Identification of patients at high risk of secondary extramedullary multiple myeloma development

Abstract

Multiple myeloma (MM) is characterized by malignant plasma cell infiltration of the bone marrow. In extramedullary multiple myeloma (EMD), a subclone of these cells migrates out of the bone marrow. Out of 4 985 MM patients diagnosed between 2005 and 2017 in the Czech Republic, we analyzed 234 secondary EMD patients to clarify risk factors of secondary EMD development. We found younger age [<65 years; odds ratio (OR) 4Á38, 95% confidence interval (CI): 2Á46-7Á80, P < 0Á0001], high lactate dehydrogenase (LDH) levels (>5 lkat/l; OR 2Á07, 95% CI: 1Á51-2Á84, P < 0Á0001), extensive osteolytic activity (OR 2Á21, 95% CI: 1Á54-3Á15, P < 0Á001), and immunoglobulin A (IgA; OR 1Á53, 95% CI: 1Á11-2Á11, P = 0Á009) or the non-secretory type of MM (OR 2Á83; 95% CI: 1Á32-6Á04, P = 0Á007) at the time of MM diagnosis to be the main risk factors for secondary EMD development. Newly diagnosed MM (NDMM) patients with subsequent EMD had inferior median progression-free (PFS) and overall (OS) survival when compared to NDMM patients without future EMD [mPFS: 13Á8 months (95% CI: 11Á4-16Á3) vs 18Á8 months (95% CI: 17Á7-19Á9), P = 0Á006; mOS: 26Á7 months (95% CI: 18Á1-35Á4) vs 58Á7 months (95% CI: 54Á8-62Á6), P < 0Á001]. We found that NDMM patients with specific risk factors associated with secondary EMD development have a more aggressive disease course before secondary EMD develops.

Unexpected Heterogeneity of Newly Diagnosed Multiple Myeloma Patients with Plasmacytomas

“…Moreover, this heterogeneity is strongly reflected in patients’ prognosis. It is obvious that the clinical course of NDMM patients with plasmacytomas and RRMM patients with plasmacytomas is dramatically different [ 12 , 14 , 18 , 19 ].…”

“…In accord with recent papers [ 7 , 8 , 33 ], our clinical and research groups have long considered PS and EMD plasmacytomas as very different entities in both NDMM and RRMM patients. Thus, we have studied them separately [ 9 , 12 , 18 , 34 ]. However, other groups describe all plasmacytomas outside of BM environment as one unit often making comparisons impossible [ 13 , 28 , 35 ].…”

“…Although the appearance of plasmacytomas is generally associated with impaired prognosis, there are some treatment results of NDMM with plasmacytomas that are comparable to those of NDMM patients with strictly intra-medullar disease [ 14 , 19 , 20 ]. However, as we have previously described, development of plasmacytomas in RRMM patients is associated with extremely poor prognosis [ 12 , 18 ]. We believe that aggressivity of plasmacytomas in RRMM patients is likely due to disease-related factors.…”

“…These plasmacytomas can be found in both newly diagnosed MM (NDMM) patients (2.4–11.5% of cases) [ 14 , 15 , 16 ] and in relapsed/refractory MM (RRMM) patients (3.4–27.4% of cases) [ 12 , 16 , 17 , 18 ]. The range of plasmacytoma incidence is predominantly caused by the different sensitivities of the imaging methods used [ 12 , 13 , 14 , 15 , 16 , 17 , 18 ], while historical methods, such as skeletal survey, have only a limited sensitivity for detection of PS or EMD plasmacytomas [ 7 , 8 , 9 ].…”

“…We have previously described NDMM patients with early progression with plasmacytomas. These patients had an aggressive disease course from the disease onset, together with gain (1q21) [ 18 ].…”