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Opinion|Videos|May 16, 2025

Discussing the Treatment Options for RRMM Following Progression After BCMA CAR T Therapy

Author(s)Aimaz Afrough, MD, Natalia Neparidze, MD

Panelists discuss how various treatment options, including selinexor-based regimens, B-cell maturation antigen (BCMA)–targeted therapies, bispecific antibodies, and CELMoDs, can be used to manage relapsed/refractory multiple myeloma following progression on BCMA-directed chimeric antigen receptor T-cell therapy (CAR T).

Episodes in this series

EP. 1 Exploring the Treatment Options for RRMM

EP. 1 Exploring the Treatment Options for RRMM

EP. 2 Sequencing the Available T Cell– Engaging Therapies, and the Role of Bridging/Holding Therapy in RRMM

EP. 2 Sequencing the Available T Cell– Engaging Therapies, and the Role of Bridging/Holding Therapy in RRMM

EP. 3 Exploring T-Cell Fitness Strategies to Optimize Clinical Outcomes in RRMM

EP. 3 Exploring T-Cell Fitness Strategies to Optimize Clinical Outcomes in RRMM

EP. 4 Discussing the Treatment Options for RRMM Following Progression After BCMA CAR T Therapy

EP. 4 Discussing the Treatment Options for RRMM Following Progression After BCMA CAR T Therapy

EP. 5 Important Patient and Clinical Considerations When Choosing Therapy in RRMM Following CAR T Therapy

EP. 5 Important Patient and Clinical Considerations When Choosing Therapy in RRMM Following CAR T Therapy

EP. 6 Highlighting Selinexor in the RRMM Setting After CAR T Therapy

EP. 6 Highlighting Selinexor in the RRMM Setting After CAR T Therapy

EP. 7 Bispecific Antibodies for the Treatment of RRMM in the Post CAR T Setting

EP. 7 Bispecific Antibodies for the Treatment of RRMM in the Post CAR T Setting

EP. 8 Practical Recommendations for Community Oncologists Treating RRMM

EP. 8 Practical Recommendations for Community Oncologists Treating RRMM

Physician Summary: Treatment Options After Progression Following BCMA-Directed CAR T Therapy

After progression on BCMA-directed CAR T therapy, several treatment options have demonstrated efficacy in relapsed/refractory myeloma:

Selinexor-based regimens: Effective in CAR T–refractory myeloma (BOSTON trial data). Selinexor can help control disease and may enhance subsequent CAR T efficacy.
BCMA-targeted therapies:
Teclistamab, elranatamab, and belantamab mafodotin (immune-engager therapies) have shown promise as next-line therapies following BCMA-directed CAR T relapse.
Talquetamab: A GPRC5D-targeted bispecific antibody that has shown potential in patients with relapsed BCMA-directed CAR T therapy.
Cytotoxic chemotherapy: Can be considered for aggressive disease or as a bridge while awaiting other treatments but carries the risk of T-cell suppression.
CELMoDs: Novel immunomodulatory drugs (IMiDs) may enhance CAR T functionality and could offer benefit in post-CAR T relapse settings.

Key Takeaway: Post-BCMA CAR T progression requires careful consideration of available therapies like bispecific antibodies, selinexor, and novel CELMoDs to manage disease and potentially enhance response to future treatments.

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