Identifying Appropriate Candidates for Bispecific Antibodies In “Hard-to-Treat” R/R MM

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Patients with hard-to-treat R/R MM present with aggressive disease characteristics, including rapid progression, high tumor burden, and plasma cell leukemia, with doubling times measured in weeks. These patients require immediate disease control, making the 50-day CAR T manufacturing timeline potentially problematic without effective bridging therapy. Bispecific antibodies offer an attractive off-the-shelf treatment option for rapid disease control, with a median time to response of 3 to 4 months across all approved agents (teclistamab, elranatamab, and talquetamab).

Patient selection for bispecific therapy should be considered at the third relapse when planning fourth-line treatment, particularly given current FDA approvals requiring 4 prior lines of therapy. Ideal candidates include patients with rapid progression who may not be suitable CAR T candidates due to performance status, comorbidities, or inability to wait for cell manufacturing. However, certain patients require special consideration, including those with significant central nervous system involvement or bulky extramedullary disease near critical structures, who may benefit from debulking therapy or radiation before bispecific initiation.

Treatment eligibility extends to patients with controlled HIV infection, stable disease on dialysis, and those with secondary malignancies, demonstrating the broad applicability of bispecific antibodies. Key contraindications include active, uncontrolled infections that must be addressed before treatment initiation. The flexibility of bispecific therapy allows the treatment of patients who might not qualify for CAR T therapy, while maintaining the potential for sequential or combination approaches, as demonstrated by successful cases combining bispecific therapy with subsequent CAR T treatment.