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bcma_in_mm

Aug 24, 20243 min read

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🌱 created from: multiple myeloma (MM)

bcma_in_mm

B-cell maturation antigen (BCMA) in multiple myeloma

BCMA’s Role in Multiple Myeloma

BCMA is a member of the tumor necrosis factor receptor superfamily and is primarily found on mature B lymphocytes and plasma cells. Its expression is minimal in normal tissues, which helps to reduce the risk of off-target effects when targeting this antigen with therapies. This selective expression underlines the potential of BCMA as a therapeutic target, especially since multiple myeloma remains an incurable disease, with many patients experiencing relapse after initial treatments[1][2][4].

Therapeutic Approaches Targeting BCMA

Several innovative therapies targeting BCMA have been developed, each employing different mechanisms:

  1. Chimeric Antigen Receptor (CAR) T-cell Therapy: This personalized approach involves modifying a patient’s T cells to recognize and attack cancer cells expressing BCMA. Clinical trials have shown promising results, with high overall response rates (ORR) and significant reductions in minimal residual disease (MRD) in heavily pretreated patients[2][3][4].

  2. Antibody-Drug Conjugates (ADCs): These therapies combine antibodies that specifically bind to BCMA with cytotoxic agents. One such ADC, Belantamab mafodotin, has been approved for use in patients with highly refractory MM, demonstrating efficacy in clinical trials[3][5].

  3. Bispecific T-cell Engagers (BiTEs): These are engineered molecules that can simultaneously bind to BCMA on myeloma cells and activate T cells, effectively redirecting the immune response against the cancer. Preliminary studies have indicated that BiTEs can achieve significant clinical responses in relapsed or refractory cases[2][4].

Currently available drugs targeting B-cell maturation antigen (BCMA) in multiple myeloma include

  1. Belantamab mafodotin (GSK2857916): An antibody-drug conjugate (ADC) that delivers a cytotoxic agent directly to BCMA-expressing cells, approved for heavily refractory multiple myeloma.

  2. Teclistamab: A bispecific T-cell engager (BiTE) that redirects T cells to target BCMA on myeloma cells, administered subcutaneously.

  3. Idecabtagene vicleucel (Abecma): A CAR-T cell therapy that targets BCMA, providing a single intravenous infusion for patients with relapsed or refractory multiple myeloma.

  4. Ciltacabtagene autoleucel (Carvykti): Another CAR-T cell therapy targeting BCMA, which has shown significant efficacy in clinical trials and is administered as a single infusion[1][2][5].

These therapies represent significant advancements in the treatment of multiple myeloma, particularly for patients who have not responded to other treatments.

Citations: [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10099603/ [2] https://jhoonline.biomedcentral.com/articles/10.1186/s13045-020-00962-7 [3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472544/ [4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10137208/ [5] https://www.jnj.com/media-center/press-releases/carvykti-is-the-first-and-only-bcma-targeted-treatment-approved-by-the-u-s-fda-for-patients-with-relapsed-or-refractory-multiple-myeloma-who-have-received-at-least-one-prior-line-of-therapy [6] https://www.nature.com/articles/s41375-020-0734-z [7] https://www.bms.com/life-and-science/science/bcma-targeted-therapies-for-multiple-myeloma.html [8] https://ashpublications.org/blood/article/141/3/211/494080/Sequencing-anti-BCMA-therapies-in-myeloma

Clinical Outcomes and Future Directions

Current research indicates that BCMA-targeted therapies can lead to deep and durable responses in multiple myeloma patients. Studies have reported high rates of MRD negativity, which is associated with prolonged remission periods. However, challenges remain, including the potential for BCMA antigen loss, which can lead to resistance and disease relapse[3][4][5].

The ongoing exploration of BCMA-targeted therapies aims to refine these approaches and potentially expand their use to earlier lines of treatment in newly diagnosed patients. The combination of BCMA-targeted therapies with other novel agents, such as those targeting GPRC5D, is also being investigated to enhance treatment efficacy and overcome resistance mechanisms[1][2].

In conclusion, BCMA represents a promising target in the evolving landscape of multiple myeloma treatment, with several therapeutic modalities showing significant potential to improve patient outcomes. Continued research and clinical trials will be essential to fully realize the benefits of these innovative therapies.

Citations: [1] https://www.bms.com/life-and-science/science/bcma-targeted-therapies-for-multiple-myeloma.html [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472544/ [3] https://jhoonline.biomedcentral.com/articles/10.1186/s13045-020-00962-7 [4] https://www.nature.com/articles/s41375-020-0734-z [5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10099603/ [6] https://ashpublications.org/blood/article/141/3/211/494080/Sequencing-anti-BCMA-therapies-in-myeloma [7] https://www.nature.com/articles/s41467-024-44873-4 [8] https://www.mdanderson.org/cancerwise/your-questions-about-bcma-and-multiple-myeloma—answered.h00-159619434.html

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