Background: Zevorcabtagene autoleucel (Zevor-cel, CT053), a fully human autologous anti- B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell

Summary: Multiple myeloma (MM) is a clonal malignancy of plasma cells characterized by frequent relapse and therapeutic resistance. G protein‐coupled receptor class C group 5 member D ( GPRC5D ) has emerged as a promising immunotherapeutic target due to its high and selective expression in MM cells and minimal presence in normal tissues. This review outlines the structural features and expression profile of GPRC5D , emphasizing its relevance to disease biology and prognosis. We highlight recent advances in GPRC5D‐targeted therapies, including antibody–drug conjugates (ADCs), bispecific and trispecific antibodies and chimeric antigen receptor T (CAR T)/natural killer (NK)‐cell therapies, all demonstrating encouraging efficacy in relapsed/refractory MM. Key challenges, such as antigen escape and the need for optimized combination strategies, are also discussed. As GPRC5D‐targeted agents advance through clinical development, large‐scale prospective trials will be essential to define their therapeutic positioning and improve patient outcomes. GPRC5D is poised to become a leading next‐generation target in MM immunotherapy following B‐cell maturation antigen.

Extramedullary involvement (extramedullary disease, EMD) is an aggressive subtype of multiple myeloma (MM) characterized by myeloma subclones proliferating independently of the bone marrow microenvironment, often associated with high-risk cytogenetic abnormalities, immune evasion, and treatment resistance. While significant breakthroughs have been achieved in MM treatment with the sequential approval of proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies, prognosis remains poor once EMD develops. Even in the era of immunotherapy, the survival benefit for EMD patients has not shown significant improvement. This review systematically summarizes therapeutic options for MM patients with EMD, aiming to provide evidence-based guidance for EMD treatment.

Background: Although epirubicin is used among therapeutic options for multiple myeloma (MM), its clinical use remains limited, in part because the subgroup of patients most likely to benefit has not been clearly defined. Identifying robust biomarkers capable of predicting chemosensitivity is therefore essential to aimed personalized treatment strategies and enhance therapeutic outcomes. This study sought to characterize the molecular effects of epirubicin in MM cells, elucidate its tumor-suppressive mechanisms, and determine potential indicators for patient stratification. Materials and Methods: The half-maximal inhibitory concentration (IC50) for epirubicin was quantified using the Cell Counting Kit-8 (CCK-8) viability assay. Gene expression alterations before and after epirubicin exposure were investigated via microarray profiling, followed by bioinformatic interrogation of publicly available datasets to examine the prognostic value of CDC20 expression in MM. Subsequently, functional validation was performed through in vitro assays and in vivo xenograft models to evaluate the impact of epirubicin on cell-cycle progression and tumor growth. Results: Epirubicin exhibited an IC50 of 23.85 μM in MM.1R cells. Transcriptome analysis revealed 115 genes upregulated and 25 genes downregulated post-treatment. Among the significantly altered genes were CDC20 (log FC = –2.409), KIF20A (log FC = –1.693), FAM72A (log FC = –1.742), CCNB1 (log FC = –1.787), PIF1 (log FC = –2.201), and LMNB1 (log FC = –1.589). Higher CDC20 expression was associated with shorter overall survival (OS), event-free survival (EFS), and post-progression survival (PPS). Mechanistic studies demonstrated that epirubicin triggers G2/M arrest in MM cells by suppressing CDC20, and in vivo experiments corroborated that decreased CDC20 expression contributes to reduced tumor proliferation via cell-cycle blockade. Conclusion: Epirubicin exerts anti-myeloma effects by downregulating CDC20 and inducing cell-cycle arrest in MM, highlighting CDC20 as a potential biomarker for identifying MM patients likely to benefit from epirubicin.

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.