Overview of BCMA-directed therapies for multiple myeloma

On March 5, 2026, the Multiple Myeloma Hub held a virtual symposium, titled Optimizing dosing of BCMA-directed therapies for improved quality of life in multiple myeloma. During the symposium, Fredrik Schjesvold, Oslo University Hospital, Oslo, NO, provided an overview of B-cell maturation antigen (BCMA)-directed therapies in multiple myeloma (MM). 

During this presentation, Schjesvold provides an overview of currently available BCMA-directed treatment modalities, including antibody–drug conjugates (ADCs), bispecific antibodies, and chimeric antigen receptor (CAR) T-cell therapies. Schjesvold outlines differences in mechanisms of action (Figure 1), regulatory approvals, treatment settings, and key efficacy and safety data across approved agents (Figures 2 and 3).  

Key points 

• BCMA-directed treatment modalities for MM, include ADCs, bispecific antibodies, and CAR T-cell therapies.¹ 
• All BCMA-directed therapies target BCMA on myeloma cells, but they differ in their mechanisms of action for inducing tumor cell death. 
• ADCs deliver a cytotoxic payload to BCMA-expressing cells following internalization and do not directly activate T cells.¹ 
• Ocular toxicity is an adverse effect associated with belantamab mafodotin, an ADC, and is generally reversible with dose modification or treatment interruption.^2,3 
• Bispecific antibodies simultaneously target BCMA on myeloma cells and CD3 on T cells, leading to T-cell activation and tumor cell killing.¹ 
• Cytokine release syndrome (CRS) is commonly observed with bispecific antibodies, particularly early in treatment, and may be mitigated with step-up dosing and supportive care.^5-7 
• Infections are frequently observed with bispecific antibodies and may require prophylactic strategies, including immunoglobulin replacement and antimicrobial prophylaxis.¹³ 
• CAR T-cell therapies involve ex vivo modification of patient-derived T cells to target BCMA, followed by reinfusion as a single treatment.¹ 
• CAR T-cell therapies are associated with CRS and neurotoxicity, with onset typically occurring early following infusion.^8-10 
• Treatment administration differs across modalities; ADCs and bispecific antibodies require repeated dosing, while CAR T-cell therapies are administered as a single infusion. 
• Response rates and progression-free survival vary across treatment modalities and disease settings, with higher response rates generally observed in earlier lines of therapy. 
• Infection risk differs between modalities, with prolonged risk observed with bispecific antibodies and a more time-limited risk observed following CAR T-cell therapy.¹³ 
• Each BCMA-directed therapy class has a distinct safety profile, including ocular toxicity associated with belantamab mafodotin, and immune-mediated toxicities, which are more commonly observed with bispecific antibodies and CAR T-cell therapies. 
• Selection of BCMA-directed therapy requires consideration of efficacy, safety, treatment burden, and patient-specific factors. 

This independent educational activity was supported by GSK. All content was developed independently by SES in collaboration with the faculty. The funder was allowed no influence on the content of this activity.