Beyond the Diagnosis: A Stage-by-Stage Guide to Multiple Myeloma Treatment

Here are educational overviews of the different stages of multiple myeloma, designed to help a patient understand their diagnosis and treatment journey.

Understanding Multiple Myeloma

Multiple myeloma is a cancer of plasma cells, a type of white blood cell found in the bone marrow. Healthy plasma cells are crucial for producing antibodies to fight infection. In multiple myeloma, these cells become cancerous and multiply uncontrollably, crowding out healthy blood cells and producing an abnormal protein called M-protein. This can lead to a variety of health problems, including bone damage, kidney issues, and weakened immunity.

Diagnosing a patient with multiple myeloma requires the integration of multiple data points, including blood work, pathology results, and imaging studies. Dr Amrita Krishnan and Cherry Rudge, a nurse practitioner, discuss the multifaceted diagnostic process for multiple myeloma in a recent CURE Connections, emphasizing the integration of blood tests, genetic and imaging assessments, and patient education to guide personalized treatment planning and enhance patient engagement in care.

Stage I: What is Smoldering Multiple Myeloma?

Smoldering multiple myeloma is a precancerous condition. Patients at this stage have a high number of M-proteins or a high percentage of myeloma cells in their bone marrow, but they do not show any symptoms or signs of organ damage from the disease. This is often an incidental finding from a routine blood test.

Key Features of Smoldering Myeloma:

• No symptoms: Patients feel completely healthy. There is no evidence of bone lesions, kidney damage, high blood calcium, or anemia.
• Active surveillance: The standard approach for smoldering myeloma is active surveillance, not immediate treatment. This involves regular monitoring with blood tests, urine tests, and sometimes bone surveys or imaging.
• Risk of progression: While not all cases of smoldering myeloma will progress to active multiple myeloma, there is a risk. Your oncologist will discuss your specific risk factors to determine how often you should be monitored.
• Goal: The primary goal at this stage is to monitor for any signs of progression to active disease. This avoids the side effects of unnecessary treatment while maintaining a high quality of life.

Treatment Overview of Smoldering Myeloma

• Standard of care: Active Surveillance ("watch and wait"): For most patients with smoldering myeloma, the standard approach is active surveillance, not immediate treatment. This involves regular monitoring with blood tests, urine tests, and sometimes imaging studies (like bone surveys or PET scans) to check for any signs of progression. The goal is to avoid the side effects of unnecessary treatment while maintaining a high quality of life.
• Why active surveillance? The risk of progression from smoldering myeloma to active myeloma can be low, and not all cases will progress. Unnecessary treatment exposes patients to potential side effects of powerful drugs without a clear benefit at this early stage.
• Clinical trials and high-risk smoldering myeloma: For patients with "high-risk" smoldering myeloma — meaning they have certain features that make them more likely to progress quickly — some oncologists may recommend participation in a clinical trial. These trials investigate whether early treatment can delay or prevent the progression to active multiple myeloma. Your doctor can discuss if this is a suitable option for you based on your specific risk factors.

Stage 2 and 3: How Do You Define Active Multiple Myeloma?

Active multiple myeloma is diagnosed when a patient with myeloma cells or M-protein shows at least one of the following signs of organ damage, often referred to by the acronym CRAB. CRAB is broken down by the following:

• Calcium elevation (hypercalcemia)
• Renal (kidney) failure
• Anemia (low red blood cell count)
• Bone lesions (bone fractures or lytic lesions)

Key features:

• Symptoms: This is where you might start feeling symptoms like bone pain, especially in the back or ribs, fatigue from anemia, or general weakness.
• Treatment is necessary: Unlike smoldering myeloma, active multiple myeloma requires immediate and aggressive treatment. The goal is to control the cancer, alleviate symptoms, and achieve remission.
• Initial treatment (induction): The first phase of treatment is called induction therapy. This often involves a combination of different drugs, like proteasome inhibitors, immunomodulatory drugs, and steroids, to kill the myeloma cells.
• Stem cell transplant: For eligible patients, a stem cell transplant, specifically an autologous stem cell transplant using your own cells, is often considered after induction therapy to achieve a deeper and longer-lasting remission.
• Maintenance therapy: Following a transplant or initial therapy, many patients will go on to a maintenance therapy regimen with a single drug to prevent the cancer from returning.
• Goal: The immediate goal is to reduce the myeloma cell burden, control symptoms, and aim for a complete or partial remission. The long-term goal is to manage the disease as a chronic condition.

Treatment Overview for Active Multiple Myeloma

• Initial treatment (induction therapy): The first phase of treatment is called induction therapy. This typically involves a combination of three or four different drugs to rapidly reduce the number of myeloma cells. Common drug classes used in these combinations include:
  • Proteasome inhibitors: (e.g., Velcade [bortezomib], Kyprolis [carfilzomib]) that block the disposal of old proteins, causing myeloma cells to die.
  • Immunomodulatory drugs (IMiDs): (e.g., Revlimid [lenalidomide], Pomalyst [pomalidomide]) that help the immune system attack the cancer cells.
  • Monoclonal antibodies: (e.g., Darzalex [daratumumab], Sarclisa [isatuximab]) that are engineered to attach to specific proteins on the surface of myeloma cells, marking them for destruction by the immune system.
  • Corticosteroids: (e.g., dexamethasone) that are highly effective at killing myeloma cells and can help manage side effects of other drugs.
• Stem cell transplant (SCT): For eligible patients, a high-dose chemotherapy and autologous stem cell transplant is often a key part of the treatment plan. This procedure:
  1. Your own stem cells are collected and stored.
  2. You receive very high doses of chemotherapy to kill any remaining myeloma cells.
  3. Your collected stem cells are infused back into your body to repopulate the bone marrow and restore blood cell production.
• Maintenance Therapy: After induction therapy, with or without a stem cell transplant, many patients will start a long-term, low-dose maintenance therapy. This is typically a single drug (most often lenalidomide) taken over a prolonged period to prevent the cancer from returning and to keep it in a state of remission.
• Supportive Care: This is a crucial part of the treatment plan and focuses on managing symptoms and preventing complications. It may include:
  • Bisphosphonates (e.g., zoledronic acid) to strengthen bones and prevent fractures.
  • Medications to manage anemia, kidney issues, or infections.

Relapsed/Refractory Multiple Myeloma

A relapse occurs when the myeloma returns after a period of remission. Refractory disease is when the myeloma either doesn’t respond to treatment or progresses while the patient is still on therapy. This is a common part of the multiple myeloma journey, as the cancer cells can adapt over time.

Key Features of Relapsed/Refractory Multiple Myeloma

• Change in strategy: Your oncologist will likely change your treatment regimen. This might involve using different drug combinations, a new class of medication, or considering clinical trials.
• Emerging therapies: The good news is that there are many new and effective treatments being developed, including CAR T-cell therapy and bispecific antibodies, which harness the body's own immune system to fight the cancer.
• Symptom management: Symptom management is a key focus. If you're experiencing new bone pain, fatigue, or other issues, it's important to discuss them with your care team.
• Goal: The goal in this phase is to regain control of the disease, manage any symptoms, and find a new treatment plan that is effective and tolerable for you. It's an ongoing conversation between you and your doctor about the best path forward.

Treatment Overview for Relapsed/Refractory Multiple Myeloma

• Change in strategy: The treatment approach changes based on what previous therapies you have received. The goal is to find a new combination of drugs that the cancer has not been exposed to or has not become resistant to. This might involve:
  • Switching drug combinations: For example, if you were on a combination of a proteasome inhibitor and an IMiD, your doctor might switch to a different combination or add a monoclonal antibody.
  • Reusing previous treatments: If you had a long remission after a particular treatment, your doctor may consider reusing it.
• Novel therapies: This is an exciting and rapidly evolving area of multiple myeloma treatment. Newer therapies, often used for relapsed/refractory disease, include:
  • Bispecific antibodies: These are "off-the-shelf" drugs that have two arms. One arm attaches to a myeloma cell and the other attaches to an immune T-cell, bringing them together so the T-cell can directly attack and kill the cancer cell. (e.g., Tecvayli [teclistamab], Talvey [talquetamab]).
  • CAR T-cell therapy: This is a personalized cellular therapy. Your own T cells are collected, genetically modified in a lab to recognize and attack your myeloma cells, and then infused back into your body. While effective, it's a complex process that takes time to prepare. (e.g., Abecma [idecabtagene vicleucel], Carvykti [ciltacabtagene autoleucel]).
  • Xpovio (Selinexor): A newer class of drug that blocks a protein in the cell's nucleus, causing myeloma cells to die.
  • Venclexta (Venetoclax): A targeted therapy used for a specific genetic subtype of multiple myeloma.
• Clinical trials: When standard therapies are no longer effective, clinical trials are an excellent option. They provide access to the newest and most promising treatments before they are widely available. Your oncologist can help you identify and enroll in a clinical trial that is right for you.

Editor's note: Your personal experience will be unique. By using this information as a foundation for your discussions, you can partner with your oncologist to make the best decisions for your health.

This article is for informational purposes only and is not a substitute for professional medical advice. Please contact your healthcare team with any questions or concerns.

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