Multiple myeloma

During the initial stages of multiple myeloma, the symptoms may not be noticeable and can vary depending on the individual. However, as the disease progresses, most people experience some commonly observed symptoms. The common symptoms are generally referred to by the acronym CRAB, which stands for:

• C: Elevated calcium levels
• R: Renal failure
• A: Anemia
• B: Bone damage

Other commonly observed signs and symptoms of multiple myeloma include:

• Nausea
• Bone pain, especially in the spine or chest
• Constipation
• Mental fogginess or confusion
• Loss of appetite
• Tiredness
• Frequent infections
• Weakness or numbness in the legs
• Excessive thirst
• Problems with urination
• Vision loss or vision problems
• Weight loss

In this type of cancer, abnormal plasma cells develop in the bone marrow and reproduce quickly. The rapid reproduction of cancerous myeloma cells overtakes the production of healthy cells in the bone marrow, leading to the disease. The exact cause of multiple myeloma is not known. However, frequent alterations and mutations of genes, especially chromosome 14, are commonly found in multiple myeloma. In addition, other mutated genes like c-Myc, NRAS, KRAS, and BRAF may participate in plasma cell proliferation.

The cancerous plasma cells continue trying to produce antibodies, as healthy plasma cells do, but these cells produce abnormal antibodies (monoclonal proteins, or M proteins) that do not function as normal antibodies. These abnormal antibodies build up in the body and cause complications such as:

• Kidney damage
• Increased risk of bone disorders

The exact cause for multiple myeloma is difficult to determine; however, researchers believe that certain factors increase the risk of developing the disease.

• Increasing Age: As one ages, the risk of developing multiple myeloma increases. Most individuals are diagnosed with the disease in their mid-60s. More than 75% of cases are reported in the age group of 55-85 years.
• Gender: Multiple myeloma is approximately 1.5 times more common among men than women globally. Suggested underlying factors include differences in health-risk behaviors such as smoking, alcohol consumption, and higher rates of obesity among men.
• Ethnicity: According to medical literature, individuals of the black race are more likely to develop multiple myeloma compared to other races.
• Environmental Factors: Exposure to chemicals such as benzene, insecticides, herbicides, hair dyes, organic solvents, and radiation has been found to increase the risk of developing multiple myeloma.
• Family History: Inherited variations in certain genes may contribute to the development of multiple myeloma in some individuals. Consequently, close relatives of people with multiple myeloma may have an increased risk of developing the disease.
• Personal History of Monoclonal Gammopathy of Unknown or Undetermined Significance (MGUS): MGUS is a benign proliferation of plasma cells that results in the production of monoclonal antibodies in high amounts (though not as high as seen with multiple myeloma). MGUS is a significant risk factor for the development of multiple myeloma, with about 19% of MGUS patients developing multiple myeloma within 2 to 19 years after diagnosis.
• Inflammatory Diseases: Inflammatory diseases such as type 2 diabetes, heart disease, and rheumatoid arthritis may increase the risk of multiple myeloma; however, this relationship is not well established.
• Other Factors: Additional factors contributing to disease occurrence include obesity, tobacco, and alcohol consumption, although these are not well established as risk factors for multiple myeloma.

A thorough clinical evaluation is required for the effective diagnosis of multiple myeloma. Based on the early signs and symptoms of the disease, your doctor will ask you to get a physical examination, followed by some laboratory tests, imaging tests, and if needed, a biopsy as well. Here are the tests that will be a part of a comprehensive diagnosis of multiple myeloma.

Physical examination

When you experience the early signs and symptoms, book an appointment with your physician at the earliest. Your doctor may ask you questions and enquire about your medical history. Based on the answers, he may suggest some of the following clinical tests to confirm the presence of the disease:

A. Blood tests

1. Complete blood count (CBC) CBC measures several components of the blood, including red blood cells, white blood cells, platelets, and others. The following levels are checked while studying the results of a CBC:
   • A decreased level of hemoglobin (anemia)
   • A decreased platelet count (thrombocytopenia) that can cause bleeding problems
   • A decreased level of white blood cells (granulocytopenia) which causes a weakened immune system.
2. Blood urea nitrogen (BUN) Urea nitrogen is the waste product formed by the body after consumption of food. The liver breaks down the protein in the food and produces urea nitrogen, which is released into the blood and eventually ends up in the kidneys. When the kidneys are healthy, they effectively remove the blood urea nitrogen; however, unhealthy kidneys are unable to do so and leave more of it in the blood. Therefore, the BUN test helps to see how much of the waste product remains in the blood and helps to detect the health of the kidneys. Laboratory-based blood chemistry tests will help to check for the levels of blood creatinine, albumin, calcium, and other electrolytes.
3. Creatinine laboratory test The creatinine test helps to measure how efficiently the kidneys are able to remove waste from blood. Creatinine is a natural waste product present in the blood and urine. Kidneys remove creatinine from the body by filtering it from the blood and then releasing it into the urine. This test measures the amount of creatinine in the blood. High creatinine levels mean that the kidneys are not functioning well and are common in people with myeloma.
4. Albumin test Albumin is a protein produced by the liver, and its function is to carry nutrients and prevent body fluids from leaking into the body. A serum albumin test checks the amount of albumin in the body. Any abnormality in the level of albumin indicates a likelihood of liver disease, kidney disease, or nutritional deficiency. Low levels can be seen in myeloma.
5. Calcium test Calcium is a mineral found in the body responsible for many vital functions like maintaining bone strength, muscle function, nerve function, and blood clotting. Abnormal levels of calcium can lead to several complications in the body, such as kidney disease, bone disease, and multiple organ tumors. Calcium levels may be high in people with advanced myeloma and cause symptoms of fatigue, weakness, and confusion.
6. Lactate dehydrogenase test Serum lactate dehydrogenase (LDH) test measures the levels of the enzyme lactate dehydrogenase in the blood. This enzyme is primarily involved in energy production and is found in nearly all of the body’s cells, with the highest levels in the cells of the heart, liver, muscles, and kidneys. It is released into the bloodstream as a result of tissue damage following an injury. A blood test to measure LDH levels can be a useful indicator of a patient’s prognosis, as high levels can indicate cancer recurrence.
7. Quantitative immunoglobulins This test helps to measure the levels of different immunoglobulins present in the blood, such as IgA, IgD, IgE, IgG, and IgM. The quantitative analysis of these immunoglobulins helps to determine if they are abnormal, suggesting the presence of disease or infection. In multiple myeloma, their levels usually differ from the normal ranges.

B. Urine test

Urine tests can be used to:

• Measure the amount of protein in the urine
• Assess the presence of free light chains
• Test for creatinine, a waste product excreted by the kidneys
• Check for the presence of bilirubin, a breakdown product of hemoglobin

You might most likely be asked to give a sample of urine that has been collected over a 24-hour period, so it can measure how much myeloma protein is present. Urine protein electrophoresis (UPE or UPEP) and urine immunofixation may be done to look for free light chains in the urine and to assess kidney function.

C. Bone marrow studies and biopsy

It is a medical procedure used as a diagnostic method in which a piece of tissue or a sample of cells is removed from the body and tested in a laboratory. Multiple myeloma is characterized by an increased number of plasma cells in the bone marrow, and therefore a bone marrow biopsy can help. It can be done at the doctor’s office or at the hospital.

1. Bone marrow aspiration Bone marrow aspiration can be performed by numbing the back of the pelvic bone with local anesthesia. A needle is inserted into the bone, and a syringe is used to remove a small amount of the liquid bone marrow. The bone marrow tissue is examined to check for the appearance, size, arrangement, and shape of the cells and to determine the presence of myeloma cells in the bone marrow. The liquid part of the bone marrow called the aspirate can also be sent for other tests such as immunohistochemistry, flow cytometry, and chromosome analyses, including karyotype and fluorescent in situ hybridization (FISH).
2. Immunohistochemistry It is a laboratory method that uses antibodies to check for the presence of certain antigens (markers) in the tissue sample. The sample is treated with special proteins that cause a color change and help to identify myeloma cells.
3. Flow cytometry It is a technology that helps to analyze single cells or particles as they flow past multiple lasers while being suspended in a buffered salt-based solution. The sample cells are treated with special proteins that stick only to certain cells, helping to identify if the cells are abnormal or cancerous.

D. Imaging tests

Along with the other chemical analyses and physical examination, the doctor may also recommend you to get a few imaging tests done. It will help provide a clear visual of the concerned or affected organ or tissue.

1. X-ray scan Multiple myeloma can cause tissue damage at the site of disease initiation. An X-ray produces images of the organs and confirms the presence of any tissue damage. It can be done to see if there is a suspicious area that might be cancerous or to understand the spread of the cancer.
2. Magnetic resonance imaging (MRI) It is an imaging test that uses a magnetic field to take pictures of organs and structures inside the human body. An MRI can help understand the initiation and spread of the disease.
3. CT scan A CT scan, also known as computed tomography, is a machine that takes a series of X-rays to make a picture with minute details. The scan helps to image bones, blood vessels, and soft tissues from different angles. It can also be used to guide a biopsy needle into an area of concern.

If your doctor diagnoses you with multiple myeloma, the doctor will then use the information gathered to classify the disease into the respective stages: stage I, II, III, or IV.

As known, there aren't vaccines available for all the different cancers reported. There is no known way to prevent multiple myeloma. Scientists are still investigating if treating certain high-risk factors, such as smoldering multiple myeloma, could help keep it from becoming active multiple myeloma.

It is best advised to practice a healthy lifestyle, including:

• Healthy eating habits
• Avoiding smoking
• Limiting excessive alcohol consumption

These practices may help minimize the chances of developing any form of cancer.

There are different treatment options available for multiple myeloma depending on the severity of the disease. The options can help ease the pain, reduce complications, and slow the progression of the disease. Common treatment options include:

• Chemotherapy
  Chemotherapy medicines are the mainstay of treatment used to kill cancer cells. It is an aggressive form of drug therapy that helps to kill fast-growing myeloma cells. In chemotherapy cycles, a certain number of days of treatment are followed by days of rest to allow the body to recover. Often, a combination of chemotherapy agents is used to treat cancer. Commonly used chemotherapeutics are:
• Vincristine
• Daunorubicin
• Cytarabine
• Mercaptopurine
• Ifosfamide
• Radiation therapy
  As the name suggests, radiation therapy uses radiation (high-energy rays similar to X-rays) to kill the cancer cells. The strong beams of energy kill the myeloma cells quickly in specific sites. This therapy can also be used along with other treatment modalities such as chemotherapy and surgery.
• Targeted therapy
  Targeted therapy medications help to block a chemical in the myeloma cells that destroys the protein and causes the cells to die. These drugs are given against a cancer cell-specific target, which is generally not present in normal dividing cells of the body, thereby minimizing the adverse effects of the drug treatment. These therapies are generally expensive but more specific in their action. Examples of targeted therapy include:
• Bortezomib
• Carfilzomib
• Immunotherapy
  This therapy is considered a game changer in cancer treatment. Immunotherapy uses your immune system to fight cancer. Your body's disease-fighting immune system may not attack your cancer because the cancer cells produce proteins that help them hide from immune system cells. Immunotherapy works by interfering with that process. Commonly used immunotherapeutics are:
• Belantamab is an antibody-drug conjugate that targets the BCMA pathway and is approved for subsets of patients with advanced multiple myeloma.
• Daratumumab is a monoclonal antibody that targets the CD38 pathway and is approved for subsets of patients with advanced multiple myeloma.
• Elotuzumab is a monoclonal antibody that targets the SLAMF7 pathway and is approved for subsets of patients with advanced multiple myeloma.
• Isatuximab is a monoclonal antibody that targets the CD38 pathway and is approved for subsets of patients with advanced multiple myeloma.

In addition to the FDA-approved therapies, there are some second-generation monoclonal antibodies targeting the CD38 and other targets, CAR-T cells, and natural killer cells that are being investigated in clinical trials as well.

• Corticosteroids
  These medications help to regulate the immune system and control inflammation. This steroidal therapy has been found to be effective against multiple myeloma as well.
• Bone marrow transplant
  Also known as stem cell transplant, it is a special type of therapy for patients with certain cancer types such as multiple myeloma. Through this process, the unhealthy bone marrow cells are treated to kill the abnormal cells, and the healthy cells are filtered and transfused back into the patient. Bone marrow transplants have been successfully used to treat cancers, immune deficiency disorders, and solid tumor cancers since the 1960s. Prior to being considered a candidate for a bone marrow transplant, doctors will evaluate if you are a good candidate. You may be advised to undergo some initial therapy which may include targeted therapy, immunotherapy, corticosteroids, and even chemotherapy. Depending on the stage of the disease, age, and overall health, a combination of different treatment options is often considered as well.

Patients with multiple myeloma may feel fatigued and are at an increased risk of frequent infections. Additionally, the treatment regimen for multiple myeloma can be exhaustive and stressful. For instance, chemotherapy is often associated with several side effects. Here are a few things to keep in mind while taking care of yourself or a loved one suffering from multiple myeloma:

• Follow good hand hygiene.
• Avoid crowded places.
• Make a conscious effort to keep infections away.

• Eat fresh home-cooked meals and drink plenty of water or energy drinks daily.

• Eat small and frequent meals throughout the day.

• Embrace the side effects of chemotherapy such as hair loss and skin discoloration. Counseling and connecting with others who are going through the same can aid in acceptance.

• Nausea and vomiting due to chemotherapy can be managed with medications or home remedies like sucking on peppermint lozenges.

• Meditation is an effective way to practice relaxation. Try to incorporate it into your daily routine.

• Engage in some form of physical activity such as yoga or evening walks. This can help boost energy levels and alleviate symptoms of chronic fatigue.

Meditation is a simple and effective way to maintain your mental and physical well-being. Here are the benefits of meditation.

Multiple myeloma can lead to several complications depending on the severity or stage of the disease and the effect of the treatment regimen being undertaken. Common complications include:

• Bone Disorders: Multiple myeloma affects the bones, usually the back, hips, and ribs. It often presents as a frequent dull pain that can worsen with movement. The disease can also cause thinning and weakening of bones, leading to frequent fractures, particularly in the spine and long bones (arms and legs).
• Blood-Related Problems: A significant portion of the Indian population with myeloma has been found to have anemia. Anemia is a condition characterized by a deficiency of healthy red blood cells, which impairs the ability to carry adequate oxygen to the body’s tissues. This condition can cause fatigue and weakness. Multiple myeloma affects blood cell production in the bone marrow, contributing to anemia.
• Frequent Infections: Myeloma cells, like other cancer cells, inhibit the body’s ability to fight infections. The disease weakens the immune system, making the patient more susceptible to frequent infections.
• Kidney Damage: Multiple myeloma adversely affects kidney function. In severe cases, there is a risk of kidney damage or failure if left unaddressed or untreated. Common signs of kidney impairment include weight loss, poor appetite, itchy skin, recurrent and continuous hiccups, tiredness, and lack of energy.
• Chronic Pain: Patients with multiple myeloma may experience chronic pain due to various reasons, including bone lesions, neuropathy, bone marrow examinations, or pain related to medications.
• Hypercalcemia: Elevated levels of calcium in the blood can occur due to excessive calcium release from affected bones in individuals with multiple myeloma. Common symptoms of hypercalcemia include extreme thirst, stomach pain, constipation, confusion, and drowsiness.

There aren't any alternative therapies known to treat multiple myeloma as such; however, they may help cope with the stress, treatment regimen, and side effects of the disease. Some alternative therapies that may assist in coping with multiple myeloma while undergoing treatment include:

• Yoga: Yoga helps to lower fatigue, reduce stress, improve muscle tension, and enhance physical functioning for cancer patients. In the case of multiple myeloma, strength is considered more important compared to cardio activity. Therefore, yoga could serve as an additional mode of physical activity that supports your fight against the disease. Here are some of the health benefits of yoga.
• Music Therapy: Though there is no evidence to support that music therapy helps to treat cancer, it has been found to be a beneficial psychological therapy for many cancer patients. Music has been shown to relieve nausea and vomiting caused by chemotherapy and other anti-cancer medications.
• Exercise: According to a 2013 study published in BMC Cancer, prescribed exercise programs for multiple myeloma patients are acceptable and safe. Undergoing treatment generally leads to a loss of lean muscle mass; therefore, it is advisable to build lean mass and develop more metabolically active muscle mass during the recovery phase. You may require guidance and appropriate input from physical therapists.
• Massage Therapy: Massage is considered a relaxation technique and an effective treatment for muscles and soft tissues, which is often needed for patients undergoing cancer treatment. It is a popular complementary therapy used by people living with cancer. Massage therapy helps to ease muscle tension, lower stress, and release trigger points.
• Diet: A healthy diet is essential for good health and nutrition. Include fresh fruits, vegetables, herbs, and spices in your daily diet to help boost your energy levels. Stay hydrated by including fluids such as fresh fruit juices and water. Preference should be given to home-cooked food while avoiding raw, uncooked, and packaged food. A healthy diet is key to maintaining energy levels and fighting infections when unwell.
• Aromatherapy: Aromatherapy is a popular complementary treatment for cancer patients, defined as the use of essential oils from plants (trees, flowers, or herbs) to improve physical, mental, and spiritual well-being. Research suggests that aromatherapy helps relieve anxiety, nausea, and vomiting in cancer patients.
• Acupressure and Acupuncture: Acupressure and acupuncture techniques help combat pain, fatigue, and other symptoms. Studies suggest that these techniques can reduce the need for opioids in managing cancer pain.

Advancements in science and technology have led to better chances of survival for patients with multiple myeloma. The fight against cancer can impact the emotional health of both the patient and their families; however, it is worth the struggle if the patient manages to persevere. Here are a few tips that can be helpful for patients with multiple myeloma:

• Join a support group: Staying positive during cancer treatment can be much easier with the encouragement of others. A support group can keep you motivated, as participants share their insights into cancer treatment.
• Surround yourself with positive people: When you’re feeling low, friends or family members can provide essential encouragement. Additionally, a trained mental health counselor can be invaluable during distressing times.
• Learn and accept the diagnosis: Don’t hesitate to ask your healthcare team about anything you don’t understand. It’s best to discuss your health and condition with your doctor.
• Get rest: When you’re feeling anxious, depressed, or exhausted from treatment, prioritize sleep. Lack of rest can exacerbate feelings of anxiety or despair. You’re more likely to feel positive if you’re well-rested.