Sequential Whole Body Low Dose CTs in Patients with Smoldering Multiple Myeloma Identify Early Progression and May Improve Patient Outcomes
Authors: Gavriatopoulou Maria , Koutoulidis Vassilis , Ntanasis-Stathopoulos Ioannis , Malandrakis Panagiotis , Douka Maria , Spiliopoulou Vasiliki , Filippatos Charalampos , Fotiou Despina , Migkou Magdalini , Kanellias Nikolaos , Eleutherakis-Papaiakovou Evangelos , Kastritis Efstathios , Terpos Evangelos , Dimopoulos Meletios A. , Moulopoulos Lia-Angela 
Published: December 2024

Introduction
Whole-body low dose CT (WBLDCT) has been established as the gold standard for detecting myeloma bone disease (MBD) and it has been incorporated in the surveillance of patients with smoldering multiple myeloma (sMM). Herein, we evaluated the role of sequential WBLDCT assessments in the early identification of patients who progress to symptomatic disease.
Methods
Consecutive patients diagnosed with SMM based on the 2003 IMWG definition of sMM were serially assessed with WBLDCT. The assessments were performed at baseline, 1- year post diagnosis and every 1 year thereafter. The patients enrolled in the study were those who had at least two consecutive CT assessments at the above described time points and were followed with hematologic, biochemical and immunological tests every 3 months for the first two years, and every 6 months thereafter. The date of last follow up was July 1st, 2024.
Results
We prospectively evaluated 113 patients with sMM, with a median age at diagnosis of 60 years (range 35-85 years), whereas 53.1% were female. The median number of WBLDCT exams performed was 3 (range 1-6). The distribution of the patients according to the IMWG 2/20/20 risk stratification model was 36.3% low risk, 33.6% low-intermediate risk, 24.0% intermediate risk, and 4.4% high risk.
Over a median follow-up period of 8.81 years (IQR 7.3-10.7 years), 41 patients (36.3%) progressed, according to the CRAB-SLiM criteria. Importantly, 11 out of 41 patients (26.8%) progressed solely with bone lesions that were detected on WBLDCT. The median follow-up period was 8.82 years for bone-only progressors compared to 10.05 years for other progressors. Within this subgroup, 45.5% were in the intermediate-risk stage, 9.1% in the high-risk stage, and only 9.1% were in the low-risk stage.
No significant differences were noted with regards to baseline hemoglobin, albumin, b2 microglobulin, FLCs, bone marrow infiltration, and other baseline patient characteristics between the bone-only and the other progressors. The other 30 patients progressed with anemia (n=6), bone marrow infiltration &gt;60% (n=3), abnormal free light chain ratio &gt;100 (n=3), while 19 patients progressed with more than one CRAB/SLiM events (n=11 with two criteria, n=5 with three, n=2 with four).
The median time to progression (TTP) from asymptomatic to symptomatic disease for all 113 patients was 14.8 years (95% CI: 10.0, NA). For those who actually progressed, the median TTP was 2.95 years (95% CI: 2.46, 4.39). In the subgroup of patients who progressed with bone lesions only, the median TTP was 2.59 years (95% CI: 1.96, NA), compared to 3.02 years (95% CI: 1.96, NA) for other progressors. There was no statistically significant difference between the two progressor subgroups [p=0.244].
At the time of progression to symptomatic disease, bone marrow infiltration had significantly increased compared to baseline for bone-only progressors (25.5% versus 44.4%, p = 0.028). The distribution per ISS stage at the time of progression was 56.1% for stage 1, 36.6% for stage 2, and 7.3% for stage 3 for all patients who progressed and it was 72.7% for stage 1 and 27.3% for stage 2 for those who progressed only with bone lesions. The R- ISS stage distribution was 46.3%, 43.9%, and 9.8% for stage 1, 2, and 3, respectively, for all patients who progressed, while for the bone progressors it was 63.6% and 36.4% for stage 1 and 2, respectively. There were no differences in ISS and R-ISS distributions between the two subgroups.
All patients began antimyeloma treatment immediately after diagnosis of symptomatic disease. 19 patients experienced disease progression at first-line treatment: 3 (27.3%) from the bone-only subgroup and 16 (53.3%) from the others. The median progression-free survival (PFS) for the 41 patients with symptomatic MM was 6.66 years (2.66, NA). For bone-only progressors, the median PFS was not reached and it was 3.43 years (2.10, NA) for the other progressors from sMM to MM (p=0.113). Overall, there were three deaths: 2 among the patients who progressed to MM (1 MM-related) and 1 among the non-progressors. None of the patients who died had progressed with isolated bone involvement.
Conclusion
Sequential imaging assessment with annual WBLDCT in patients with sMM enabled early diagnosis of MBD in approximately 10%. Early detection of myeloma progression and prompt initiation of anti-myeloma treatment may prevent end organ damage and improve patient outcomes.