Current landscape and future prospects of bispecific antibodies in multiple myeloma

Abstract Multiple myeloma (MM) remains an incurable plasma cell malignancy despite advances with proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. Bispecific antibodies (BsAbs) have emerged as a transformative, off-the-shelf immunotherapeutic strategy that redirects immune effector cells to eliminate malignant plasma cells. The recent FDA approvals of teclistamab, talquetamab, elranatamab and linvoseltamab have reshaped the therapeutic landscape of relapsed/refractory MM (RRMM), achieving overall response rates (ORR) exceeding 60% in heavily pretreated patients. Teclistamab, targeting BCMA, demonstrated an ORR of 63%, while talquetamab, targeting GPRC5D, achieved an ORR of 74%, even in patients previously treated with T-cell redirection therapies. Elranatamab and linvoseltamab further enriched this armamentarium with comparable efficacy and favorable safety profiles. In addition to these milestones, early-phase data from emerging trispecific antibodies, such as ISB 2001, show ORRs as high as 75% and deep responses, including stringent complete responses (sCR) and minimal residual disease (MRD) negativity. This review provides an integrated analysis of BsAbs in MM, encompassing mechanisms of action, clinical development, efficacy, safety profiles, and future directions. We synthesize the latest clinical trial data, explore strategies for overcoming resistance, and discuss ongoing efforts to optimize combination regimens and sequencing. By critically evaluating these advancements, we highlight the evolving role of BsAbs and trispecific antibodies in redefining treatment paradigms, with the ultimate goal of improving patient outcomes and advancing toward a potential cure for multiple myeloma.