My Treatment Approach Enhancing Treatment for Relapsed/Refractory Multiple Myeloma (RRMM): Converting Evidence to Effective Clinical Care - Episode 2
Sequencing the Available T Cell– Engaging Therapies, and the Role of Bridging/Holding Therapy in RRMM
Panelists discuss how effective sequencing and bridging strategies for T-cell engaging therapies in (relapsed/refractory multiple myeloma (RRMM) rely on using chimeric antigen receptor T-cell therapy (CAR T) first when feasible, while carefully selecting bridging treatments—such as nonoverlapping bispecifics or selinexor regimens—to manage disease without compromising CAR T readiness or long-term immune function.
Physician Summary: Sequencing and Bridging Strategies for T-Cell Engaging Therapies in RRMM
Sequencing CAR T vs Bispecifics
Guidelines from IMWG and ASCO support using CAR T therapy before bispecific antibodies when possible, due to its potential for durable, deep responses. In practice, CAR T is preferred first if patients are eligible and can wait for manufacturing. Bispecifics are used when rapid disease control is needed or CAR T is not feasible.
Bridging vs Holding Therapy
- Bridging therapy: Actively controls disease while awaiting CAR T.
- Holding therapy: Stabilizes disease with minimal immune suppression, used when progression is slower.
Bridging Therapy Options
- Bispecifics (B-cell maturation antigen [BCMA]: teclistamab, elranatamab): Effective but may impair CAR T efficacy targeting the same antigen.
- Bispecifics (GPRC5D: talquetamab): Preferred when bridging to BCMA-directed CAR T to avoid antigen overlap.
- Selinexor-based regimens: Active in refractory disease, synergistic with proteasome inhibitors, and may support CAR T outcomes (BOSTON, STOMP, COSTA analyses).
- Cytotoxic chemo (VD-PACE, DCEP + IMiD): Used for aggressive disease but can impair marrow/T-cell function.
- Radiation (XRT): For localized disease or symptom control.
Key Takeaway: Choose bridging therapy based on disease tempo, prior therapies, and impact on CAR T readiness, prioritizing nonoverlapping targets and immune preservation.
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