ASCO 2024: BCMA-Directed Therapies in Relapsed Multiple Myeloma

Myeloma specialist Dr. Matthew J. Rees, MD, from Mayo Clinic, and colleagues shared their findings at the ASCO 2024 conference in June.

The study revealed that BCMA-directed CAR T cell therapy significantly improves survival outcomes in relapsed myeloma patients compared to antibody-drug conjugates and bispecific antibodies, making it a promising option for patients with limited treatment choices.

Comparing BCMA-Targeted Therapies: CAR T Cells, ADCs, and Bispecific Antibodies

BCMA (B-cell maturation antigen) is a protein commonly found on myeloma cells, making it a valuable target for therapies. The study focused on three types of BCMA-targeted treatments:

• CAR-T Cells: (Chimeric Antigen Receptor) A type of immunotherapy where a patient's T cells are genetically modified to target and kill myeloma cells.
• Antibody-Drug Conjugates (ADCs): These are antibodies linked to cancer-killing drugs that specifically target BCMA on myeloma cells, delivering the drug directly to the cancer.
• Bispecific antibodies, also called T-Cell Engagers (TCEs), bring T cells into close proximity to myeloma cells, enhancing the immune system's ability to destroy the cancer cell.

Each of these therapies represents a new approach to treating myeloma. This study used data available from investigational and commercial medicines.

Study Findings: Efficacy and Safety of BCMA-Directed Therapies

The study included 385 patients treated at Mayo Clinic from April 2018 to June 2023  with BCMA-targeted therapies. The most relevant findings are: 

• Overall Response Rate: The percentage of patients whose myeloma was reduced after treatment was higher with CAR-T, with 86% of patients achieving a response.
• Progression-Free Survival: Time after treatment when myeloma is controlled. Patients treated with CAR T showed the longest remissions. 
• Overall Survival: Life expectancy after treatment. CAR T therapy significantly improved overall survival compared to other BCMA-directed treatments. 

What Do These Findings Represent for High-Risk Myeloma Patients? 

Multiple treatment options are being tested in relapsed and refractory myeloma patients; these are subgroups of high-risk myeloma features with fewer effective options. 

Despite the promising results for CAR-T and bispecific antibodies, patients previously treated with BCMA therapy showed poor outcomes regardless of the treatment used. The median progression-free survival was particularly low for these patients, highlighting the need for further research and the development of more effective treatments.

This study highlights the survival benefits of BCMA-directed CAR T therapy in relapsed myeloma patients. However, high-risk groups remain challenging to treat, indicating a need for ongoing research and new treatment strategies. These findings are a significant step forward in improving outcomes for myeloma patients, and further studies will help refine these therapies for broader application.

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Source: 

• Class comparison of BCMA-directed therapies in relapsed multiple myeloma.