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

Abstract

Background-aim: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Daratumumab; Liquid extramedullary disease; Multiple myeloma; Myelomatous effusion.