Bispecific antibodies in multiple myeloma: maximizing potential through rational combination therapies

Bispecific antibodies have emerged as a transformative immunotherapeutic strategy in multiple myeloma (MM). Early constructs such as BiTEs paved the way for full-length IgG-based antibodies with improved pharmacokinetics and safety profiles. As of 2025, teclistamab, elranatamab, linvoseltamab (all BCMA×CD3) and talquetamab (GPRC5D × CD3) have received regulatory approval for relapsed/refractory MM. Investigational agents targeting FcRH5 (cevostamab) and next-generation constructs with altered binding configurations targeting BCMA are under clinical evaluation. Despite high response rates in late-line therapy, resistance via antigen loss, T-cell dysfunction and soluble BCMA presents a major challenge. Combinations with IMiDs, checkpoint inhibitors and dual-targeting approaches are being tested to enhance durability. Frontline studies currently investigate if bispecific antibodies can further deepen responses and induce MRD negativity when used as part of induction therapy. As clinical data matures, bispecific antibodies are likely to redefine MM treatment, by offering an off-the-shelf, scalable alternative to CAR-T therapy with curative potential in selected patient populations.