Year: 2026
Type: article
Abstract: Bispecific antibodies have reshaped the therapeutic landscape for relapsed/refractory multiple myeloma (RRMM), complementing proteasome inhibitors, IMiDs, and anti-CD38 antibodies and competing with BCMA-directed CAR-T cells. In this review, we discuss the structure, mechanisms of action, and clinical data for currently approved and emerging T-cell redirecting antibodies and discuss practical questions around sequencing with CAR-T therapy, toxicity mitigation, and resistance. Bispecific T-cell engagers have shown high response rates in early relapse, as well as multidrug-refractory disease and post-CAR-T relapse, but are limited by continuous dosing, infections, hypogammaglobulinemia, cytopenias, cytokine release syndrome (CRS), and neurologic toxicity. We review emerging concepts in resistance like T-cell exhaustion, antigen loss, soluble BCMA, and extramedullary disease and discuss strategies to enhance efficacy, including combinations with anti-CD38 antibodies and IMiDs. Bispecific antibodies have become indispensable in relapsed myeloma, and for patients who are ineligible for or relapse after CAR-T therapy. With multiple clinical trials and new molecules in development, rational sequencing and combination approaches will determine how far their promise translates into durable disease control.
Source: European Journal Of Haematology
DOI: 10.1111/ejh.70301
Authors: Mahin Bhatt, S. Vincent Rajkumar, Shaji Kumar
Institution: Mayo Clinic
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funder: National Institutes of Health
Awards: G9000011126, G9000167924
OpenAlex ID: W7204156306