bortezomib; carfilzomib; cytogenetics; disease; extramedullary disease; lenalidomide; melflufen plus dexamethasone; multiple myeloma; open-label; p53 deletion; pomalidomide; prognostic factors; therapy

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) 4 center dot 38, 95% confidence interval (CI): 2 center dot 46-7 center dot 80, P < 0 center dot 0001], high lactate dehydrogenase (LDH) levels (>5 mu kat/l; OR 2 center dot 07, 95% CI: 1 center dot 51-2 center dot 84, P < 0 center dot 0001), extensive osteolytic activity (OR 2 center dot 21, 95% CI: 1 center dot 54-3 center dot 15, P < 0 center dot 001), and immunoglobulin A (IgA; OR 1 center dot 53, 95% CI: 1 center dot 11-2 center dot 11, P = 0 center dot 009) or the non-secretory type of MM (OR 2 center dot 83; 95% CI: 1 center dot 32-6 center dot 04, P = 0 center dot 007) 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: 13 center dot 8 months (95% CI: 11 center dot 4-16 center dot 3) vs 18 center dot 8 months (95% CI: 17 center dot 7-19 center dot 9), P = 0 center dot 006; mOS: 26 center dot 7 months (95% CI: 18 center dot 1-35 center dot 4) vs 58 center dot 7 months (95% CI: 54 center dot 8-62 center dot 6), P < 0 center dot 001]. We found that NDMM patients with specific risk factors associated with secondary EMD development have a more aggressive disease course before secondary EMD develops.