When myeloma comes back, a different arsenal of weapons is needed to fight back against the cancer. There are a number of reasons why a relapse is so difficult. The myeloma cells that remain to cause relapse are typically the most resistant. Plus, the mutations are more numerous.
As Dr. Paul Richardson, Director of Clinical Research at Dana-Farber Cancer Institute’s Multiple Myeloma Center, explains, “We’ve shown this in our clinical trials that when, for example, a patient presents with newly diagnosed myeloma and we interrogate the genetics of their cancer, we see over 5,000 mutations.” But in the same patient who undergoes therapy but relapses “that patient is found to have 12,000 mutations in their disease.” A larger number of mutations in cancer cells means drugs will likely be less effective because there is greater resistance to therapies.
These stronger relapsed cells, Dr. Richardson says, require powerful combination therapies. “You have to have that much more potent strategies to overcome resistance and exert better disease control. In our trials we’ve shown that three drugs are better than two, but that doesn’t always apply because it depends on tolerability as well.”
Each drug that patients take has a chance of side effects, including nausea, vomiting, swelling of the limbs and skin, liver problems, and numbness. As patients increase the number of drugs they take, the chance of these side effects occurring rises. Thus, although three drug combinations are typically better than two in treating relapsed myeloma, that depends on the individual patient’s ability to tolerate them. Despite this increased risk of toxicity, recent evidence suggests that four drugs may even be more effective than three drugs in treating relapsed myeloma. “We’re now realizing four drugs–in other words, three drugs plus an antibody or plus another drug–may actually be the way to go,” explains Dr. Richardson.
These drugs include:
- Proteasome inhibitors–these disrupt the mechanism by which cancer cells break down proteins internally. This build-up of protein within the cell eventually causes the cells to die.
- Immunomodulatory drugs–these activate your immune system to target cancer cells and kill them like they would any other infection.
- Monoclonal antibodies–these are single, specific proteins that initiate a variety of cancer-fighting process within the body, including recruitment of immune cells to the cancerous area. One typical example is Dara (daratumumab).
- Next generation small molecules–these are generalized drugs that kill cancer cells by inducing cell death (like the drug Venetoclax) or by inhibiting gene expression (HDACs).
By combining these various drugs, relapsed myeloma can be tackled in multiple different ways and lead to better outcomes.
Learn more about SurvivorNet's rigorous medical review process.
Dr. Paul Richardson is the Clinical Program Leader and Director of the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute. Read More
When myeloma comes back, a different arsenal of weapons is needed to fight back against the cancer. There are a number of reasons why a relapse is so difficult. The myeloma cells that remain to cause relapse are typically the most resistant. Plus, the mutations are more numerous.
As Dr. Paul Richardson, Director of Clinical Research at Dana-Farber Cancer Institute’s Multiple Myeloma Center, explains, “We’ve shown this in our clinical trials that when, for example, a patient presents with newly diagnosed myeloma and we interrogate the genetics of their cancer, we see over 5,000 mutations.” But in the same patient who undergoes therapy but relapses “that patient is found to have 12,000 mutations in their disease.” A larger number of mutations in cancer cells means drugs will likely be less effective because there is greater resistance to therapies.
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These stronger relapsed cells, Dr. Richardson says, require powerful combination therapies. “You have to have that much more potent strategies to overcome resistance and exert better disease control. In our trials we’ve shown that three drugs are better than two, but that doesn’t always apply because it depends on tolerability as well.”
Each drug that patients take has a chance of side effects, including nausea, vomiting, swelling of the limbs and skin, liver problems, and numbness. As patients increase the number of drugs they take, the chance of these side effects occurring rises. Thus, although three drug combinations are typically better than two in treating relapsed myeloma, that depends on the individual patient’s ability to tolerate them. Despite this increased risk of toxicity, recent evidence suggests that four drugs may even be more effective than three drugs in treating relapsed myeloma. “We’re now realizing four drugs–in other words, three drugs plus an antibody or plus another drug–may actually be the way to go,” explains Dr. Richardson.
These drugs include:
- Proteasome inhibitors–these disrupt the mechanism by which cancer cells break down proteins internally. This build-up of protein within the cell eventually causes the cells to die.
- Immunomodulatory drugs–these activate your immune system to target cancer cells and kill them like they would any other infection.
- Monoclonal antibodies–these are single, specific proteins that initiate a variety of cancer-fighting process within the body, including recruitment of immune cells to the cancerous area. One typical example is Dara (daratumumab).
- Next generation small molecules–these are generalized drugs that kill cancer cells by inducing cell death (like the drug Venetoclax) or by inhibiting gene expression (HDACs).
By combining these various drugs, relapsed myeloma can be tackled in multiple different ways and lead to better outcomes.
Learn more about SurvivorNet's rigorous medical review process.
Dr. Paul Richardson is the Clinical Program Leader and Director of the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute. Read More
