How are BCMA-directed bispecific antibodies currently utilized in real-world practice for MM?

The Multiple Myeloma Hub was pleased to speak with Hang Quach, St Vincent’s Hospital Melbourne and University of Melbourne, Melbourne, AU. We asked, How are B-cell maturation antigen (BCMA)-directed bispecific antibodies currently utilized in real-world practice for multiple myeloma (MM)?

In this interview, Professor Quach discussed how the development and integration of BCMA-directed bispecific antibodies have transformed the treatment landscape for relapsed/refractory multiple myeloma (RRMM). Quach covered regulatory approvals, key clinical trial data, strategies for managing toxicities and infections, considerations for community-based treatment, and the adoption of flexible dosing approaches in real-world clinical practice.

Key learnings

• Elranatamab and teclistamab are currently the only BCMA-directed bispecific antibodies that are approved for the treatment of relapsed/refractory multiple myeloma (RRMM).

• Elranatamab received approval based on data from the pivotal phase II MagnetisMM-3  (NCT04649359) study, which, at a median follow-up of 28.4 months, demonstrated an overall response rate (ORR) of 61% and a median progression-free survival (PFS) of 17.2 months in patients with heavily pretreated RRMM.¹

• Teclistamab received approval based on data from the phase I/II MajesTEC-1 (NCT04557098) study in patients with heavily pretreated RRMM, which, at a median follow-up of 14.1 months, demonstrated an ORR of 63% and a median PFS of 11.3 months.²

• Both elranatamab and teclistamab carry a risk of cytokine release syndrome (CRS), hematologic toxicity, and infections. CRS is typically low-grade, and most commonly occurs during initial doses.^1,2

• In clinical practice, early or prophylactic use of tocilizumab is increasingly being adopted to mitigate the risk of CRS without negatively impacting response to BCMA-directed bispecific antibody treatment. In one study, a single prophylactic dose of tocilizumab reduced the incidence of CRS from 73% to 26% when given alongside teclistamab.³

• Some centers use corticosteroids such as dexamethasone to treat Grade 1 CRS, although evidence supporting this approach is limited compared with that of tocilizumab.⁴

• Outpatient administration of teclistamab and elranatamab is becoming more common; however, inpatient monitoring remains the standard of care in many institutions.

• Comprehensive infection prevention and monitoring protocols are vital to manage opportunistic infections that are commonly observed with BCMA-directed bispecific antibody therapy. 

• Intravenous immunoglobulin replacement therapy is often initiated in response to hypogammaglobulinemia, particularly when IgG levels fall below 400 mg/dL or if the patient experiences recurrent infections.⁵

• There is a growing shift in real-world practice toward flexible dosing schedules for BCMA-directed bispecific antibodies, with many clinicians transitioning to biweekly dosing earlier than in trial protocols.

• Monthly dosing and fixed-duration treatment strategies are currently under investigation and may further optimize treatment outcomes in the future.

• Overall, BCMA-directed bispecific antibodies represent a significant advancement in the treatment of RRMM; however, their effective use requires proactive toxicity management and ongoing refinement of real-world practices.

This educational resource is independently supported by Pfizer. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence on the content of this resource.