Sequencing Strategies and Patient Selection for Bispecific Antibodies in RRMM

EP: 1.Treatment Decision-Making in Multiple Myeloma at First and Subsequent Relapses

EP: 2.Navigating Novel Therapies: ADCs, BsAbs, and CAR T in RRMM

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EP: 3.Sequencing Strategies and Patient Selection for Bispecific Antibodies in RRMM

EP: 4.Real-World Efficacy and Safety Protocols for Bispecific Antibodies

The sequencing of T-cell redirection therapies requires careful consideration of target expression and T-cell fitness, as prior bispecific exposure can lead to T-cell exhaustion that impacts subsequent treatments. Patients who receive BCMA-directed bispecifics first may experience reduced efficacy from subsequent GPRC5D-targeted therapies due to compromised T-cell function rather than target loss. This has important implications for treatment planning, as maintaining T-cell fitness becomes crucial for maximizing the benefit of sequential immunotherapies throughout a patient’s treatment journey.

Most patients are considered appropriate candidates for bispecific therapy, with very few absolute contraindications identified in clinical practice. The primary concerns relate to disease location rather than patient characteristics, particularly for plasmacytomas in critical anatomical sites where treatment-induced inflammation could cause dangerous complications. Extramedullary disease may show lower response rates, but this can potentially be addressed through radiation therapy or combination approaches, and emerging data with combination therapies may overcome these limitations for patients with challenging disease presentations.

Frailty does not appear to predict either progression-free survival or treatment-related mortality with bispecific antibodies, making these therapies accessible to patients who might not tolerate other interventions. The ability to modify dosing, delay treatments, or temporarily discontinue therapy provides crucial flexibility for managing patients with complex medical conditions. This adaptability, combined with the lack of absolute contraindications, positions bispecific antibodies as viable options for the majority of patients with relapsed/refractory myeloma, including those typically excluded from clinical trials due to advanced age, comorbidities, or social factors.