Distinct Clinical Outcomes between Paramedullary and Extramedullary Lesions in Newly Diagnosed Multiple Myeloma

Abstract

This retrospective study aimed to compare the clinical features of paramedullary lesions (PLs) and extramedullary lesions (ELs) of plasmacytomas at diagnosis, using positron emission tomography integrated with computed tomography, using glucose labeled with the positron-emitting radionuclide ¹⁸F (¹⁸F-FDG-PET/CT) in newly diagnosed multiple myeloma (NDMM), and to address their prognostic impact. Sixty-four patients with NDMM presenting ELs (n=22) and/or PLs (n=42) were included. Patients with ELs at initial presentation had unfavorable laboratory parameters of calcium and lactate dehydrogenase, a higher percentage of bone marrow plasma cells, and showed a trend toward advanced international staging system (ISS), compared to patients with PLs. Using X-ray imaging, high bone disease (HBD) was observed in 50% and 71% of patients with ELs and PLs, respectively. After a median follow-up of 29.2 months (range, 3.4-76.5 months) in survivors, patients with ELs had a significantly lower overall survival (OS) (p=0.033) than patients with PLs did, whereas the progression-free survival (PFS) did not differ significantly (p=0.818). However, the PFS after 1^st progression was significantly worse in patients with ELs than in those with PLs (p=0.017). In the multivariate analyses, the negative impact of initial ELs on OS (p=0.033) was sustained. Our results demonstrated the different clinical features and outcomes of ELs and PLs in NDMM. Patients with initial ELs showed a shorter PFS after 1^st progression, which translated into poor OS, providing insight into the different biological effect of ELs.

Keywords: 18F-FDG-PET/CT; Multiple myeloma; Plasmacytomas.

Figure 1

Comparison of osteolytic lesions, visualized by X-ray imaging, between patients with ELs and PLs detected by PET/CT.

Figure 2

Kaplan-Meier estimates of outcome after diagnosis and after 1^st progression, according to the presence of ELs vs. PLs at diagnosis. Probabilities of OS (A), PFS (B), and PFS after 1^st progression (C).

Figure 3

Comparison of immune cell populations between patients with newly diagnosed MM without EMPs (control group) and with EMPs (ELs+PLs). Frequencies of M-MDSCs (A), G-MDSCs (B), CD4⁺ T cells (C), and CD8⁺ T cells (D) were compared. Data (right panel) are presented as the mean±SEM, and t-tests were used to compare the continuous variables. SEM, standard error of the mean.