P966: smoldering multiple myeloma (mm) progressing to active mm during follow-up: reduced bone disease and improved progression-free and overall survival compared to de-novo newly diagnosed mm

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Analyses of consecutive serum samples suggests that active multiple myeloma (MM) typically arises from precursor conditions including monoclonal gammopathy and smoldering MM (SMM), yet, only a minority of patients (pts) are diagnosed during their precursor stage. Patients diagnosed with SMM are routinely followed and screened for progression to active disease, supposing such surveillance will identify myeloma defining events (MDE) early and consequently hasten treatment, prevent morbid complications and improve outcomes. To what extent this approach is successful is not well established. Aims: We aimed to investigate the clinical phenotype and outcomes of SMM pts who progress to active newly diagnosed MM, while under routine hematology clinic surveillance (postSMM), in comparison to a matched cohort of pts who present as “de-novo” newly diagnosed MM (dnNDMM). Methods: In this cross sectional single center retrospective cohort study we screened medical record data-base in our institution to identify all SMM pts who progressed to active MM between 01/2012 and 02/2023. For each pt in this cohort, we randomly selected a pt who presented as dnNDMM, matched by age and calendar year of active disease diagnosis. SMM, active MM and response to treatment were defined by IMWG criteria. Demographic and disease characteristics, first line treatment, progression free survival (PFS) and overall survival (OS) were compared. Bone disease with either 3 and above lytic lesions, a pathological fracture or hypercalcemia was considered detrimental. Bone lesions and renal failure were classified as potentially irreversible MDEs. Results: 39 SMM pts who progressed to active MM during median clinic follow-up of 26 months (mo) (range 3-167) were identified and matched with 39 dnNDMM pts. There were no statistically significant differences in demographics, disease characteristics and first line treatment and response rates between groups, excluding female predominance in the SMM group and higher plasma cells (PC) infiltration in the dnNDMM. Potentially irreversible MDEs were more frequent in dnNDMM compared with postSMM, 77% vs 56% (p=0.055), including renal failure 23% vs 15.7% (p=0.055), hypercalcemia 13% vs 0% (p<0.001) and lytic lesion 64% vs 44% (p=0.055). Pts with dnNDMM had higher rate of bone pain, 59% vs 28% (p=0.006), pathological fractures 31% vs 5% (p=0.003), and detrimental bone disease 51% vs 15% (p=0.001). Upfront treatment included bortezomib in 95% vs 67%, (p=0.002) in dnNDMM vs postSMM, respectively, other medication were at comparable rates. Median follow-up from time of active MM was 28 months (range: 1-164). Median PFS and OS were significantly longer in the postSMM group vs dnNDMM cohorts: PFS 40 vs 21mo, p=0.042, OS not reached vs 62 mo (p=0.011). (Figure 1). Summary/Conclusion: SMM pts progressing to active MM while under clinic surveillance had less frequent bone disease, and in particular less detrimental bone disease, and were less likely to present with renal failure compared to dnNDMM pts, nevertheless over half still developed potentially irreversible MDEs when progressing to active MM. postSMM pts had significantly better PFS and OS compared to dnNDMM. This may reflect early detection of progression and treatment initiation; another possible explanation is that pts with more indolent MM biology may have longer periods of precursor condition, hence increasing their likelihood to be diagnosed by incidental laboratory tests.Keywords: Smoldering, Multiple myeloma