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BCG Maintenance Therapy for Myeloma?
Could Bacillus Calmette-Guérin (BCG) be a maintenance therapy for myeloma survivors? Or perhaps BCG can combine with another low-dose therapy, such as Revlimid, to enhance its efficacy?
Here is what ChatGPT thinks of my idea…
Could Bacillus Calmette-Guérin (BCG) be a maintenance therapy for myeloma?
Bacillus Calmette-Guérin (BCG), a live attenuated strain of Mycobacterium bovis, is most commonly used as:
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A vaccine for tuberculosis
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An intravesical immunotherapy for non-muscle-invasive bladder cancer
However, its potential as a maintenance therapy for multiple myeloma (MM) is not currently established in clinical practice or supported by major guidelines. That said, there are some theoretical and early experimental angles worth considering:
🔬 Potential Rationale for BCG in Myeloma
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Immunostimulation:
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BCG activates innate and adaptive immune responses, including macrophages, NK cells, and T cells, which could theoretically enhance immune surveillance against residual myeloma cells.
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“Trained immunity”:
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BCG is known to induce long-term epigenetic and metabolic changes in innate immune cells, enhancing their response to future stimuli. This concept has been explored in infections and some cancers.
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Historical interest:
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In the 1970s and 1980s, BCG was studied in a few trials for hematologic malignancies (including MM) with limited success and considerable toxicity. Most efforts were abandoned due to lack of sustained benefit.
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📚 Evidence and Studies
There is no robust, recent evidence showing that BCG provides benefit as a maintenance therapy in myeloma. Specifically:
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No phase II/III trials have demonstrated improved progression-free survival (PFS) or overall survival (OS) in MM patients receiving BCG maintenance.
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Any existing use is off-label and experimental, often in the context of immunomodulatory strategies or vaccine-like therapies under investigation.
🚫 Limitations and Risks
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Toxicity: Systemic use of BCG (especially in immunocompromised patients like those with MM) risks severe infections.
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Immune-related side effects: Inflammation, granulomas, and cytokine release can occur.
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Drug interactions: With immunosuppressive agents or maintenance therapies like lenalidomide or daratumumab.
✅ Current Standard of Care for MM Maintenance
Approved maintenance options post-induction or post-transplant include:
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Lenalidomide (mainstay, especially in standard-risk patients)
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Proteasome inhibitors (e.g., bortezomib) for high-risk cytogenetics
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Monoclonal antibodies (e.g., daratumumab) in some evolving regimens
🧪 Future Directions?
There is interest in:
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BCG-derived immunotherapies or modified bacterial vectors delivering tumor-associated antigens
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Checkpoint inhibitor combinations (though caution is needed due to past trial failures in MM)
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Myeloma vaccines using adjuvants like BCG or related compounds
🔍 Bottom Line
BCG is not a recommended or evidence-based maintenance therapy for multiple myeloma at this time. While its immunomodulatory effects are intriguing and under study in other cancers, more research would be needed to justify its use in MM, especially given the unique immune dysregulation and treatment landscape in this disease.
The term “maintenance therapy” implies the long-term use of the therapy. Long-term use of most any toxic therapy can be difficult. But short-term?
Maybe…
I am a long-term survivor of MM. I like to think outside the box. Email me with questions about your MM experiences- David.PeopleBeatingCancer@gmail.com
Hang in there,
David Emerson
- MM Survivor
- MM Cancer Coach
- Director PeopleBeatingCancer
BCG alters bone marrow to strengthen anti-cancer response
A new study reveals that BCG, a decades-old bladder cancer treatment, reprograms the immune system at the bone marrow level, offering a new perspective into how this immunotherapy boosts the body’s defence against cancer…
Over three decades ago, the US Food and Drug Administration (FDA) approved Bacillus Calmette-Guérin (BCG) as the first-ever immunotherapy for cancer, specifically for early-stage bladder cancer. Despite its age, BCG remains a crucial part of bladder cancer treatment. Now, new research from Weill Cornell Medicine and Memorial Sloan Kettering Cancer Center (MSK) is revealing a deeper understanding of how BCG works- findings that could change future immunotherapies.
New findings: BCG reprograms the immune system at its source
In a study published in Cancer Cell, Dr Glickman and his colleagues demonstrated that BCG’s effects go far beyond the bladder. The treatment reprograms bone marrow stem and progenitor cells, which boost the body’s ability to generate myeloid immune cells with enhanced cancer-fighting abilities.
“Now it’s clear it improves the innate immune system’s ability to fight cancer,” said Dr Steven Josefowicz, co-senior author and associate professor at Weill Cornell Medicine.
Unlike the adaptive immune system, which targets familiar threats, the innate immune system offers broad, rapid defence. The study revealed that BCG trains this innate system not just to respond to bacteria, but to better recognise and fight tumours…
Conclusion: a classic treatment, reinvented
This study moves our understanding forward for one of the most established immunotherapies in cancer treatment. By showing that BCG reprograms the body’s innate immune system at the bone marrow level, researchers have found a powerful mechanism that could enhance not only bladder cancer treatment but immunotherapy strategies as a whole.
As scientists continue to decode the immune system’s intricate workings, BCG’s surprising reach may allow for broader, more effective approaches to fighting cancer.
Tracking BCG’s pathway from bladder to bone marrow
Traditionally, it was believed that BCG’s immune effects were limited to the bladder, where it was introduced directly to tumours. But this study shows that BCG travels from the bladder to the bone marrow, where it reprograms hematopoietic stem and progenitor cells- the source of new immune cells.
Using a specialised technique called Progenitor Input Enrichment single-cell sequencing (PIE-seq), researchers traced how BCG altered gene activity in these stem cells in both mouse models and human patients. The result was new immune cells that emerged after BCG treatment were significantly more effective at fighting tumours.
“These findings show that this training of the innate immune system that happens with the BCG vaccine also happens in the context of bladder administration to treat cancer,” said Dr Gil Redelman-Sidi, infectious disease expert at MSK.
Chemoimmunotherapy for multiple myeloma
Abstract
The effect of chemoimmunotherapy consolidation treatment using alternating courses of alkylating agents and BCG was studied in 105 responding patients with multiple myeloma. The survival time of these patients was similar to that of responding patients treated on previous maintenance programs, indicating no apparent value from BCG for myeloma.
The duration of unmaintained remission was longest in those with low numbers of residual plasma cells, and relapse usually developed within one year in patients with persistent serum myeloma peaks.
Disease recontrol was achieved in 50% of relapsing patients whose median survival from retreatment was 20 months. Patient follow-up without chemotherapy until relapse was justified mainly for those responding patients with disappearance of myeloma proteins.
Bacillus Calmette-Guérin (BCG) be a maintenance therapy for myeloma
Bacillus Calmette-Guérin (BCG) be a maintenance therapy for myeloma