Early Treatment Response Assessment with Sequential Whole Body Magnetic Resonance Imaging in Patients with Newly Diagnosed Multiple Myeloma

Introduction: Modern imaging techniques are essential for the diagnosis of myeloma bone disease in patients with newly diagnosed multiple myeloma (NDMM). Currently, sensitive methods, such as whole body low dose computed tomography and whole body magnetic resonance imaging (WBMRI), are often being used to evaluate patients at first presentation, in order to differentiate symptomatic from asymptomatic disease. Although consecutive imaging assessment is considered as a standard of care for patients with plasmacytomas, the role of imaging re-evaluation at fixed timepoints for all symptomatic patients under anti-myeloma treatment is rather unclear.

Methods: In this prospective cohort study, we enrolled sequentially patients withNDMM, who underwent WBMRI at the time of diagnosis and two months after treatment initiation, regardless of disease status or clinical symptoms. The baseline WBMRI was performed before the initiation of any anti-myeloma or antiresorptive treatment. All participants provided written informed consent and the study was approved by the institutional review board.

Results: Seventy-eight patients with NDMM were included, with a median age of 68 years (range 32-89), whereas 32.1% were females. All patients underwent WBMRI at baseline with the following distribution of imaging patterns: 38 (48.7%) patients had focal pattern, 19 (24.4%) normal, 9 (11.5%) variegated, 8 (10.3%) diffuse and 4 (5.1%) had distinct foci of both diffuse and focal pattern. Baseline WMBRI revealed paramedullary disease (PMD) in 17 (21.8%) patients and fractures in 21 (26.9%) patients. 43 patients (55.1%) received anti-CD38-based upfront treatment, 17 patients (21.8%) received bortezomib-lenalidomide-dexamethasone (VRd), and 18 patients (23.1%) received other regimens.

Two months after treatment initiation, 73 patients (93.6%) had achieved at least partial remission (PR). Median time to best response was 2.7 months (range 0.8-17.8); 7 CR or better (9.0%), 44 VGPR (56.4%), 22 PR (28.2%), 1 MR (1.3%) and 1 SD (1.3%). Imaging responses assessed according to the second WBMRI were as follows: 13 (16.7%) CR, 31 (39.7%) nearCR (nCR), 11 (14.1%) PR and 3 (3.8%) SD. Out of the 17 patients with PMD at baseline, all but one responded (94.1%). During a median follow-up of 16.5 months (range 3-27), 3 patients (3.8%) progressed and 2 (2.6%) died. One disease progression was identified at the second WBMRI, before documented hematological myeloma progression or clinical deterioration. Median survival times were not reached.

Interestingly, nCR WBMRI responses were associated with VGPR serum responses (OR 2.72, 95%CI: 1.05-7.49, p=0.049). There was no association between type of first line of therapy and WBMRI response. Although ISS stage at baseline was associated with serum response (Fisher's, p=0.025), it was not associated with WBMRI response (p=0.646). Imaging pattern at baseline was significantly associated with imaging PR or better on WBMRI (Fisher's, p=0.022) but not with hematologic response (Fisher's, p=0.697).

Overall, 21 (26.9%) patients presented with fractures at baseline. Importantly, 12 patients (15.4%) were diagnosed with new fractures at the time of the second WBMRI; seven (8.9%) were recurrent events. These new fractures were not evaluated as progressive disease, since there were no new osteolyses or plasmacytomas and the disease was in hematologic response. These skeletal-related events (SREs) were attributed to the extended myeloma bone disease burden at baseline that receded rapidly with treatment. Interestingly, the presence of fractures identified by WBMRI at baseline were statistically significantly associated with new occurrences of fractures at the second WBMRI (Fisher's, p=0.021). Specifically, patients with a fracture at baseline had 5.02 (95% CI: 1.37, 19.99) times the odds to present with a new one at the second WBMRI. Imaging pattern at baseline was not associated with the occurrence of a new fracture at the time of the second MRI.

Conclusion:

Sequential imaging assessment with WBMRI at baseline and after two months of treatment may complement hematological evaluation of disease response in patients with NDMM. A WBMRI re-evaluation may identify early signs of disease refractoriness and new SREs that have direct implications in patient management and may prevent clinical deterioration. Longer follow-up will reveal the potential prognostic value of sequential WBMRI.

Ntanasis-Stathopoulos:Janssen-Cilag: Honoraria; AstraZeneca: Honoraria; Cellectar Biosciences: Research Funding. Gavriatopoulou:Swixx: Honoraria; Takeda: Consultancy, Honoraria; Genesis Pharma: Honoraria; Karyopharm: Consultancy; Integris: Honoraria; Janssen Cilag: Honoraria; GSK: Consultancy, Honoraria; Cellectar Biosciences: Research Funding; BMS: Research Funding; AbbVie: Honoraria; Beigene: Research Funding; Amgen: Consultancy. Fotiou:Sanofi: Honoraria; Janssen: Honoraria. Migkou:Janssen Cilag: Honoraria; GlaxoSmithKline: Honoraria. Kastritis:Prothena: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genesis Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria. Dimopoulos:Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; Menarini: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; BeiGene Inc: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; Swixx: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen, Abbvie, Takeda, Beigene, BMS, GSK, Janssen, Menarini, Regeneron, Sanofi: Other: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events. Terpos:Menarini/Stemline: Honoraria; Janssen: Honoraria, Research Funding; GSK: Honoraria, Research Funding; EUSA Pharma: Honoraria, Other: Travel expenses; AstraZeneca: Honoraria, Other: Travel expenses; BMS: Honoraria; Amgen: Honoraria, Other: Travel expenses, Research Funding; Pfizer: Honoraria; Sanofi: Honoraria, Other: Travel expenses, Research Funding; Takeda: Honoraria, Other: Travel expenses, Research Funding; Novartis: Honoraria; Antengene: Honoraria, Research Funding; Swixx: Honoraria.