Tandem autologous hematopoietic stem cell transplantation in multiple myeloma: A historical perspective and current challenges

Multiple myeloma (MM) is a heterogeneous and relapse-prone hematologic malignancy that remains incurable. For newly diagnosed patients aged 70 years or younger, who are eligible for transplantation, autologous hematopoietic stem cell transplantation (auto-HSCT) is the preferred first-line treatment. In patients with high-risk multiple myeloma (HRMM), some studies have demonstrated that tandem auto-HSCT provides notable benefits over single auto-HSCT, particularly in extending progression-free survival (PFS) and overall survival (OS). Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) currently offers the only potential for long-term cure in MM, its application is limited by high transplant-related mortality (TRM) and the risk of graft-versus-host disease (GVHD). In recent years, the emergence of novel therapies, including proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, and chimeric antigen receptor T-cell (CAR-T) therapy, has posed new challenges to the role of tandem auto-HSCT in MM treatment. This review aims to critically examine the efficacy differences between tandem and single auto-HSCT, and sequential allo-HSCT following auto-HSCT. Furthermore, it will rigorously evaluate the role and challenges of tandem auto-HSCT within the evolving therapeutic landscape.