Clinical factors determining the survival of multiple myeloma patients with extramedullary disease: a single-center experience

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Extramedullary disease (EMD) is defined as a soft tissue involvement resulting from hematogenous spread or a tumor mass adjacent to bones arising from focal skeletal lesions in patients with multiple myeloma (MM). Although the survival of EMD is considered to be poor, it may vary depending on the site, and stage of involvement, as well as the response to therapy. Aims: There are few studies in the literature which evaluate the factors affecting survival in patients with EMD. The aims of this study were to determine the demographic and clinical characteristics of EMD among myeloma patients at initial diagnosis or during relapse and to determine the factors affecting the treatment response, overall survival and progression-free survival. Methods: This study retrospectively reviewed the medical records of 419 adult patients with MM who were treated at a tertiary referral center in Türkiye between 2010 and 2022. Ninety-nine patients with MM who had a pathological and/or radiological diagnosis of extramedullary involvement were included in the study. Data were collected from hospital records and the management information system. The average follow-up time was found to be 40±31.5 months. Results: Twenty-seven percent of MM patients were found to have EMD. Extramedullary-extraosseous involvement (EM-E) was observed in 27 (27%) patients. Paraosseous involvement (EM-B) was seen in 72 (72%) patients. PET/CT was the most common imaging modality that was used (76%). Cytogenetic analysis was available in 73 patients and high-risk cytogenetics were found in 16.4% of these patients. Most commonly used induction regimen was bortezomib-cyclophosphamide-dexamethasone (VCD) regimen (36%). Median overall survival (OS) and progression-free survival (PFS) of the patients with EMD were 77 months (range: 58 - 95) and 49 months (range: 39 - 58), respectively. In the univariate analysis; advanced ISS staging (OS HR: 2.42, p = 0.024), high levels of serum Beta-2-Microglobulin (OS HR: 2.46, p = 0.020), and light chain disease (OS median survival 24 months/ 78 months, p = 0.049) were associated with a worse OS. Secondary EMD, defined as EMD detected during MM follow-up, was associated with a worse PFS (HR: 2.87, p = 0.013). In the multivariate analysis; ASCT (OS HR: 0.26, p = 0.001) and low serum creatinine (OS HR: 1.21 p = 0.025) were independently associated with better OS. The PFS and OS outcomes among the induction regimen groups were comparable. The overall survival analysis for patients with high-risk cytogenetic features showed a decrease in survival (OS HR: 1.9, p = 0.259). Summary/Conclusion: EMD is a bad prognostic factor in MM. To diagnose EMD, it is necessary to establish standards for imaging methods and reporting systems to clarify the definition of EMD, EM-E, and EM-B. It is also important to conduct studies on biochemical and cytogenetic markers to identify patients at high risk for EMD, determine appropriate follow-up parameters and reach a consensus on treatment. Our study showed that various clinicals factors including ISS staging, levels of serum Beta-2-Microglobulin and creatinine and EMD subtypes were associated with inferior outcome. In our study, the median PFS for EMD was 79.5 months with ASCT, as opposed to 30.1 months without ASCT, emphasizing the importance of ASCT in the management of MM patients with EMD. Keywords: Risk factor, Multiple myeloma, Myeloma, Survival