Population-Level Outcomes in Solitary Plasmacytoma: A Surveillance, Epidemiology, and End Results (SEER) Study

Introduction Solitary plasmacytoma (SP) is a plasma cell dyscrasia characterized by a single tumor consisting of clonal plasma cells. Typical management involves local therapy, usually with a definitive course of radiation therapy (RT), less often surgical excision. Although local therapy, including RT, is administered with curative intent, patients with SP have high risk of progression to multiple myeloma (MM). Comparative outcome data describing the natural history of patients treated for SP derive from older retrospective studies. The impacts of prior SP therapy on survival in patients who transform to MM, and the impact of transformation to MM on survival of patients with SP, are not well-characterized. We conducted a population-level study comprehensively examining the outcomes of patients diagnosed with SP in the Surveillance, Epidemiology, and End Results (SEER) database. Methods We identified patients with histologically confirmed diagnosis of SP in the SEER database between 2000 and 2020. Only patients with complete survival (including classification of death as attributable to cancer diagnosis or other causes) as well as treatment data were included. Patients diagnosed with SP who were recorded to have histopathological evidence of subsequently developing multiple myeloma (MM) after SP diagnosis were classified as having transformed; patients who transformed from SP to MM in under 4 months were excluded, as such patients may have initially been misclassified as having SP. Competing risk methods were used to estimate MM transformation cumulative incidence rates. Survival analyses investigating the role of frontline SP management (observation versus treatment, defined as any of systemic therapy, radiation, or surgery), transformation status (yes versus no) and other demographic variables in the entire SP cohort were conducted. Overall survival and cancer-specific survival were evaluated using a multivariable Cox and Fine-Gray competing risk regression models, respectively. To assess survival differences between de novo and transformed MM, we assembled a cohort of patients with MM and no prior SP history, matched by age, sex and year of diagnosis, to the transformed MM cohort, and compared survival in the two cohorts using a Cox regression model. Analyses were conducted using R version 34.3.1. Results A total of 4319 patients with SP were identified. A majority (n=2335, 54.1%) were older than age 60 at diagnosis, were male (n=2669, 61.8%), and had bony (n=3157, 75.9%) rather than extramedullary SPs. Most (n=3125, 72.4%) patients were treated with radiation therapy as frontline management; 536 patients (12.4%) were managed with observation. In total, 414 (9.6%) patients developed progression to multiple myeloma. Annual incidence of transformation to MM was highest in the first year after diagnosis (28 transformations per 1000 person-years), with declining incidence of progression over time. Only age older than 60 (HR 1.36, 95%CI 1.12-1.66) was associated with increased risk of SP transformation to MM across the entire SP and bone and extramedullary SP cohorts. Factors associated with reduced overall survival included age of 60 or greater (HR 3.18, 95% CI 2.88-3.52), bony rather than extramedullary plasmacytoma (HR 1.30, 95% CI 1.16 - 1.43) and progression to MM (HR 1.39, 95% CI 1.19-1.64). Compared to observation, both surgery (HR 0.50, 95%CI 0.40-0.61) and RT (HR 0.54 ,95%CI 0.48-0.62) were associated with improved survival. Similar associations were observed between these factors and cancer-specific survival. Age of 60 or greater (HR 2.29, 95% CI 2.04-2.57), bony rather than extramedullary plasmacytoma (HR 1.72, 95% CI 1.50 - 2.00) and progression to MM (HR 1.31, 95% CI 1.09-1.58) were associated with reduced cancer-specific survival. Compared to observation, both surgery (HR 0.61, 95%CI 0.46-0.79) and RT (HR 0.65, 95%CI 0.55-0.77) were associated with improved survival. Compared to patients with de novo MM, patients with SP transformed to MM experienced improved overall survival (HR 1.19, 95% CI 1.04-1.5). Conclusions Although frontline therapy for SP was not associated with reduced risk of transformation to MM, receipt of frontline therapy was associated with improved overall survival and cancer-specific survival in the SEER cohort. This underscores the critical importance of definitive therapy for patients diagnosed with SP.