Whole-body MRI quantitative biomarkers are associated significantly with treatment response in patients with newly diagnosed symptomatic multiple myeloma following bortezomib induction

Abstract

Objectives: To evaluate whole-body MRI (WB-MRI) parameters significantly associated with treatment response in multiple myeloma (MM).

Methods: Twenty-one MM patients underwent WB-MRI at diagnosis and after two cycles of chemotherapy. Scans acquired at 3.0 T included T2, diffusion-weighted-imaging (DWI) and mDixon pre- and post-contrast. Twenty focal lesions (FLs) matched on DWI and post-contrast mDixon were selected for each time point. Estimated tumour volume (eTV), apparent diffusion coefficient (ADC), enhancement ratio (ER) and signal fat fraction (sFF) were derived. Clinical treatment response to chemotherapy was assessed using conventional criteria. Significance of temporal parameter change was assessed by the paired t test and receiver operating characteristics/area under the curve (AUC) analysis was performed. Parameter repeatability was assessed by interclass correlation (ICC) and Bland-Altman analysis of 10 healthy volunteers scanned at two time points.

Results: Fifteen of 21 patients responded to treatment. Of 254 FLs analysed, sFF (p < 0.0001) and ADC (p = 0.001) significantly increased in responders but not non-responders. eTV significantly decreased in 19/21 cases. Focal lesion sFF was the best discriminator of treatment response (AUC 1.0). Bone sFF repeatability was excellent (ICC 0.98) and better than bone ADC (ICC 0.47).

Conclusion: WB-MRI derived focal lesion sFF shows promise as an imaging biomarker of treatment response in newly diagnosed MM.

Key points: • Bone signal fat fraction using mDixon is a robust quantifiable parameter • Fat fraction and ADC significantly increase in myeloma lesions responding to treatment • Bone lesion fat fraction is the best discriminator of myeloma treatment response.

Keywords: Bortezomib; MRI; Multiple myeloma; Response monitoring; Whole body.

Fig. 1

Patient selection and recruitment flowchart

Fig. 2

Box and whisker plots of temporal changes of a signal fat fraction (sFF), b apparent diffusion coefficient (ADC), c estimated tumour volume (eTV) and d enhancement ratio (ER) in responder and non-responder groups. The boundaries of the box show 25th and 75th percentiles, and the line within the box is the median. Whiskers show 10th and 90th percentiles. Means (+) and outliers (•) are shown. Each point represents a patient

Fig. 3

Representative images of the whole-body MRI scan of a 52-year-old female participant prior to (a1–c1) and following two cycles (a2–c2) of induction PAD (bortezomib, doxorubicin, dexamethasone) chemotherapy. a1, a2 coronal signal fat fraction map; b1, b2 coronal post-contrast water-only mDixon; c1, c2 Axial b ₁₀₀₀ diffusion-weighted MRI images depicting a focal lesion at the level of L3 vertebral body on the right side (arrows). Compared to baseline and following two cycles of treatment there were a 42.7% reduction in eTV, 51.7% reduction in ER, 25% increase in ADC and 80% increase in FF of the focal lesion

Fig. 4

Per patient changes of signal fat fraction (sFF), apparent diffusion coefficient (ADC), estimated tumour volume (eTV) and enhancement ratio (ER) between baseline and post-2nd cycle scans. Subject is a 46-year-old male participant who achieved complete response (CR) after induction chemotherapy with PAD (bortezomib, doxorubicin, dexamethasone). Each data point is representative of a focal lesion at baseline and post-2nd cycle scan. Significant defined as p < 0.05

Fig. 5

Per patient changes of signal fat fraction (sFF), apparent diffusion coefficient (ADC), estimated tumour volume (eTV) and enhancement ratio (ER) between baseline and post-2nd cycle scans. Subject is a 55-year-old male participant who achieved minimal response (MR) after induction chemotherapy with PAD (bortezomib, doxorubicin, dexamethasone). Each data point is representative of a focal lesion at baseline and post-2nd cycle scan. Significant defined as p < 0.05

Fig. 6

Bland–Altman plots of signal fat fraction (sFF) and apparent diffusion coefficient (ADC). For sFF, 95% limits of agreement were −0.085 to 0.105 (a.u.) with standard of bias of 0.048. For ADC, 95% limits of agreement were −134.3 to 162.1 (mm²/s × 10⁻⁶) with standard of bias of 75.61. There is a wider dispersion of values for ADC and mean differences between two measurements in each subject are closer to zero for sFF compared to ADC. The dotted lines represent 95% level of agreement