P-448: Impact of Molecular Cytogenetic Abnormalities on the Risk of Disease Progression in Solitary Bone Plasmacytomas

Introduction: The standard treatment for solitary bone plasmacytoma (SBP) with or without minimal marrow involvement is definitive radiation therapy followed by observation. However, most patients with SBP progress to MM. Whether the presence of high-risk (HR) cytogenetic abnormalities by FISH detected in the clonal plasma cells obtained either directly from the SBP tissue or the corresponding bone marrow aspirate performed at the time of diagnosis is associated with a shorter time to progression (TTP) to MM has not been studied to date.

Methods: We evaluated all patients diagnosed with SBP with or without minimal marrow involvement seen at the Mayo Clinic from January 2012 to July 2022. The presence of del(17p), t(14;16), t(4;14), or +1q (gain or amplification) by FISH in clonal plasma cells was defined as HR.
All patients were required to have had a biopsy-proven plasmacytoma arising from a bone, advanced cross-sectional imaging (positron emission tomography (PET)/computed tomography (CT), whole body-CT Skeletal Survey, or whole-body magnetic resonance imaging (WB-MRI)) demonstrating the absence of any additional lytic or FDG avid bone lesions or plasmacytomas, a posterior iliac crest bone marrow biopsy and aspirate containing fewer than 10% clonal plasma cells and no clinical evidence of CRAB symptoms (anemia, elevated creatinine and hypercalcemia) which would fulfill the diagnosis for MM as per the International Myeloma Working Group (IMWG) criteria. We excluded patients with concurrent light chain amyloidosis, POEMS syndrome, 10% or more plasma cells on bone marrow biopsy, and patients who fulfilled the criteria for smoldering or active MM.

Results: A total of 114 patients were included in this cohort, and FISH was available for 55 patients (48.2%), of which 22 were classified as HR (40%). In patients with FISH results available, more patients with HR FISH (N = 20, 91%) progressed to MM compared to patients without HR FISH (N=16,48%) (p=0.0012) after a median follow-up of 54 months. The median TTP to MM for patients with HR FISH was 8 months (95%CI 6.3-26) compared to 42 months (95%CI 25-NR) in patients without HR FISH (p < 0.001). In patients with HR FISH, 59% progressed within 12 months of diagnosis compared to 15% of patients without HR FISH (p < 0.001) and 73% of patients with HR FISH progressed within 24 months of diagnosis compared to 27% of patients without HR FISH (p < 0.001). In a multivariate analysis, only the presence of HR FISH was a significant predictor for shorter TTP to MM, independent of the presence of minimal marrow involvement and an abnormal serum free light chain (sFLC) ratio at diagnosis.

Conclusions: Patients with SBP and HR FISH have a significantly higher risk and shorter TTP to MM compared to patients with SBP and without HR FISH. There is an unmet need to investigate novel therapeutic strategies to prevent the rather rapid disease progression to MM in this patient population.