Liquid extramedullary disease in multiple myeloma strongly predicts a poor prognosis and is associated with bortezomib resistance gene upregulation

Patients with multiple myeloma (MM) relapse with extramedullary disease (EMD) exhibits an aggressive disease course and poor prognostic features. Myelomatous effusion (ME) is a rare subtype of EMD. In this retrospective study, we analyzed the baseline characteristics and therapies of 14 EMD patients relapse with ME and 21 EMD patients relapse without ME. Patients with ME relapse demonstrated higher concentrations of serum lactate dehydrogenase, a higher fraction in the International Staging System stage III, and poorer event-free survival (EFS) (9.3 vs. 36.57 months; P = 0.0013) and overall survival (OS) (12.06 vs. 42.64 months; P < 0.001). The multivariate analysis showed that the presence of ME (hazard ratio [HR] 12.57; P = 0.003) and lack of autologous hematopoietic stem cell transplantation therapy (HR 4.382; P = 0.014) were predictive factors for poor OS. Using single-cell RNA sequencing, we discovered several bortezomib resistance genes were highly expressed in extramedullary malignant plasma cells. The presence of ME strongly predicts a poor prognosis in patients with MM relapse with EMD, and bortezomib resistance genes are highly expressed in extramedullary malignant plasma cells.