Introduction: Extramedullary disease (EMD) refers to the involvement of soft tissues due to hematogenous spread or the presence of a tumor mass adjacent to bones originating from focal skeletal lesions in patients with multiple myeloma (MM). Although EMD is generally associated with poor prognosis, survival outcomes can vary depending on the site and stage of involvement, as well as the response to therapy.
Methods: This retrospective study analyzed the medical records of 419 adult patients with MM treated at a tertiary referral center in Türkiye between 2010 and 2022. Ninety-nine patients with confirmed extramedullary involvement based on pathological and/or radiological findings were included. 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 commonly used imaging modality (76%). Cytogenetic analysis was available for 73 patients, revealing high-risk cytogenetics in 16.4% of cases. 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 the detection of EMD 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 improved OS. Induction regimen groups showed comparable PFS and OS outcomes. The overall survival analysis for patients with high-risk cytogenetic features showed a decrease in survival (OS HR: 1.9, p = 0.259).
Conclusions: EMD is an adverse prognostic factor in MM. Establishing standardized imaging methods and reporting systems is crucial for diagnosing EMD and clarifying the definitions of 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, are associated with inferior outcome. With a median PFS of 79.5 months with ASCT compared to 30.1 months without ASCT, our findings emphasize the importance of ASCT in the management of MM patients with EMD.
