MULTIPLE MYELOMA

Multiple myeloma also called Kahler’s disease, is a type of blood cancer that originates in the plasma cells, a kind of white blood cell. Plasma cells play a vital role in the immune system by producing antibodies that help combat infections. However, in multiple myeloma, these cells become cancerous and multiply uncontrollably, leading to various health complications. While there’s no cure, treatments can slow its progress and sometimes alleviate symptoms.

What Happens in Multiple Myeloma?

Role of Plasma Cells: Plasma cells, a type of white blood cell, produce antibodies to fight infections.
Abnormal Cell Growth: In multiple myeloma, plasma cells grow uncontrollably, producing excess protein (immunoglobulin) that accumulates in the bones and blood, leading to organ damage.
Bone Impact: These abnormal cells crowd out normal blood cells in the bone marrow and release chemicals that cause other cells to erode bone tissue, creating weak spots known as lytic lesions.
Progression and Spread: As the disease advances, plasma cells can move beyond the bone marrow, causing further organ damage.

Other Plasma Cell Disorders

Multiple myeloma is part of a broader group of conditions affecting plasma cells. These include:

Monoclonal Gammopathy:
- General: Plasma cells produce too many copies of a single antibody.
- Multiple Myeloma: A specific form of monoclonal gammopathy.
- Monoclonal Gammopathy of Undetermined Significance (MGUS): A condition that increases the risk of developing multiple myeloma.
Solitary Plasmacytoma:
- Description: Similar to multiple myeloma but involves a single abnormal growth of plasma cells, either within or outside the bone.
- Risk: Can increase the likelihood of developing multiple myeloma.
Light Chain Amyloidosis:
- Characteristics: Involves abnormal plasma cells in the bone marrow but in fewer numbers compared to multiple myeloma.
Waldenstrom Macroglobulinemia:
- Nature: A blend of monoclonal gammopathy and non-Hodgkin’s lymphoma, affecting both plasma cells and lymphoid tissue.

Causes

The exact cause of multiple myeloma remains unclear. However, genetic mutations and changes in the bone marrow environment are believed to contribute to the development of this disease. Certain risk factors, such as exposure to radiation and chemicals, have also been implicated.

Prevalence

Multiple myeloma is relatively uncommon, accounting for about 1% of all cancers and approximately 10% of all hematologic malignancies. It predominantly affects older adults, with the average age of diagnosis being around 65 years. It is slightly more common in men than women and has a higher incidence in African American populations compared to other ethnic groups.

Symptoms

Initially, multiple myeloma might not cause any noticeable symptoms. As the disease progresses, you might experience:

Bone Pain: Persistent pain in the bones.
Weakness and Fatigue: General feelings of weakness and being easily tired.
Weight Loss and Loss of Appetite: Unexplained weight loss and reduced appetite.
Gastrointestinal Issues: Upset stomach and constipation.
Mental Confusion: Feeling confused or having trouble thinking clearly.
Frequent Infections: Increased susceptibility to infections.
Severe Thirst: Feeling extremely thirsty.
Neurological Symptoms: Weakness or numbness in the arms and legs.

Risk Factors

While the exact causes are not fully understood, several risk factors have been identified:

Age: Risk increases with age, particularly after 60.
Gender: Males are more likely to develop multiple myeloma.
Race: Higher incidence in African Americans.
Family History: A close relative with multiple myeloma increases risk.
Obesity: Linked to a higher risk of developing the disease.
Exposure to Chemicals and Radiation: Prior radiation exposure and Contact with certain chemicals, such as those used in rubber manufacturing, woodworking, firefighting, or herbicides.

Complications of Multiple Myeloma

Multiple myeloma can lead to several health issues:

Bone Problems:
- Weak Bones: Increased risk of fractures.
Blood Problems:
- Anemia: Insufficient red blood cells causing fatigue, paleness, and potential heart issues.
- Low Platelets: Difficulty in blood clotting.
Infections:
- Weak Immune System: Overproduction of ineffective antibodies crowds out healthy ones, making infections more common and harder to fight.
- White Blood Cell Deficiency: Further weakens the immune response.
Kidney Damage:
- Kidney Failure: Abnormal proteins can clog kidneys, impairing their function and potentially leading to kidney failure.

Diagnosis

Doctors might suspect multiple myeloma if routine blood tests reveal:

Hypercalcemia: Elevated calcium levels in the blood.
Anemia: A lower than normal count of red blood cells.
Kidney Issues: Signs of impaired kidney function.
Protein Imbalance: High total protein with low albumin levels, indicating a “globulin gap.”

To confirm the diagnosis, several tests are conducted:

Complete Blood Count (CBC): Measures various blood cell types.
Kidney Function Tests: Blood urea nitrogen (BUN) and creatinine levels to evaluate kidney health.
Protein Analysis: Blood and urine tests to detect and measure abnormal proteins.

If these tests suggest multiple myeloma, a bone marrow biopsy may follow. In this procedure, a needle extracts a sample of bone marrow, usually from the hip, to assess the plasma cell count.

Imaging Tests:

X-rays: Identify bone damage.
CT Scan, MRI, PET Scan: Provide detailed images to detect further complications.

Treatments for multiple myeloma

Doctors classify multiple myeloma based on genetic factors in the tumor cells, categorizing it as high, intermediate, or standard risk. This risk assessment influences treatment decisions.

Watchful Waiting: If you’re asymptomatic (no symptoms), your doctor might recommend close monitoring instead of immediate treatment.
Treatment Goals: Treatment aims to improve your quality of life by alleviating symptoms and ensuring proper nutrition.
High-Risk Cases: For high-risk cases, participation in clinical trials for new or existing treatments might be an option.

Treatment Options:

1. Medication Choices:

The choice of medications depends on factors such as age and the severity of the cancer.

A. Chemotherapy

Chemotherapy drugs are often administered in combinations. Some commonly used ones for multiple myeloma include:

Bendamustine (Treanda)
Cyclophosphamide (Cytoxan)
Doxorubicin (Adriamycin)
Etoposide (VP-16)
Liposomal doxorubicin (Doxil)
Melphalan (Alkeran, Evomela)
Vincristine (Oncovin)

B. Targeted Therapies

Targeted therapies focus on specific proteins, genes, or tissues to inhibit cancer growth. These include:

Monoclonal Antibodies: These help the immune system locate and destroy myeloma cells. Drugs like:
- Daratumumab (Darzalex)
- Elotuzumab (Empliciti)
- Isatuximab (Sarclissa)

If you don’t exhibit symptoms, your doctor might initiate treatment with targeted therapies to prevent the progression of myeloma.

Additional Targeted Medications

Proteasome Inhibitors: These medications disrupt the process that breaks down excess proteins within cells. Since myeloma cells produce an abundance of proteins, their accumulation leads to cell death. Drugs in this category include:
- Bortezomib (Velcade)
- Carfilzomib (Kyprolis)
- Ixazomib (Ninlaro)
Histone Deacetylase (HDAC) Inhibitors: Drugs like panobinostat (Farydak) influence gene activity within cells. Your doctor might prescribe these if previous treatments, such as bortezomib and another agent, were ineffective.
Nuclear Export Inhibitor
- Selinexor (Xpovio): This drug inhibits the nuclear export protein XPO1, effectively targeting tumor cells. FDA approval is granted for individuals who have undergone at least four prior unsuccessful treatments.
B-Cell Maturation Antigen (BCMA) Targeting Agents
- Belantamab Mafodotin-blmf (Blenrep): Classified as a BCMA inhibitor, Blenrep combines a monoclonal antibody with a toxin. It targets the protein shielding cancer cells, allowing the toxin to destroy them. It’s prescribed after failing at least four other therapies.
Bi-Specific T-Cell Engager (BiTE)
- Teclistamab-cqyv (Tecvayli): Tecvayli is a bispecific T-cell engager that targets BCMA. It functions by binding to both T cells and myeloma cells simultaneously, instigating an immune response against the cancer cells. It’s recommended after prior unsuccessful treatments.

C. Immunomodulatory Drugs

In addition to conventional treatments, several novel immunomodulatory drugs have shown promise in combating multiple myeloma. These drugs boost immune cell function, facilitating their attack on cancer cells. They also inhibit the formation of new blood vessels in the bone marrow, thereby depriving myeloma cells of vital nutrients. Notable medications include:

Lenalidomide (Revlimid)
Pomalidomide (Pomalyst)
Thalidomide (Thalomid)

D. Immunotherapy for Multiple Myeloma

Immunotherapy utilizes the body’s immune system to combat cancer cells, offering a promising approach in multiple myeloma treatment. Notable immunotherapeutic strategies include:

Chimeric Antigen Receptor (CAR) T-Cell Therapy
- Description: CAR T-cell therapy involves modifying your immune T cells genetically to recognize and attack cancer cells.
- Medication: Idecabtagene vicleucel (Abecma), also known as ide-cel, is administered to patients who have undergone at least four prior treatments.
- Mechanism: Modified T cells are infused back into the patient, where they multiply and target cancer cells.
Interferon Therapy
- Role: Interferon, a hormone-like substance naturally released by bone marrow and certain white blood cells, can impede the growth of myeloma cells.
- Application: Used as a drug, interferon therapy is prescribed to patients in remission, indicating the absence of detectable myeloma signs.

E. Corticosteroids

Supportive Role: Drugs like dexamethasone or prednisone are often prescribed alongside other treatments like chemotherapy to enhance their efficacy and manage side effects.

2. Emerging CAR T-Cell Therapy

Potential: While not yet approved for multiple myeloma, CAR T-cell therapy is under investigation for its safety and effectiveness.
Process: This therapy involves extracting T cells from the patient’s blood, genetically modifying them to target cancer cells using a disarmed virus, and reintroducing them into the body to multiply and attack cancer cells.

3. Stem Cell Transplant

Stem cell transplant is a treatment option your doctor might recommend for multiple myeloma management:

Procedure Overview

Stem Cell Collection: Your stem cells are harvested using a machine, or they may be sourced from a donor. These cells are then frozen and stored.
High-Dose Chemotherapy: You undergo intensive chemotherapy, sometimes coupled with radiation therapy. This aims to eradicate both diseased and healthy cells in your bone marrow.
Stem Cell Infusion: The stored or donated stem cells are reintroduced into your bloodstream via a catheter. These cells replace the destroyed bone marrow and initiate the production of healthy blood cells. It may take several weeks for your blood cell counts to normalize.

Considerations

Effectiveness: Stem cell transplantation can prolong survival in multiple myeloma patients.
Limitations: While it doesn’t cure the disease, it carries the risk of serious complications, such as increased susceptibility to infections.

4. Management of Bone Symptoms

In cases where multiple myeloma causes painful bone damage, your doctor may recommend additional treatments:

Bisphosphonates

Action: These drugs help slow bone breakdown and can be administered orally or intravenously.
Examples: Pamidronate (Aredia) and zoledronic acid (Zometa).
Precautions: Proper dental hygiene is crucial due to the rare risk of jaw damage associated with bisphosphonate use.

Monoclonal Antibodies

Medication: Denosumab (Prolia, Xgeva) can halt or even prevent the breakdown of bone cells.

Radiation Therapy

Procedure: Directed beams from a machine target affected bones or body parts, eliminating cancer cells and alleviating pain while strengthening weakened bones.

Home Care Tips

Managing multiple myeloma at home involves:

Healthy Diet: Maintaining a balanced diet to support overall health.
Regular Exercise: Helps to manage fatigue and improve strength.
Pain Management: Using prescribed medications or alternative therapies like acupuncture.
Hydration: Drinking plenty of fluids to help with kidney function.
Infection Prevention: Practicing good hygiene and avoiding sick people.

Prevention

While there is no sure way to prevent multiple myeloma, reducing risk factors can be beneficial:

Avoiding Exposure to Harmful Chemicals and Radiation: Particularly in occupational settings.
Maintaining a Healthy Weight: Through diet and exercise.
Regular Check-ups: Especially if there is a family history of blood cancers.

When to See a Doctor

Consult a healthcare professional if you experience persistent bone pain, frequent infections, unexplained weight loss, or other symptoms associated with multiple myeloma. Early diagnosis and treatment can significantly improve outcomes.

Outlook/Prognosis

Some people live many years with minimal symptoms, while others may experience a rapid progression of the disease.

Predicting Survival Rates:

Blood tests measuring levels of albumin and beta-2-microglobulin are commonly used to predict outcomes.
- Higher albumin levels and lower beta-2-microglobulin levels are associated with a better prognosis.
Additional lab tests or DNA analyses of plasma cells can provide more detailed information.

Sources

American Cancer Society. “Multiple Myeloma.”
Mayo Clinic. “Multiple Myeloma.”
National Cancer Institute. “Multiple Myeloma Treatment (PDQ®)–Patient Version.”
Leukemia & Lymphoma Society. “Myeloma.”
Genetic and Rare Diseases Information Center: “Multiple myeloma.”
Merck Manual Consumer Version: “Multiple Myeloma.”
Multiple Myeloma Research Foundation: “About Multiple Myeloma.”
Stem Cell Investigation: “The past, present, and future of CRM1/XPO1 inhibitors.”
FDA.
Abeloff, M. Abeloff’s Clinical Oncology, 4th edition, Churchill Livingstone, 2008.
Memorial Sloan Kettering Cancer Center: “Multiple Myeloma Diagnosis & Staging,” “Stem Cell Transplant for Multiple Myeloma.”
American Society of Clinical Oncology: “Multiple Myeloma: Treatment Options,” “Multiple Myeloma.”
Cancer Research UK: “How bisphosphonates work.”
UpToDate: “Overview of the management of multiple myeloma,” “Patient Education: Multiple Myeloma treatment (Beyond the Basics).”