Standard Deviation 0.00
|
—
|
—
|
|
Secondary Outcome 4: Assess Participants' Experience of Novel Magnetic Resonance (MR) and Dual-energy X-ray Absorptiometry (DXA) Scans
Follow-up novel MR scan experience: Q1 = Overall Experience
|
—
|
—
|
2.17 Score on a scale (see description above)
Standard Deviation 1.07
|
2.20 Score on a scale (see description above)
Standard Deviation 1.11
|
—
|
—
|
|
Secondary Outcome 4: Assess Participants' Experience of Novel Magnetic Resonance (MR) and Dual-energy X-ray Absorptiometry (DXA) Scans
Follow-up novel MR scan experience: Q2 = Adverse Effects
|
—
|
—
|
0.27 Score on a scale (see description above)
Standard Deviation 0.45
|
0.28 Score on a scale (see description above)
Standard Deviation 0.45
|
—
|
—
|
|
Secondary Outcome 4: Assess Participants' Experience of Novel Magnetic Resonance (MR) and Dual-energy X-ray Absorptiometry (DXA) Scans
Follow-up novel MR scan experience: Q3 = Length of Time
|
—
|
—
|
1.30 Score on a scale (see description above)
Standard Deviation 0.46
|
1.33 Score on a scale (see description above)
Standard Deviation 0.48
|
—
|
—
|
|
Secondary Outcome 4: Assess Participants' Experience of Novel Magnetic Resonance (MR) and Dual-energy X-ray Absorptiometry (DXA) Scans
Follow-up novel MR scan experience: Q4 = Pain/Discomfort
|
—
|
—
|
1.44 Score on a scale (see description above)
Standard Deviation 0.71
|
1.48 Score on a scale (see description above)
Standard Deviation 0.82
|
—
|
—
|
|
Secondary Outcome 4: Assess Participants' Experience of Novel Magnetic Resonance (MR) and Dual-energy X-ray Absorptiometry (DXA) Scans
Follow-up novel MR scan experience: Q5 = How Likely to Re-participate
|
—
|
—
|
3.29 Score on a scale (see description above)
Standard Deviation 1.05
|
3.33 Score on a scale (see description above)
Standard Deviation 1.05
|
—
|
—
|
|
Secondary Outcome 4: Assess Participants' Experience of Novel Magnetic Resonance (MR) and Dual-energy X-ray Absorptiometry (DXA) Scans
Follow-up novel MR scan experience: Q6 = How Similar to Expectations
|
—
|
—
|
1.00 Score on a scale (see description above)
Standard Deviation 0.00
|
1.00 Score on a scale (see description above)
Standard Deviation 0.00
|
—
|
—
|
|
Secondary Outcome 4: Assess Participants' Experience of Novel Magnetic Resonance (MR) and Dual-energy X-ray Absorptiometry (DXA) Scans
Follow-up novel MR scan experience: Q7 = Comfort with Staff
|
—
|
—
|
1.00 Score on a scale (see description above)
Standard Deviation 0.00
|
0.98 Score on a scale (see description above)
Standard Deviation 0.16
|
—
|
—
|
|
Secondary Outcome 4: Assess Participants' Experience of Novel Magnetic Resonance (MR) and Dual-energy X-ray Absorptiometry (DXA) Scans
Baseline DXA scan experience: Q1 = Overall Experience
|
—
|
—
|
1.58 Score on a scale (see description above)
Standard Deviation 0.72
|
1.61 Score on a scale (see description above)
Standard Deviation 0.72
|
—
|
—
|
|
Secondary Outcome 4: Assess Participants' Experience of Novel Magnetic Resonance (MR) and Dual-energy X-ray Absorptiometry (DXA) Scans
Baseline DXA scan experience: Q2 = Adverse Effects
|
—
|
—
|
0.11 Score on a scale (see description above)
Standard Deviation 0.32
|
0.12 Score on a scale (see description above)
Standard Deviation 0.33
|
—
|
—
|
|
Secondary Outcome 4: Assess Participants' Experience of Novel Magnetic Resonance (MR) and Dual-energy X-ray Absorptiometry (DXA) Scans
Baseline DXA scan experience: Q3 = Length of Time
|
—
|
—
|
1.00 Score on a scale (see description above)
Standard Deviation 0.00
|
1.00 Score on a scale (see description above)
Standard Deviation 0.00
|
—
|
—
|
|
Secondary Outcome 4: Assess Participants' Experience of Novel Magnetic Resonance (MR) and Dual-energy X-ray Absorptiometry (DXA) Scans
Baseline DXA scan experience: Q4 = Pain/Discomfort
|
—
|
—
|
1.17 Score on a scale (see description above)
Standard Deviation 0.43
|
1.16 Score on a scale (see description above)
Standard Deviation 0.42
|
—
|
—
|
|
Secondary Outcome 4: Assess Participants' Experience of Novel Magnetic Resonance (MR) and Dual-energy X-ray Absorptiometry (DXA) Scans
Baseline DXA scan experience: Q5 = How Likely to Re-participate
|
—
|
—
|
3.51 Score on a scale (see description above)
Standard Deviation 0.85
|
3.53 Score on a scale (see description above)
Standard Deviation 0.83
|
—
|
—
|
|
Secondary Outcome 4: Assess Participants' Experience of Novel Magnetic Resonance (MR) and Dual-energy X-ray Absorptiometry (DXA) Scans
Baseline DXA scan experience: Q6 = How Similar to Expectations
|
—
|
—
|
0.98 Score on a scale (see description above)
Standard Deviation 0.14
|
0.98 Score on a scale (see description above)
Standard Deviation 0.14
|
—
|
—
|
|
Secondary Outcome 4: Assess Participants' Experience of Novel Magnetic Resonance (MR) and Dual-energy X-ray Absorptiometry (DXA) Scans
Baseline DXA scan experience: Q7 = Comfort with Staff
|
—
|
—
|
1.00 Score on a scale (see description above)
Standard Deviation 0.00
|
1.00 Score on a scale (see description above)
Standard Deviation 0.00
|
—
|
—
|
|
Secondary Outcome 4: Assess Participants' Experience of Novel Magnetic Resonance (MR) and Dual-energy X-ray Absorptiometry (DXA) Scans
Follow-up DXA scan experience: Q1 = Overall Experience
|
—
|
—
|
1.65 Score on a scale (see description above)
Standard Deviation 0.75
|
1.71 Score on a scale (see description above)
Standard Deviation 0.83
|
—
|
—
|
|
Secondary Outcome 4: Assess Participants' Experience of Novel Magnetic Resonance (MR) and Dual-energy X-ray Absorptiometry (DXA) Scans
Follow-up DXA scan experience: Q2 = Adverse Effects
|
—
|
—
|
0.09 Score on a scale (see description above)
Standard Deviation 0.29
|
0.10 Score on a scale (see description above)
Standard Deviation 0.30
|
—
|
—
|
|
Secondary Outcome 4: Assess Participants' Experience of Novel Magnetic Resonance (MR) and Dual-energy X-ray Absorptiometry (DXA) Scans
Follow-up DXA scan experience: Q3 = Length of Time
|
—
|
—
|
1.05 Score on a scale (see description above)
Standard Deviation 0.21
|
1.07 Score on a scale (see description above)
Standard Deviation 0.26
|
—
|
—
|
|
Secondary Outcome 4: Assess Participants' Experience of Novel Magnetic Resonance (MR) and Dual-energy X-ray Absorptiometry (DXA) Scans
Follow-up DXA scan experience: Q4 = Pain/Discomfort
|
—
|
—
|
1.12 Score on a scale (see description above)
Standard Deviation 0.32
|
1.19 Score on a scale (see description above)
Standard Deviation 0.55
|
—
|
—
|
|
Secondary Outcome 4: Assess Participants' Experience of Novel Magnetic Resonance (MR) and Dual-energy X-ray Absorptiometry (DXA) Scans
Follow-up DXA scan experience: Q5 = How Likely to Re-participate
|
—
|
—
|
3.63 Score on a scale (see description above)
Standard Deviation 0.85
|
3.67 Score on a scale (see description above)
Standard Deviation 0.85
|
—
|
—
|
|
Secondary Outcome 4: Assess Participants' Experience of Novel Magnetic Resonance (MR) and Dual-energy X-ray Absorptiometry (DXA) Scans
Follow-up DXA scan experience: Q6 = How Similar to Expectations
|
—
|
—
|
1.00 Score on a scale (see description above)
Standard Deviation 1.00
|
1.00 Score on a scale (see description above)
Standard Deviation 0.00
|
—
|
—
|
|
Secondary Outcome 4: Assess Participants' Experience of Novel Magnetic Resonance (MR) and Dual-energy X-ray Absorptiometry (DXA) Scans
Follow-up DXA scan experience: Q7 = Comfort with Staff
|
—
|
—
|
1.00 Score on a scale (see description above)
Standard Deviation 1.00
|
0.98 Score on a scale (see description above)
Standard Deviation 0.15
|
—
|
—
|
POST_HOC outcome
Timeframe: At baselinePopulation: Analysis included patients from Groups 1a and 1b who had a novel MR scan at baseline, with a lytic bone lesion identified amenable to ADC measurement.
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).
Outcome measures
| Measure |
Baseline DKK1
Baseline measurements of DKK1 (Dickkopf WNT Signaling Pathway Inhibitor 1).
|
Baseline Sclerostin
Baseline measurements of sclerostin.
|
Group 1a: New Myeloma
n=11 Participants
All patients with new myeloma at recruitment.
|
Group 1b: Relapsed Myeloma
n=6 Participants
All patients with relapsed myeloma at recruitment.
|
Baseline Sclerostin
Baseline measurements of sclerostin.
|
Baseline RANKL:OPG
Baseline measurements of the ratio between RANKL and OPG (osteoprotegerin).
|
|---|---|---|---|---|---|---|
|
Post-Hoc Analysis: Relationship Between Intercurrent Chemotherapy and Baseline Magnetic Resonance (MR) Apparent Diffusion Coefficient (ADC) Measurements
Baseline ADC: Ongoing Chemotherapy
|
—
|
—
|
1084.5 s/mm^2 (ADC measurement unit)
Standard Deviation 432.5
|
1215.3 s/mm^2 (ADC measurement unit)
Standard Deviation 319.4
|
—
|
—
|
|
Post-Hoc Analysis: Relationship Between Intercurrent Chemotherapy and Baseline Magnetic Resonance (MR) Apparent Diffusion Coefficient (ADC) Measurements
Baseline ADC: Recent (<1yr) Chemotherapy
|
—
|
—
|
—
|
751.7 s/mm^2 (ADC measurement unit)
Standard Deviation 134.8
|
—
|
—
|
|
Post-Hoc Analysis: Relationship Between Intercurrent Chemotherapy and Baseline Magnetic Resonance (MR) Apparent Diffusion Coefficient (ADC) Measurements
Baseline ADC: Never Chemotherapy
|
—
|
—
|
547.5 s/mm^2 (ADC measurement unit)
Standard Deviation 74.2
|
—
|
—
|
—
|
POST_HOC outcome
Timeframe: At follow-upPopulation: Analysis included patients from Groups 1a and 1b who had a novel MR scan at follow-up, with a lytic bone lesion identified amenable to ADC measurement.
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).
Outcome measures
| Measure |
Baseline DKK1
Baseline measurements of DKK1 (Dickkopf WNT Signaling Pathway Inhibitor 1).
|
Baseline Sclerostin
Baseline measurements of sclerostin.
|
Group 1a: New Myeloma
n=6 Participants
All patients with new myeloma at recruitment.
|
Group 1b: Relapsed Myeloma
n=4 Participants
All patients with relapsed myeloma at recruitment.
|
Baseline Sclerostin
Baseline measurements of sclerostin.
|
Baseline RANKL:OPG
Baseline measurements of the ratio between RANKL and OPG (osteoprotegerin).
|
|---|---|---|---|---|---|---|
|
Post-Hoc Analysis: Relationship Between Intercurrent Chemotherapy and Follow-Up Magnetic Resonance (MR) Apparent Diffusion Coefficient (ADC) Measurements
Follow-Up ADC: Ongoing Chemotherapy
|
—
|
—
|
1875 s/mm^2 (ADC measurement unit)
Standard Deviation 205
|
1415 s/mm^2 (ADC measurement unit)
Standard Deviation 968.7
|
—
|
—
|
|
Post-Hoc Analysis: Relationship Between Intercurrent Chemotherapy and Follow-Up Magnetic Resonance (MR) Apparent Diffusion Coefficient (ADC) Measurements
Follow-Up ADC: Recent (<1yr) Chemotherapy
|
—
|
—
|
1252.3 s/mm^2 (ADC measurement unit)
Standard Deviation 634.7
|
900 s/mm^2 (ADC measurement unit)
|
—
|
—
|
|
Post-Hoc Analysis: Relationship Between Intercurrent Chemotherapy and Follow-Up Magnetic Resonance (MR) Apparent Diffusion Coefficient (ADC) Measurements
Follow-Up ADC: Historic Chemotherapy (>1yr)
|
—
|
—
|
—
|
648 s/mm^2 (ADC measurement unit)
|
—
|
—
|
Adverse Events
Group 1- Myeloma
Group 2- MGUS
Group 3- Healthy Volunteers
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place