Publication details
High-risk genomic features predict extramedullary progression in multiple myeloma with paraskeletal plasmacytomas
| Authors | |
|---|---|
| Year of publication | 2026 |
| Type | Peer-reviewed scientific article |
| Magazine / Source | HemaSphere |
| MU Faculty or unit | |
| Citation | |
| web | https://onlinelibrary.wiley.com/doi/10.1002/hem3.70395 |
| Doi | https://doi.org/10.1002/hem3.70395 |
| Keywords | multiple myeloma; next generation sequencing |
| Description | Multiple myeloma (MM) may present with extraosseous manifestations, including paraskeletal (PS) plasmacytomas extending from osteolytic bone lesions and true extramedullary disease (EMD) arising independently of the bone microenvironment, which represent clinically and biologically distinct entities. While EMD is consistently associated with poor prognosis, PS plasmacytomas are observed in approximately 30% of newly diagnosed MM (NDMM) patients and are generally associated with outcomes comparable to those without extramedullary involvement.1, 2 However, growing evidence suggests that a subset of PS lesions may carry an increased risk of progression to secondary EMD, a condition linked to treatment resistance and dismal outcomes.3 In the era of genomic risk stratification as recommended by the International Myeloma Society/International Myeloma Working Group (IMS/IMWG),4 it remains unclear whether genomic features can identify PS patients at risk of subsequent extramedullary progression. To address this, we analyzed patients with newly diagnosed and relapsed MM treated at University Hospital Brno between 2015 and 2025. A total of 888 NDMM patients with defined extramedullary status based on advanced imaging were included. Genomic and cytogenetic analyses were performed on CD138+ bone marrow plasma cells (BMPCs) and native plasmacytoma tissue samples (PS or EMD). Genomic profiling was performed using in-house targeted next-generation sequencing (NGS)5 and fluorescence in situ hybridization to assess recurrent genetic alterations. Detailed methodology is provided in the Supporting Information S1: Supplementary Methods. The study was approved by the institutional ethics committee, and all patients provided informed consent. Within this cohort, patients were stratified as follows: 646 without extraosseous manifestation, 226 with PS plasmacytomas, and 16 with primary EMD. Clinical characteristics and outcomes were consistent with previous reports (Supporting Information S2: Supplementary Materials).3 Among patients without baseline EMD (n = 872), the presence of PS plasmacytomas at diagnosis was associated with an increased risk of subsequent EMD development. Secondary EMD developed in 8.0% (18/226) of patients with PS lesions compared to 3.7% (24/646) of patients without baseline PS involvement (odds ratio [OR] 2.24; 95% CI 1.19–4.22; P = 0.017). Furthermore, EMD emerged earlier in patients with baseline PS (median 22.3 vs. 38.0 months, P = 0.017), supporting the hypothesis that a subset of PS lesions is associated with increased risk of extramedullary progression. Multiple myeloma (MM) may present with extraosseous manifestations, including paraskeletal (PS) plasmacytomas extending from osteolytic bone lesions and true extramedullary disease (EMD) arising independently of the bone microenvironment, which represent clinically and biologically distinct entities. While EMD is consistently associated with poor prognosis, PS plasmacytomas are observed in approximately 30% of newly diagnosed MM (NDMM) patients and are generally associated with outcomes comparable to those without extramedullary involvement. However, growing evidence suggests that a subset of PS lesions may carry an increased risk of progression to secondary EMD, a condition linked to treatment resistance and dismal outcomes. |
| Related projects: |