Recently Diagnosed or Relapsed? Stop Looking For a Miracle Cure, and Use Evidence-Based Therapies To Enhance Your Treatment and Prolong Your Remission
Multiple Myeloma an incurable disease, but I have spent the last 25 years in remission using a blend of conventional oncology and evidence-based nutrition, supplementation, and lifestyle therapies from peer-reviewed studies that your oncologist probably hasn't told you about.
Click the orange button to the right to learn more about what you can start doing today.
- You are here:
- Home »
- Blog »
- Multiple Myeloma »
- Anti-BCMA Therapies for Myeloma
Anti-BCMA Therapies for Myeloma
Anti-BCMA therapies for myeloma is the next treatment step in the ongoing battle to manage our incurable blood cancer.
To refresh readers’ memories:
- corticosteroid (dexamethasone)
- proteasome inhibitors (PI), (velcade)
- immunomodulatory drugs (IMiDs), (revlimid)
- and anti-CD38 monoclonal antibodies (mAbs) (darzelex)…
Have been developed, trials, approved and prescribed to MM patients for the past 20 or so years.
The most recent class of chemotherapy regimens to kill MM are anti-BCMA therapies for myeloma as explained below
Thank you Drs. Munshi and Hari
What are the pros and cons of anti-BCMA therapies for the treatment of multiple myeloma?
Pros of Anti-BCMA Therapies in Multiple Myeloma
- High Efficacy in Relapsed/Refractory MM:
- Anti-BCMA therapies have shown remarkable efficacy in patients with multiple myeloma who have failed other treatments. This includes CAR-T cell therapy (like idecabtagene vicleucel and ciltacabtagene autoleucel), bispecific antibodies, and antibody-drug conjugates (ADCs).
- Patients who have undergone multiple lines of treatment often achieve deep responses, including complete or very good partial responses.
- Targeted Therapy:
- BCMA is highly expressed on malignant plasma cells, but not significantly on other tissues, allowing for selective targeting of cancerous cells with minimal impact on healthy cells.
- Durable Responses:
- Some patients experience long-lasting remissions. CAR-T therapies in particular have led to durable responses that can extend for months or even years in heavily pretreated patients.
- Expanding Options:
- Multiple approaches to anti-BCMA therapy (e.g., CAR-T, bispecific T-cell engagers (BiTEs), ADCs) provide options for patients who may not be eligible for one form but could benefit from another.
- Bispecific antibodies (like teclistamab) are off-the-shelf treatments, unlike CAR-T, which requires patient-specific cell engineering.
- Personalized Immunotherapy:
- CAR-T therapies allow for personalized treatment by engineering the patient’s own T-cells to attack their cancer, leading to a customized immune response.
Cons of Anti-BCMA Therapies in Multiple Myeloma
- Side Effects:
- Cytokine Release Syndrome (CRS): A common and potentially serious side effect, especially with CAR-T therapies, characterized by fever, low blood pressure, and organ dysfunction due to excessive immune activation.
- Neurotoxicity: Some patients experience neurological symptoms such as confusion, seizures, or coma, particularly with CAR-T therapy.
- Myelosuppression: Lowered blood counts (anemia, thrombocytopenia, neutropenia) are common and can increase the risk of infections and bleeding.
- Infections: Anti-BCMA therapies, particularly CAR-T and bispecific antibodies, can lead to immune suppression, increasing the risk of serious infections.
- Limited Accessibility:
- CAR-T therapies, in particular, are highly complex and resource-intensive, requiring specialized centers for manufacturing and administration.
- Long waiting times and limited availability can make it difficult for patients to access these treatments.
- Relapse and Resistance:
- Over time, some patients develop BCMA-negative clones or downregulate BCMA expression, leading to resistance to anti-BCMA therapies.
- Even in patients with good initial responses, relapse can occur, sometimes after a short duration of remission.
- Cost:
- Anti-BCMA therapies, especially CAR-T, are extremely expensive, often costing hundreds of thousands of dollars per treatment. This limits accessibility for many patients and strains healthcare systems.
- Logistical Challenges with CAR-T Therapy:
- CAR-T therapy requires patient-specific cell collection, modification, and reinfusion, which can take several weeks. During this time, patients may experience disease progression, making the logistics difficult in advanced cases.
- Limited Long-term Data:
- Although initial results are promising, long-term efficacy and safety data are still lacking. It’s unclear how durable the responses are in the long run and whether patients will experience significant late-stage complications.
As a long-term myeloma survivor who will probably die of one of my therapy-induced side effects, I have to stress the importance of the MM patient’s immune system. Successive remissions and relapsed with multiple limes of toxicity beat the patient’s immune system again and again until the patient is almost as susceptible to infection as she/he is to the raviges of MM.
This post’s focus was simply to outline anti-BCMA therapies for myeloma. Future posts will examine specific anti-BCMA regimens as well as short long-term and late stage side effects these therapies.
Email me with questions about what you have read on PeopleBeatingCancer. My email address is David.PeopleBeatingCancer@gmail.com
Thank you,
David Emerson
- MM Survivor
- MM Cancer Coach
- Director PeopleBeatingCancer
Anti-BCMA novel therapies for multiple myeloma
“The BCMA antigen is highly expressed in myeloma cells, thus representing a target for novel therapies. Several agents that target BCMA through different mechanisms, including:
- bispecific T cell engagers
- drug conjugated to antibody
- and CAR-T cells,
are now available or under development…
Novel therapies such as:
- proteasome inhibitors (PI), (velcade)
- immunomodulatory drugs (IMiDs), (revlimid)
- and anti-CD38 monoclonal antibodies (mAbs) (darzelex)…
have significantly improved treatment outcomes of newly diagnosed MM patients with a continuous increase of the overall survival (OS) that today reaches a median of 10 years[2–9]
However, MM patients still do relapse and MM is considered an incurable disease[10,11]. In particular, triple-class refractory (refractory to PI, IMiDs, and anti-CD38 antibody) and penta-refractory (first and second-generation PIs, two generations of IMiDs, anti-CD38 antibody) patients have a median OS of 5.6 months, especially in the presence of high-risk cytogenetics (HR)[12–20] or positive minimal residual disease[21–26]. Therefore, novel therapies, especially for relapsed/refractory myeloma patients (RRMM), are necessary[25–26].
BCMA is overexpressed in myeloma PCs compared to normal ones, and its expression levels are elevated regardless of the stage of MGUS (monoclonal gammopathy of undetermined significance), SMM (smoldering multiple myeloma), and symptomatic MM[40–41]…
BCMA antibody drug conjugates
Antibody-drug conjugate (ADC) consists of a monoclonal antibody directed against a tumor- antigen and a cytotoxic agent inducing cell death (payload). ADC is internalized after binding to the related antigen on the tumor cell’s surface, then the linker is hydrolyzed inside of the lysosomes or endosomes and the payloads are released to cause cell death.
ADCs can selectively target malignant cells with great efficiency on tumor cells and limited toxicities. Auristatin is a tubulin polymerase inhibitor used as a payload for MM[55–60]…
BCMA bispecifics
BITEs are bispecific T cell engagers and represent a different modality of immunotherapy targeting BCMA…
Others BITEs currently studied are
- Elranatamab (PF-06863135),
- ABBV-383, and
- alnuctamab (CC-93269)…
BCMA CAR-Ts
CART (Chimeric antigen receptor T) cell therapy act as cell-mediated immunotherapy. Briefly, after an in vitro gene transfer strategy, the patient’s T cells acquire the ability to recognize tumor antigens (mostly used is BCMA) on MM plasma cells and thus destroy them…
DISCUSSION
Despite novel therapeutic advantages in recent years, MM remains incurable. BCMA immunotherapies are a novel anti-MM therapeutic approach that holds promise to improve MM survival in the future. ADCs, BITEs, and CAR-T cells are the newest therapeutic options targeting BCMA…
In conclusion, therapies that target BCMA will play an important role in MM therapy, with the ambitious purpose of improving the cure rate; however, further investigations are still necessary to better define their real impact in clinical practice.