Advances in multiple myeloma: key updates from the ASH 2025 meeting.

Abstract

The therapeutic landscape of multiple myeloma (MM) is undergoing rapid transformation with the expansion of immune-based strategies. This editorial summarizes key MM abstracts presented at the American Society of Hematology (ASH) 2025 meeting, highlighting how bispecific antibodies (BsAbs), minimal residual disease (MRD)-adaptive approaches, and next-generation immune platforms are reshaping treatment across all MM disease stages. In newly diagnosed MM (NDMM), minimal residual disease (MRD)-adaptive consolidation with linvoseltamab in IMMUNOPLANT converted persistent MRD positivity to MRD negativity in all evaluable patients, supporting biologically guided treatment intensification. In transplant-ineligible (TIE) NDMM patients, TecLille showed that antibody-only therapy achieved deep responses with manageable infection risks. In early relapsed/refractory MM (RRMM), the pioneering phase III MajesTEC-3 trial demonstrated significant progression-free survival (PFS) and overall survival (OS) benefits with BsAb teclistamab plus daratumumab compared to other standard triplets, with response rates approaching those historically observed with chimeric antigen receptor (CAR) T cell therapy. A novel rational BsAb combination of BsAb elranatamab anda cereblon E3 ligase modulatory drug (CELMoD) iberdomide in MagnetisMM-30 showed promising synergy despite cytopenias and updates to combination BsAb targeting in RedirecTT-1 demonstrated major activity in difficult to treat extramedullary myeloma (EMM). First-in-human inMMyCAR data showcased the forefront of engineered immune strategies, by introducing an in vivo CAR-T product as a proof-of-concept platform, with tremendous potential to streamline the access to therapy. Collectively, these studies signal a shift toward earlier and adaptive immunotherapy in all phases of MM disease, while underscoring the importance of infection mitigation and long-term safety evaluation.