Multiple myeloma is a type of blood cancer that affects plasma cells, which are responsible for producing antibodies. When plasma cells grow out of control, they can crowd out normal blood cells and cause various problems, such as bone pain, kidney damage, infections, and anemia.
Multiple myeloma is not a curable disease, but it can be treated with different therapies that can help control its growth, relieve symptoms, and improve quality of life. However, over time, multiple myeloma can become resistant to some treatments and require new ones.
This is where third line treatment for multiple myeloma comes in. Third line treatment is the term used for the therapy that is given after two previous lines of treatment have failed or stopped working. Above third line treatment for multiple myeloma refers to any therapy that is given after third line treatment has failed or stopped working.
In this blog, we will discuss what third line treatment for multiple myeloma options are available for multiple myeloma, how they work, what their benefits and risks are, and what factors may influence the choice of treatment. We will also share some tips on how to cope with multiple myeloma and its treatment, and some resources where you can find more information and support.
What are the third line treatment for multiple myeloma?
There are several options available in the third line treatment for multiple myeloma setting for patients. These include:
- Alkylating agents
- Pomalidomide-based therapy
- Carfilzomib-based therapy
- Retreatment with bortezomib
- Panobinostat in combination with bortezomib
Other treatment options for multiple myeloma include a combination of several treatments such as antibodies, chemotherapy, immunomodulatory drugs, novel mechanism of action drugs, proteasome inhibitors, and radiation therapy. A combination of several myeloma treatments, such as an immunomodulatory drug, a protease inhibitor, and a corticosteroid, may have greater success than one type of treatment alone.
Let’s take a closer look at each of these options and how they work.
Alkylating agents in third line treatment for multiple myeloma
Alkylating agents are a type of chemotherapy that works by damaging the DNA of cancer cells, preventing them from dividing. They have been used for third line treatment for multiple myeloma for a long time and are among the oldest and most widely used drugs. Examples of alkylating agents include melphalan, cyclophosphamide, and bendamustine.
Alkylating agents can be used alone or in combination with other drugs such as steroids, immunomodulatory drugs, or proteasome inhibitors. They can also be part of high-dose therapy followed by autologous stem cell transplantation (ASCT), which involves collecting the patient’s own stem cells, administering high-dose chemotherapy to eliminate remaining cancer cells, and then reintroducing the stem cells to restore blood production.
Alkylating agents have demonstrated efficacy in inducing responses in relapsed or refractory multiple myeloma patients, particularly those who have not been previously exposed or have had a long interval since their last exposure. However, they can cause significant side effects such as bone marrow suppression, nausea, vomiting, hair loss, infections, and secondary cancers. Additionally, over time, cancer cells can develop resistance mechanisms against these agents, reducing their effectiveness.
Therefore, alkylating agents are typically reserved for patients with limited options or who are ineligible for other therapies. They may also be considered for younger patients suitable for ASCT who have not been previously exposed or have had a long interval since their last exposure.
Pomalidomide-based therapy in third line treatment for multiple myeloma
Pomalidomide is an immunomodulatory drug (IMiD) that modulates the immune system and interferes with the growth and survival of cancer cells. It is similar to thalidomide and lenalidomide, which are also IMiDs used for multiple myeloma. However, pomalidomide has a distinct structure and mechanism of action, making it more potent and less toxic than its predecessors.
Pomalidomide is approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of relapsed or refractory multiple myeloma patients who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor. Typically, it is administered in combination with dexamethasone, a steroid that reduces inflammation and enhances the anti-myeloma effect of pomalidomide.
Pomalidomide-based therapy has demonstrated efficacy in inducing responses in relapsed or refractory multiple myeloma patients, even those who are resistant or intolerant to lenalidomide and bortezomib. It can also improve patient survival and quality of life. However, it may result in side effects such as low blood counts, infections, fatigue, constipation, and nerve damage. It is important to note that pomalidomide can cause birth defects and blood clots, necessitating careful monitoring and preventive measures.
Therefore, pomalidomide-based therapy in third line treatment for multiple myeloma is a valuable option for patients who have exhausted other treatments or have limited access to newer agents. Combining pomalidomide with other drugs, such as antibodies, proteasome inhibitors, or novel mechanisms of action drugs, may enhance its efficacy and overcome resistance.
Carfilzomib-based therapy in third line treatment for multiple myeloma
Carfilzomib is a proteasome inhibitor that blocks the proteasome, an enzyme complex responsible for breaking down proteins in cells. By inhibiting the proteasome, carfilzomib leads to the accumulation of toxic proteins in cancer cells, resulting in cell death. Unlike bortezomib and ixazomib, which are other proteasome inhibitors used in multiple myeloma, carfilzomib selectively and irreversibly binds to the proteasome.
Carfilzomib is approved by the FDA and the EMA for the treatment of relapsed or refractory multiple myeloma patients who have received at least one prior therapy. It can be administered with dexamethasone or in combination with lenalidomide and dexamethasone. It can also be combined with other drugs, such as antibodies, immunomodulatory drugs, or novel mechanism of action drugs.
Carfilzomib-based therapy has demonstrated efficacy in inducing responses in relapsed or refractory multiple myeloma patients, including those who are resistant or intolerant to bortezomib and lenalidomide. It can also improve patient survival and quality of life. However, it may cause side effects such as high blood pressure, heart problems, kidney problems, infections, nausea, diarrhea, and nerve damage. Additionally, it requires intravenous administration and frequent clinic visits.
Therefore, carfilzomib-based therapy in third line treatment for multiple myeloma shows promise as an option for patients who have progressed on other treatments or have access to newer agents. It may also serve as a foundation for combinations that enhance efficacy and overcome resistance.
Retreatment with bortezomib in third line treatment for multiple myeloma
Bortezomib is a proteasome inhibitor that functions by blocking the proteasome, an enzyme complex responsible for protein breakdown in cells. It was the first proteasome inhibitor approved for multiple myeloma and remains widely used in the treatment of the disease.
Bortezomib is approved by the FDA and the EMA for the treatment of newly diagnosed, relapsed, or refractory multiple myeloma. It can be administered as a single agent or in combination with steroids, immunomodulatory drugs, chemotherapy, or antibodies. It is also used in induction therapy before autologous stem cell transplantation (ASCT) and as maintenance therapy following ASCT.
Retreatment with bortezomib in third line treatment for multiple myeloma has shown efficacy in inducing responses in patients with newly diagnosed or relapsed/refractory multiple myeloma. It can also improve patient survival and quality of life. However, it may result in side effects such as low blood counts, infections, nerve damage, diarrhea, nausea, and skin reactions. Additionally, over time, cancer cells may develop resistance mechanisms, reducing the effectiveness of bortezomib.
Therefore, retreatment with bortezomib may be considered for patients who previously responded well to the drug and have had a substantial time interval since their last exposure. It can also be combined with other drugs to enhance efficacy and overcome resistance.
Panobinostat in combination with bortezomib
Panobinostat is a novel mechanism of action drug that works by inhibiting histone deacetylases (HDACs), which are enzymes that regulate gene expression in cells. By inhibiting HDACs, panobinostat alters the expression of genes that control cell growth, survival, and death. It is given with bortezomib and dexamethasone to treat multiple myeloma that has relapsed or become refractory after at least two prior therapies including bortezomib and an IMiD.
Panobinostat in combination with bortezomib in third line treatment for multiple myeloma can improve survival and delay disease progression in patients with relapsed or refractory multiple myeloma. However, it can also cause side effects such as low blood counts, infections, fatigue, diarrhea, nausea, vomiting, loss of appetite, weight loss, rash, nerve damage, and increased risk of bleeding and heart problems.
How is the choice of third line treatment for multiple myeloma made?
The choice of third line treatment for multiple myeloma depends on several factors, such as:
- The type and stage of multiple myeloma
- The previous treatments used and their outcomes
- The genetic features of the myeloma cells
- The patient’s age, overall health, and preferences
- The availability and cost of the treatments
- The potential benefits and risks of the treatments
There is no one-size-fits-all approach to third line treatment for multiple myeloma. Each patient’s situation is unique and requires a personalized plan that balances the goals of treatment with the quality of life. Therefore, it is important to discuss the options with your doctor and make an informed decision based on your values and expectations.
How to cope with multiple myeloma and its treatment?
Living with multiple myeloma and its treatment can be challenging physically, emotionally, mentally, and socially. However, there are some strategies that can help you cope better and improve your well-being. Here are some tips:
- Learn as much as you can about your disease and its treatment. Knowledge is power and can help you feel more in control of your situation. Ask your doctor questions, seek reliable sources of information, and join support groups or online communities where you can share your experiences and learn from others.
- Follow your treatment plan as prescribed by your doctor. Take your medications as directed, keep your appointments, report any side effects or changes in your condition, and follow any recommendations for tests or procedures. This can help you get the best results from your treatment and avoid complications.
- Manage your symptoms and side effects. Talk to your doctor about ways to prevent or relieve symptoms such as pain, fatigue, nausea, constipation, nerve damage, infections, etc. You may be prescribed medications or other therapies to help you cope. You can also try some self-care measures such as resting when needed, eating a balanced diet, drinking plenty of fluids, exercising moderately, practicing relaxation techniques, etc.
- Seek emotional support. Living with multiple myeloma can be stressful and overwhelming at times. You may experience a range of emotions such as fear, anger, sadness, guilt, anxiety, depression, etc. It is normal to have these feelings and it is important to express them in healthy ways. You can talk to your family members, friends, counselor, spiritual advisor, or anyone you trust about how you feel. You can also join a support group or online community where you can connect with other people who understand what you are going through.
- Maintain a positive outlook. While it may not be easy to stay optimistic when facing multiple myeloma and its treatment, it can help you cope better and improve your quality of life. Try to focus on the things that give you hope, joy, and meaning in life. Celebrate your achievements, no matter how small they may seem. Appreciate the support you receive from others. Find humor in the situations you encounter. Practice gratitude for the things you have. Remember that you are not alone and that you can overcome the challenges you face.
- Seek professional help if needed. Sometimes, coping with multiple myeloma and its treatment can be too much to handle on your own. You may experience severe or persistent symptoms or side effects that interfere with your daily functioning. You may also develop mental health problems such as depression, anxiety, or post-traumatic stress disorder (PTSD) that affect your mood, thoughts, and behavior. If this happens, do not hesitate to seek professional help from your doctor, a psychologist, a psychiatrist, or a social worker. They can provide you with the appropriate treatment and support you need to improve your physical and mental health.
Where to find more information and support?
If you want to learn more about third line treatment for multiple myeloma, or if you need more support in coping with your disease and its treatment, here are some resources that you may find helpful:
- The International Myeloma Foundation (IMF) is a global organization that provides education, advocacy, and support for people affected by multiple myeloma. It offers various programs and services such as publications, webinars, podcasts, clinical trials, research grants, hotline, peer-to-peer network, support groups, etc.
- The Multiple Myeloma Research Foundation (MMRF) is a nonprofit organization that funds and facilitates research to find a cure for multiple myeloma. It also provides information, resources, and tools for patients and caregivers to navigate their disease and treatment journey.
- The Leukemia & Lymphoma Society (LLS) is a nonprofit organization that supports research, education, advocacy, and patient services for people affected by blood cancers such as multiple myeloma. It offers various programs and services such as booklets, videos, webcasts, newsletters, financial assistance, online chats, telephone support groups, etc.
- The American Cancer Society (ACS) is a nonprofit organization that provides information, support, and services for people affected by cancer of any type. It offers various programs and services such as online communities, helpline, road to recovery, hope lodge, tlc, etc.
Conclusion
Third line treatment for multiple myeloma is a complex and evolving field that offers hope and options for patients who have exhausted other therapies. However, it also poses challenges and risks that require careful consideration and discussion with your doctor. By learning about your disease and its treatment, following your treatment plan, managing your symptoms and side effects, seeking emotional support, maintaining a positive outlook, and seeking professional help if needed, you can cope better with multiple myeloma and its treatment and improve your quality of life.
