BCMA in myeloma, that is to say B-cell maturation antigen is an antigen that is highly-expressed on the surface of MM cells.
“An antigen is any substance that causes the body to make an immune response against that substance. Antigens include toxins, chemicals, bacteria, viruses, or other substances that come from outside the body.”
If this antigen is commonly found on the surface of MM cells, then it becomes a possible target (therapy) for potentially killing the MM cell as well as a possible target for diagnosing a MM patient’s level of disease.
What is B-cell maturation antigen to myeloma management?
Here’s how BCMA is relevant to multiple myeloma management:
1. Target for Immunotherapies
BCMA is expressed almost exclusively on plasma cells (the cells that turn cancerous in multiple myeloma) and a subset of B cells. It is rarely found on other tissues, making it an ideal target for treatments. In recent years, this has led to the development of several novel immunotherapies targeting BCMA in myeloma management:
- CAR-T Cell Therapy: In this approach, a patient’s T-cells are collected, genetically modified to express receptors targeting BCMA, and then reinfused to attack myeloma cells. An example is idecabtagene vicleucel (Abecma), one of the FDA-approved BCMA CAR-T therapies.
- Bispecific Antibodies: These are engineered antibodies that bind both BCMA and CD3 (found on T cells). By bringing T cells into close proximity with myeloma cells, they can enhance the immune system’s ability to destroy cancer cells. An example of a bispecific antibody targeting BCMA is teclistamab.
- Antibody-Drug Conjugates (ADCs): Drugs like belantamab mafodotin use an anti-BCMA antibody linked to a cytotoxic agent. The antibody directs the drug to the myeloma cells, where the toxin can be released, killing the cancer cells.
2. Potential for Durable Responses
BCMA-targeted therapies have demonstrated promising results, especially in patients with relapsed/refractory multiple myeloma. These therapies have provided durable responses where traditional treatments, like chemotherapy, often fail.
3. Ongoing Research
Research into BCMA is ongoing, aiming to improve the safety and efficacy of these therapies. Efforts are underway to reduce side effects like cytokine release syndrome (CRS) and neurotoxicity, common with CAR-T therapy.
As a long-term survivor of myeloma, I take a cautiously optimistic view of all “new” MM therapies. While oncology has been studying BCMA since the 1990’s, FDA approval of the first CAR-T therapy, for example, was in 2017.
As of the writing of this post (2024), BCMA therapies are used for relapsed/refractory MM patients. In effect, these therapies are used to buy the MM patient more time. As BCMA therapies get better, I hope to document fewer side effects, longer remissions and lower costs.
In the meantime, send your questions to me at David.PeopleBeatingCancer@gmail.com
Thank you,
David Emerson
- MM Survivor
- MM Cancer Coach
- Director PeopleBeatingCancer
“A type of white blood cell that makes antibodies. B lymphocytes are part of the immune system and develop from stem cells in the bone marrow. Also called B cell…”
“The field of myeloma treatment in refractory or relapsed patients after standard therapy entered a new era due to the B-cell maturation antigen (BMCA) targeted approach.
BCMA is a member of the tumor necrosis factor receptor family with high expression in mature B-lymphocytes and plasma cells. Given the understanding of BCMA mechanism of action in MM, BCMA plays a promising role as a therapeutic target.
Several clinical trials are underway to evolve the current BCMA targeted treatment concept such as:
- antibody-drug conjugates (ADCs),
- bispecific T cell engagers (BITEs)
- and chimeric antigen receptor (CAR) T cell therapy.
This comprehensive review will give an update on various BMCA targeted treatment modalities (ADCs, BITEs, CAR T cell therapy) and its existing results on efficacy and safety from preclinical and clinical trials…
Currently, no approved diagnostic kit for the measurement sBCMA to diagnose or monitor MM patients is routinely available and the potential influence of anti-BCMA treatment on BCMA-expression is not quite clear; therefore, current existing conventional biomarkers in MM will still be the gold standard [23]…
Conclusions
Despite the enlarged armamentarium of different therapy options (e.g., PIs, IMiDs, and monoclonal antibodies) in recent years, MM is still an incurable disease that needs continuous therapy improvements.
The discovery of BCMA offers a new era in the field of immunotherapy in anti-myeloma therapy, including
- ADC,
- anti-BCMA/CD3 bispecific antibodies or anti-BCMA CAR-T cell therapy.
Early clinical trials of BCMA-targeted immunotherapies offered promising results in efficacy and tolerable side effects in RRMM patients with several prior therapy lines.
Therapy decision-making in patients with MM should be based on patient-related factors (e.g., patients’ preference, comorbidities) and disease-related risk factors (biological MM features, numbers and type of prior therapies, access to novel agents) to balance effectivity and toxicities.
Based on these considerations, an important matter is the decision for appropriate anti-BCMA immunotherapy options.”
