The importance of MRI in diagnostic workup of smoldering multiple myeloma Free

Background In 2014, the International Myeloma Working Group (IMWG) revised the diagnostic criteria for multiple myeloma (MM), incorporating biomarkers summarized by the acronym SLiM. Among these, the presence of >1 focal lesion on magnetic resonance imaging (MRI) was designated a myeloma-defining event. The National Comprehensive Cancer Network (NCCN) recommends a whole-body (WB) MRI without contrast to discern smoldering MM (SMM) from MM if a CT or FDG PET/CT is negative. Therefore, the majority of patients with presumed SMM should undergo MRI. Failure to include a screening MRI in the diagnostic workup of SMM could lead to a missed diagnosis of MM, potentially delaying treatment or obscuring the true risk of progression.

Objective To assess the prevalence of whole-body/spine MRI use in the evaluation of patients with SMM and to determine the frequency in which MRI findings lead to reclassification from SMM to active MM.

Methods We conducted a retrospective review of medical records of patients who underwent screening for two IRB approved SMM clinical trials (NCT01572480 and NCT04933539). Patients were referred from outside institutions with a presumed diagnosis of SMM to the NIH Clinical Center between April 2014 and December 2024. First, referral records were reviewed to identify whether an MRI had been performed by the referring physician prior to our institutional clinical assessment. Second, institutional records were reviewed, irrespective of prior radiographic imaging, to identify presumed SMM patients who underwent a whole-spine (SP) or WB MRI at NIH. MRIs were considered positive for active MM if they identified >1 lesions ≥5 mm consistent with the Myeloma Response Assessment and Diagnosis System (MY-RADS) guidelines including having T1 hypointense and STIR hyperintense signal features within detected lesions.

Results Medical records from 134 SMM referrals were reviewed. Most patients (131 patients) had a CT or PET/CT to rule out lytic lesions during their outside workup. Only 22 (16%; 95% CI: 11-23%) had a WS or WB MRI performed prior to referral.

Of the SMM patients that had a repeated diagnostic workup at our institution (N=116), 71 completed a WS or WB-MRI. The cohort was composed of 56% male and 44% female patients, with 31% meeting the PETHEMA risk model and 48% meeting the Mayo high-risk model.

MRI identified >1 focal lesion consistent with MM in 9 patients (13%; 95% CI: 6.6–22.6%). In 7 patients (9.9%; 95% CI: 4.6–19.3%), MRI findings were the sole myeloma-defining event prompting reclassification from SMM to active MM. The remaining 2 patients had concurrent findings of ≥60% bone marrow plasma cells, with one also demonstrating lytic lesions on CT. Lesions identified on MRI ranged in size from 0.7 cm to 2.4 cm, with a median size of 0.95 cm. Patients had an average of 3 focal lesions (range 2-4). The presence of focal lesions did not correlate to higher bone marrow plasmacytosis values (3 patients 10-19%, 1 with 20-29%, 1 with 30-39%, 2 with 50-59%, 2 with 60-70%). Before imaging, 7 of the 8 patients met high risk-SMM criteria by IMWG 2020 or PETHEMA risk stratification, while 2 had no high-risk features.

Conclusion This study highlights a potential gap in clinical practice: an underutilization of MRI in the diagnostic work-up of SMM. MRI findings alone led to the reclassification of nearly 10% of patients from SMM to active MM, suggesting that without MRI diagnosis of MM may be missed resulting in delayed treatment and lost opportunities for early intervention. Barriers to routine MRI use may include lack of insurance coverage and clinician hesitancy to initiate treatment based solely on MRI findings, particularly when CRAB features are absent. Nevertheless, MRI's high sensitivity for detecting marrow involvement, focal lesions, and extramedullary disease highlights its crucial role in risk stratification and management, especially in SMM. These findings support broader incorporation of MRI into the routine evaluation of SMM, in accordance with recommendations from both the NCCN and IMWG.