Multiple Myeloma

Multiple Myeloma 101 

A relatively rare type of blood cancer, multiple myeloma cases consist of the 0.76 percent of all cancer cases in the United States. It usually does not present symptoms and is diagnosed in the advanced stages. In this piece, we will go over the basics of multiple myeloma. 

What Is Myeloma? 

Myeloma is a type of blood cancer that occurs in a specific type of white blood cells called plasma cells, also called plasmacyte. Plasma cells’ role is to help fight infections by producing antibodies that are able to recognize and attack germs. The special antibodies have various names such as monoclonal immunoglobulin, monoclonal protein (M-protein), M-spike, or paraprotein]. Myeloma defines the situation where the plasma cells become cancerous. When myeloma occurs, the plasma cells start reproducing quickly, producing antibodies that are unable to help the immune system and accumulate in the bone marrow. The myeloma does not present itself with an observable physical presence such as a lump, but rather damages the bone marrow and affects the production of healthy blood cells. The accumulation of cancerous plasma cells forces other types of healthy blood cells to decrease in number, which eventually causes a weakened immune system. 

Myeloma has two main types: asymptomatic (smoldering) and symptomatic. In asymptomatic myeloma, no symptoms or tissue damage are observed. And in symptomatic myeloma, both symptoms and tissue damage are present. 

Although it is not clear why myeloma develops in the body, scientists found links connecting a surplus of protein molecules named immunoglobins to the disease. This condition in blood is called monoclonal gammopathy of unknown significance (MGUS). Although MGUS does not cause symptoms alone, it presents a risk of developing multiple myeloma with a percentage of about 1 in every 100 MGUS patients. 

What Is Multiple Myeloma? 

Myeloma is usually called multiple myeloma because the accumulation of cancerous plasma cells occurs in multiple parts of the body containing the bone marrow, such as the brain, spine, pelvis, etc. Similar to myeloma, multiple myeloma  causes a decrease in healthy blood cells, damage to the nearby bone tissue and organs, as well as circulatory problems. Low blood counts, bone and calcium problems, increase in infections, and kidney problems are common symptoms in multiple myeloma patients. 

Multiple myeloma is not considered a single disease, there are many subtypes that are either inactive or active. Active multiple myelomas are labeled as aggressive or non-aggressive based on the rate of growth and the spread of the cancer, as well as the symptoms and complications associated with the subtype. Myeloma subtypes are considered active if symptoms or organ damage from the disease have occurred. 

Multiple myeloma is the most common type of plasma cell cancer. More and more studies suggest that multiple myeloma runs in family. As of 2022, the disease is not yet curable but treatable. However, the clinical trials focusing on multiple myeloma provide new standards for patients every year and give them a chance to lead a life with higher quality. The overall five-year survival rate for multiple myeloma patients is 55 percent in the United States.  

What Is the Difference Between Myeloma and Multiple Myeloma? 

There is actually no difference between myeloma and multiple myeloma. The difference in naming is derived from the number of locations the disease is seen in the body. Multiple myeloma starts in the bone marrow, which is the spongy tissue in the bones where blood cells (red & white blood cells and platelets) are produced. And since the bone is a structural element of the body, malignant tumors usually appear in multiple locations, multiple myeloma is more commonly used. 

Sources: 

cancer.org 

Bloodcancer.org.uk 

mayoclinic.org 

cancer.net  

Multiple Myeloma Symptoms and Signs 

Symptoms and signs are what lead us to the path of diagnosis of a disease. A symptom is a change or a condition in the body that the patient experiences, such as pain, nausea, or fatigue. It is subjective in nature. A sign on the other hand is an objective change or condition in the body such as fever, blood pressure, or heart rate but observed, evaluated, or measured by a person other than the patient. In this piece, we will go over the common symptoms and signs that multiple myeloma patients experience. 

What Are the Symptoms of Multiple Myeloma? 

Although some types of multiple myeloma are asymptomatic, some are symptomatic. Most patients do not present any signs or symptoms in the early stages, which leads to a late diagnosis of the disease. So how is it possible to diagnose multiple myeloma in the early stages? It is usually discovered during a physical examination, or a urine or blood test intended for another reason. There are some common symptoms such as thirst, dehydration, frequent urinating, constipation, and confusion that many patients with other diseases experience as well. This is one of the reasons why many patients do not suspect multiple myeloma soon. In this part, we will go over some specific symptoms indicating the presence of multiple myeloma including various problems related to blood, bone, kidney, and nervous and immune system. 

Bone-related problems: One of the most common symptoms experienced by multiple myeloma patients is bone-related problems, we will briefly go over them. 

• Bone pain: Many patients visit the doctor with a complaint of pain in either their back, hips, or skull. 
• Weakness in bones: When myeloma is present, the regenerative process of the bones is interrupted; the cells (osteoclast and osteoblast) that help the bone stay strong and healthy are decreased. This eventually leads to bone weakness. When the patient suffers from multiple myeloma in the spine, their vertebrae become weak, get compressed and thus might lead to shortening height of the patient.  
• Broken bones: Broken or fractured bones are common in multiple myeloma patients. The reason for it is the accumulation of myeloma cells in the bone marrow and the cortical bone (the protective layer on the outer bone). The accumulation causes the bone to become thinner, which is called osteoporosis, the condition where the bones become easily breakable or fractured. The more fractured or broken the bones are, the higher the patient’s calcium levels increase. This leads to hypercalcemia, which causes various side effects such as kidney damage, constipation, and drowsiness. 

Blood-related problems: When myeloma causes the plasma cells to overgrow and leave no room for other blood cells, this leads to various blood-related problems. 

• Anemia: The lack of or decreased levels of red blood cells in the body is called anemia, which causes the patient to experience weakness and fatigue. 
• Thrombocytopenia: This means the lack or decreased level of platelets in the body, and results in easy bleeding (such as in the nose or gums) and bruising. 
• Leukopenia: It refers to the lack or decreased level of white blood cells in the body, which causes a lowered defense against infections. 
• Hyperviscosity: Refers to the condition where the blood is so thickened that it affects the circulation in the whole body. It causes problems such as cloudy vision. 

Neurological problems: These problems might have various causes such as uremia, hyperviscosity, or hypercalcemia. In addition to these metabolic conditions, some patients experience neurological complications caused by cranial nerve infiltration, spinal cord compressions or peripheral neuropathy. 

Kidney damage: The abnormal and uncontrolled increase in the calcium level in the body is called hypercalcemia, which is the main reason for kidney damage in multiple myeloma patients. 

Weight loss: This is generally a common result of various symptoms multiple myeloma patients are experiencing such as hypercalcemia, kidney damage, or abnormal changes in the blood. Hypercalcemia generally causes loss of appetite, which leads to weight loss. 

Fatigue: Fatigue is generally a result of the anemia experienced by the patient. Sometimes, other cellular problems such as the overproduction of cytokine might be the reason for fatigue in multiple myeloma patients. 

Sources: 

cancer.net 

mayoclinic.org 

emre.who.int 

Multiple Myeloma Statistics 

Multiple myeloma makes up about 1.8 percent of all new cancer cases in the United States, which classifies the disease as a rare one. According to the American Cancer Society, only 1 in every 132 cancer patients is suffering from multiple myeloma, which accounts for 0.76 percent. In 2022 the National Cancer Institute expects to see 34,470 new cases of multiple myeloma and 12,640 deaths due to this disease. These deaths correspond to about 2.1 percent of estimated deaths caused by cancer. Multiple myeloma is not as common as the other blood cancers such as lymphoma and leukemia. The number of patients diagnosed with multiple myeloma all over the world is just over 176,000. 

People with a history of monoclonal gammopathy of undetermined significance (MGUS) are at greater risk of developing multiple myeloma. Males in general (disregarding the ethnicity) have multiple myeloma more than females with a rate of 8.8 percent in males to 5.9 percent? in females.
 

Multiple Myeloma in Numbers 

Although multiple myeloma is a rare disease the statistics about the disease are improving over the years thanks to the clinical trials and people who enroll in them. Here, we will go over the numbers regarding multiple myeloma patients in the US and around the world. 

The median age of diagnosis: According to the data provided by the National Cancer Institute, the median age of diagnosis for multiple myeloma is 69 years old. And it is generally diagnosed between people at the age of 65 and 74. 75-84 is the second most common age group the disease is diagnosed at, followed by the group between 55-64. 

The median age of death: According to the data provided by the National Cancer Institute, the median age of death due to multiple myeloma is 75 years old. The second age group with the highest death rates is 65-74. The third is over 84 years old. According to the data gathered between 2015-20109, the death rate anticipated is 3.2 percent for male patients.  

The lifetime risk of developing the disease: Multiple myeloma is more common among non-Hispanic, Black individuals than in any other individual from other ethnic origins. Based on the data gathered between 2017-2019, about 0.8 percent of the general population will be diagnosed with multiple myeloma. Data regarding the percentage of data on the development of the disease the death rates are diminishing due to the number of clinical trials carried out not only in the US but all over the world. 

Multiple Myeloma Survival Rates 

The presence of a single plasmacytoma and multiple myeloma is important in determining the survival of multiple myeloma. While the single plasmacytoma has a 78 percent five-year survival rate, the multiple myeloma has a 55 percent survival rate. Thanks to the clinical trials, scientists can determine the factors based on genetics and metabolism that increase the survival rate of patients. The earlier the disease is diagnosed, the greater the chance of survival. 

The survival rates change based on the stages of multiple myeloma. 4 percent of the cases diagnosed are localized, while 95 percent of the cases are metastasized. In localized cases, the survival rate is about 78.5 percent, while the same rate is 57 percent, or metastasized patients. For the 4 percent diagnosed at the early stages, the survival rate is about 77 percent, compared 54 percent if diagnosed at later stages. 

The clinical trials focusing on multiple myeloma are increasing the rate of survival as well as the quality of life for patients suffering from the disease. Please click to explore your options to find a suitable clinical trial for your multiple myeloma. 

Sources: 

cancer.gov 

cancer.org 

Living with and Managing Multiple Myeloma 

After a diagnosis of multiple myeloma, it’s normal to reflect on how you can best take care of yourself. 

Most importantly, meeting your health care team on a regular basis to monitor your progress and make treatment decisions is a critical part of staying well. 

Taking care of yourself, on the other hand, goes beyond doctor’s visits and treatments. Taking additional actions can improve your quality of life and sense of well-being. 

Here are some suggestions for regaining control of your life and health. 

Coping With Treatment 

Those who have undergone cancer treatment characterize the initial months as a period of transition. It’s less about “getting back to normal” and more about figuring out what is normal for you right now. People frequently state that life has taken on new significance for them or that they have a new perspective on things. It’s possible that your new normal will include: 

• Changes in the way you eat and the things you do 
• New or different sources of financial, social, or emotional support 
• Needing help doing things you used to do without problems 
• Permanent scars on your body 
• Emotional scars from going through so much 

You may have a new perspective on yourself, or others may have a new perspective on you. Allow yourself time to adjust to your new normal, whatever it is. Take each day as it comes. 

Coping With Physical Side Effects 

Physical side effects from cancer are often difficult to avoid. Most cancer patients endure some type of unfavorable physical reaction to the disease, or the medications used to treat it, whether it’s scar tissue from surgery or hair loss from chemotherapy. 

Aiding patients in managing and reducing side effects can help them avoid treatment delays or interruptions while also increasing their quality of life. Still, some patients are concerned that treating side effects would entail adding another pill to their daily regimen. Medication, on the other hand, isn’t always required. In truth, simple lifestyle modifications such as following a specified diet or including light exercise in one’s daily routine can make a major difference. 

Coping With Emotional and Social Effects  

People deal with intense emotions in a variety of ways. You might want to experiment with some of these coping tactics to determine what works best for you. 

Recognize and be honest about your feelings: Make an attempt to describe or discuss them. Because you want to protect your family and friends, it may be difficult to tell them how you really feel. Being honest, on the other hand, can help you improve communication and strengthen your bonds with individuals you care about. 

Talk to someone: Finding the courage to speak with just one person can be a huge step toward feeling better. A friend, a relative, or a mental health professional could be the person who helps you. It may also be beneficial to speak with someone who has gone through a similar cancer experience. 

Talk to your healthcare team: Let them know how you’re feeling and if you’re having trouble dealing with the situation. They can assist you in locating resources that can assist you in coping. Pose inquiries. If you don’t understand something your healthcare staff is saying, or if you need more information or assistance, tell them. 

Learn about multiple myeloma and its treatment: Some people think that gathering information and applying it to make decisions gives them a sense of control. Others choose not to know too much and don’t want to be involved in their care decisions. Tell your healthcare staff how much information you require. 

Be as physically active as possible: Exercise helps improve your mood, your sleep and your appetite. 

Eat well:  Eating a variety of foods and well-balanced meals can help you feel better and stay stronger. 

Keep your life as normal as possible: Even though a cancer diagnosis can cause a lot of changes in your life, try to maintain as much of your normal routine and habits as possible. Every day, get up and dress. Maintain a busy social life. 

Caring for a Loved One With Cancer 

Caring for a cancer patient is a crucial duty that contributes significantly to the patient’s recovery. Being a caregiver has its own set of difficulties. The majority of people are unprepared for this role. Adjusting to the changes requires time and patience. 

Educate yourself: Learn everything you can about your loved one’s cancer, treatment options, and any side effects. Inquire with your loved one’s physician about patient education materials and other helpful resources. The more you and your loved one understand about the disease and what to expect, the more confident you and your loved one will be in treatment selections. 

Find a cancer team you trust: Find doctors who are familiar with your loved one’s type of cancer and who work together to give tailored treatment. It’s also crucial to use an integrative strategy to help your loved one handle adverse effects during therapy. Additionally, having all of your loved one’s doctors in the same place allows for more convenience and streamlined care. 

Stay organized: Keeping track of your loved one’s medical history, test results, and prescriptions is a good idea. Make a list of appointments, doctor‘s’ names, and contact information, including the pharmacy’s phone number. Making a list of your daily responsibilities and prioritizing what has to be done is also beneficial. 

Keep your loved one’s doctors informed. Changes in sleep, mood, bowel habits, or hunger, for example, should be reported to your loved one’s doctor. These adverse effects could cause your loved one’s treatment to be disrupted, lowering his or her quality of life. Don’t put off contacting your loved one’s doctors until the next scheduled checkup. 

Follow your loved one’s lead. Telling your loved one what to think, feel, or do is not a good idea. Allow your loved one to take the lead because you have no idea what he or she is going through right now. Try stating, “I love you, and we’ll get through this together,” instead of “I understand how you feel.” 

Accept your loved one’s bad days. Your loved one may be unhappy, angry, or simply having a poor day at times. Expecting your loved one to “remain optimistic” all of the time is impractical. Moreover, placing these obligations on him or her would only increase his or her frustration, guilt, and stress levels. Accept difficult days, give your loved one space if necessary, and don’t take things personally. 

Take a break from cancer. It doesn’t have to be about cancer all of the time. Every now and then, you and your loved one may require a respite from cancer. If your loved one doesn’t want to talk about it, don’t bring it up. Instead, concentrate on other things, such as spending time with your family doing something enjoyable. 

Watching for Recurrence 

When your treatment is ended, you’ll probably be relieved to be free of it so you can return to your old routine. You may be sad and worried at the same moment. It’s natural to wonder if the cancer may return and what will happen next. 

The most prevalent emotional problem people confront following cancer is the fear of it returning. 

When cancer returns after you’ve finished therapy and it hasn’t been identified in your body for a while, it’s called a recurrence. If there have been no signs of cancer for a year or more, doctors usually call it a recurrence. Cancer may reappear in the same spot where it first appeared, or it may occur elsewhere in the body. 

You may have questions about the possibility of recurrence, such as: 

• Will there ever be a time when I’ll be sure my cancer won’t come back? 
• What should I look for if I am worried about a recurrence? 
• What symptoms should I report to my health care team that might mean the cancer is back? 
• What can I do to lower the chance my cancer will come back? 
• What other health problems am I at risk for after my cancer treatment? 

It’s natural to be concerned about the cancer returning, especially in the first year following therapy. Survivors may worry that any new symptom indicates that the cancer has returned. Keeping a diary of symptoms to mention at your next follow-up appointment may be beneficial. Also, inquire about the next steps in your cancer treatment. 

Also, while many people claim that their fear of cancer returning decreases with time, factors like follow-up visits, anniversary events, or a family member’s illness can cause you to be concerned about your health. This is perfectly natural, and it’s an excellent opportunity to get help. 

Sources: 

https://www.cancer.org 

https://cancer.ca 

https://www.cancercenter.com 

What are the Risk Factors of Multiple Myeloma? 

Anything that raises a person’s chances of acquiring cancer is referred to as a risk factor. Although risk factors have a role in the development of cancer, the majority of them do not cause cancer. Some people who have a number of risk factors never get cancer, whereas others who have none do. Knowing your risk factors and discussing them with your doctor, on the other hand, may help you make better lifestyle and health-care decisions. 

Multiple myeloma has no recognized or well-understood causes. There are currently no known preventative measures. There are currently no known high-risk factors for myeloma. 

Although the mutations that cause myeloma are acquired rather than inherited, a family history of the disease is a known risk factor. First-degree relatives of people with multiple myeloma have a 2 to 3 times higher risk of developing the disease. First-degree relatives are parents, siblings, and children. 

The following factors can raise a person’s risk of developing myeloma: 

Age 

Myeloma occurs most commonly in people over 60. The average age at diagnosis is 70. Only 2%percent of cases occur in people under 40.  

Race 

Myeloma occurs twice as frequently in bBlack people than in white people. The reasons why are unclear, although the disease appears to also be more common in the Middle East, North Africa, and the Mediterranean.  

Exposure to Radiation or Chemicals 

People who have been exposed to radiation or to asbestos, benzene, pesticides, and other chemicals used in rubber manufacturing may be at higher risk for developing myeloma. People often exposed to wood products, such as carpenters, furniture makers, and paper makers, are also at higher risk. There is also a high incidence of myeloma among professional firefighters and those exposed to herbicides, including Agent Orange.  

Family History 

People with a history of solitary plasmacytoma of the bone are at greater risk for developing multiple myeloma.  

Can Multiple Myeloma Be Prevented? 

With multiple myeloma, few cases are linked to risk factors that can be avoided. There is no known way to prevent multiple myeloma from developing in those people with monoclonal gammopathy of undetermined significance or solitary plasmacytomas. Research is investigating if treating certain high risk smoldering multiple myeloma may keep it from becoming active multiple myeloma. 

Sources: 

https://www.cancer.net 

https://www.cancer.org 

https://www.mayoclinic.org 

Diagnosis of Multiple Myeloma 

Multiple myeloma is diagnosed using a variety of tests, whereas, not every test will be used for every patient. When choosing a diagnostic test, your doctor may consider the following factors: 

• The type of cancer suspected 
• Your signs and symptoms 
• Your age and general health 
• The results of earlier medical tests 

The following are blood and urine tests used to diagnose multiple myeloma:  

M protein 

M protein, an antibody monoclonal immunoglobulin, is frequently secreted by myeloma cells. M protein levels in a patient’s blood and urine are used to assess the severity of the condition, as well as to track how effective treatment is working and whether the disease is developing or returning. Only the light chain of the antibody is secreted by certain myeloma cells in some patients. Serum protein electrophoresis (SPE or SPEP) or urine protein electrophoresis are used to determine the amount of M protein in the blood or urine (UPE or UPEP).  

Immunoglobulin 

Immunoglobulin levels are checked to see how much antibody is present in the blood. Immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M are the antibodies in question (IgM). When the cancer protein level rises in multiple myeloma, the normal antibody levels fall. 

Light Chains 

The amount of free light chains in the blood can be measured before the blood is filtered by the kidneys. This test is called a serum free light chain assay. This is a more sensitive test than measuring M protein in the urine, but both are important to measure. When a light chain is found in the urine, it is called the Bence Jones protein. 

This test also determines the light chain ratio, which is used to determine if one form of light chain is more prevalent than the other. Light chains are divided into two types: kappa and lambda. In normal circumstances, they are present in equal proportions in the blood, resulting in a 1 to 1 ratio. The ratio will be different if one form of light chain is more prevalent than the other, which could indicate myeloma. 

Lactase Dehydrogenase (LDH) 

LDH is an enzyme, which is a type of protein. It is in almost all tissues in the body. Damaged tissues release LDH into the bloodstream, so LDH is used as a sign that the body has been injured or a disease is present. In myeloma, LDH levels can be used to help determine prognosis, which is the chance of recovery, and the stage (see Stages).

Serum Albumin and Serum Beta-2 Microglobulin (β2-M) 

The levels of serum albumin and serum β2-M are measured using blood tests. Serum albumin is a blood protein made by the liver that is necessary for maintaining proper blood volume and general health. β2-M is a small protein that plays a role in the body’s immune response. 

Another protein produced by myeloma cells is this one. Although this protein does not create difficulties in and of itself, it can be used to predict a patient’s prognosis (outlook). High levels indicate that the disease has progressed, and the prognosis may be poor. 

Sources: 

https://www.cancer.net 

https://www.mayoclinic.org 

Multiple Myeloma Treatment Options 

Multiple myeloma is a type of cancer that occurs in the spongy bone marrow, which produces blood cells in the body. Because cancer often affects various parts of the body such as the spine, skull, pelvis, and ribs, it’s called multiple myeloma. Treatment options are shaped by whether the patient shows symptoms, the stage of the disease, or the person’s general health status. You can find various treatment options for multiple myeloma in this article. 

How Is Multiple Myeloma Treated? 

Treatment of multiple myeloma varies depending on the stages of the disease. A personalized treatment method is usually created by looking at the patient’s symptoms or general health. The treatment aims to alleviate pain, destroy myeloma cells, control tumor growth, and enable patients to lead active lives. Since multiple myeloma patients do not usually show symptoms, they do not need treatment and can be closely monitored by the doctor through checkups. This approach is called active surveillance or watchful waiting. It isThis type of the disease is also called smoldering multiple myeloma (SMM). Doctors monitor the course of the disease at regular intervals. Asymptomatic patients with multiple myeloma can live for many years without the need for treatment with good observation. 

Treatment Overview For Patients With Symptoms 

If symptoms occur in multiple myeloma, active treatment begins. Standard treatment methods such as targeted therapy, chemotherapy, immunotherapy, corticosteroids, bone marrow transplantation, and radiation therapy are applied by doctors, taking into account the stages of the disease into account, the previous treatment methods, if any, and the general health status of the person. 

Chemotherapy 

Chemotherapy (chemo) is the process of using drugs to destroy cancer cells by preventing cancer cells from growing, dividing, and making more cells. Medications can be taken orally and given through a vein or muscle. In chemotherapy treatment, a combination of different drugs is administered to patients. These drugs include cyclophosphamide, doxorubicin, melphalan, etoposide, cisplatin, carmustine, and bendamustine. The dose of chemotherapy to be given to patients varies depending on the stage of the disease. When the combination used does not respond positively, a different treatment method can be applied to the person. Patients given chemotherapy may experience side effects such as fatigue, risk of infection, nausea, vomiting, hair loss, loss of appetite and diarrhea or constipation, peripheral neuropathy (tingling or numbness in the feet or hands), blood clotting problems, and low blood counts. Side effects usually go away when treatment is finished. If the side effects cause an allergic reaction, such as a skin rash, the drug may need to be discontinued. 

Targeted Therapy 

While chemotherapy acts on all cells, targeted therapy only targets cancer-specific genes, proteins, or the tissue environment that contributes to cancer growth and survival. This prevents the growth and spread of cancer cells while preserving the healthy tissues in the body. It can also be used with other? targeted therapies, chemotherapy, immunomodulatory drugs, or steroids. 

Targeted therapies for multiple myeloma includes: 

• Proteasome inhibitors: Bortezomib (Velcade), carfilzomib (Kyprolis), and ixazomib (Ninlaro). These drugs can be used to treat newly diagnosed myeloma and recurrent myeloma. 
• Histone deacetylase inhibitors: Panobinostat (Farydak), an inhibitor of the histone deacetylase enzyme (HDAC), also treats recurrent myeloma. HDACs, help keep DNA tightly coiled, while panobinostat helps unfold DNA and activate genes that stop or slow the growth of cancer cells. 
• Monoclonal antibodies: Elotuzumab (Empliciti) and daratumumab (Darzalex). It binds to myeloma cells and tags them for removal by the person’s immune system. Daratumumab can be given to treat newly diagnosed multiple myeloma. 
• Nuclear export inhibitors: Selinexor (Xpovio) is a targeted therapy given in combination with dexamethasone, a steroid available as a generic medicine. This combination is used to treat adults with multiple myeloma that has come back after four or more previous treatments. It can also be given in combination with bortezomib and dexamethasone to people patients who have had at least one prior therapy. 
• B-cell maturation antigen (BCMA) targeting agent: Belantamab mafodotin-blmf (Blenrep) is an antibody-drug approved by the US Food and Drug Administration (FDA) to treat adults with recurrent or resistant multiple myeloma who have received at least four prior treatments. Thalidomide (Synovir, Thalomid), lenalidomide, and bortezomib can also be used effectively as maintenance therapy to prolong the response of the disease to initial therapy or after bone marrow/stem cell transplantation. Studies have shown that maintenance therapy with lenalidomide and/or bortezomib increases patients’ survival rate and prolongs the time they live without active myeloma. 

Immunomodulatory Drugs 

Immunomodulatory drugs are administered specifically to the targeted area or disease. It acts on the immune system by increasing the production of serum antibodies by increasing (immunostimulators) or decreasing (immunosuppressives). Thalidomide, lenalidomide (Revlimid), and pomalidomide (Pomalyst) are classified as immunomodulatory drugs that stimulate the immune system to treat myeloma and prevent blood vessels from forming myeloma cells and feeding these cells. The FDA approves thalidomide and lenalidomide to treat newly diagnosed patients. Lenalidomide and pomalidomide are also effective in the treatment of recurrent myeloma. 

Steroids 

Steroids are very effective in temporarily reducing the load on plasma cells. They suppress the immune system and affect the entire immune system. They are usually taken orally as tablets. It can be used alone or combined with other drug therapiesy such as targeted therapy or chemotherapy. Myeloma treatment uses corticosteroid drugs that regulate the immune system and are active against myeloma cells to control inflammation in the body. Corticosteroids help destroy myeloma cells and reduce nausea and vomiting caused by chemotherapy. The most common types used to treat myeloma are dexamethasone and prednisolone. When corticosteroids are used for a long time, they also suppress the immune system, increasing the risk of infection and weakening the bones. Most of these side effects disappear over time after drug use is stopped. 

Bone-Modifying Drugs 

Bone modifying agents include a variety of drugs that prevent or treat damage from bone metastases in patients with cancer. The primary purpose of these agents is to prevent skeletal events such as pathological fracture, spinal cord compression, and hypercalcemia. Bone modifying agents can affect chronic pain from bone metastases. Most patients with myeloma are recommended bone-modifying medication to help strengthen bones and reduce bone pain and fracture risk. Two types of bone-modifying drugs are available to treat bone loss from multiple myeloma. 

• Bisphosphonates such as zoledronic acid (Zometa) and pamidronate (Aredia) block cells that dissolve bone called osteoclasts. 
• Denosumab (Xgeva) is an osteoclast-targeted therapy called a RANK ligand inhibitor. It is approved to treat multiple myeloma and may be a better option for people with severe kidney problems. 

Treatment with a bone-modifying drug is recommended for up to two years. If no results are obtained within this period, the treatment should be changed. The common side effects of bone-modifying agents are flu-like symptoms, which include anemia, joint and muscle pain, kidney problems, diarrhea, nausea, anemia, and back pain. 

Immunotherapy 

Immunotherapy drugs are also called biological therapy. It strengthens the body’s natural defenses to fight cancer. Cellular immunotherapies approved to treat multiple myeloma are idecabtagene vicleucel (Abecma) and skinacabtagene autoleucel (Carvykti). They can be used to treat multiple myeloma that has not been stopped with four or more treatments. Since different immunotherapy drugs are used in medicines, various side effects may occur. Common side effects include skin reactions, flu-like symptoms, diarrhea, and weight changes. 

Bone Marrow/Stem Cell Transplantation 

It is a medical procedure in which cancerous cells in the bone marrow are replaced with healthy cells. These cells are called hematopoietic stem cells. The blood-forming hematopoietic cells in the bloodstream and bone marrow transform into healthy red blood cells, white blood cells, and platelets in the bone marrow upon transplantation. There are two hematopoietic stem cell transplants: allogeneic (ALLO) and autologous (AUTO). ALLO uses donated stem cells in clinical trials, while AUTO uses the patient’s own stem cells. For multiple myeloma, AUTO is more commonly used. With both types, the goal is to destroy all cancer cells in the bone marrow, blood, and other parts of the body using high-dose chemotherapy (usually melphalan) and then allow the replacement of blood stem cells to create healthy bone marrow and boost the immune system. 

People undergoing intensive therapy may need to take a medicine called lenalidomide and a much higher dose of chemotherapy to help destroy more myeloma cells. Lenalidomide helps prevent myeloma symptoms from worsening or returning. 

Radiation Therapy 

Radiation therapy aims to rapidly shrink myeloma cells with high-powered energy beams from sources such as X-rays and protons to kill cancer cells. Radiation therapy is usually recommended when chemotherapy is not practical or when bone pain is under control. Side effects of radiation therapy can include fatigue, mild skin reactions, stomach upset, and loss of bowel movements. Most side effects go away soon after treatment ends. 

Surgery 

The surgical method is not one of the first options that come to mind in multiple myeloma disease. It is used to treat bone diseases only if there are fractures in the bone or recent plasmacytomas (a mass disease caused by myeloma cells collecting in one area and forming a tumor). Emergency surgery may also be required in cases where spinal cord compression causes paralysis, severe muscle weakness, or numbness. 

Sources: 

Nhs.uk 

Mayoclinic.org 

Cancer.net 

Cancer.org 

Multiple Myeloma Staging 

Multiple myeloma is a cancer that develops in the plasma cells of white blood cells. Antibodies that target and attack germs are produced by healthy plasma cells, which aid in fighting infections. Cancerous plasma cells accumulate in the bone marrow and drive out healthy blood cells in this disease. Instead of producing healthy antibodies, cancer cells create abnormal proteins that can cause complications in the body. 

Myeloma begins with a single abnormal plasma cell in your bone marrow, which is the soft, blood-producing tissue that fills the middle of most of your bones. The defective cell multiplies quickly. 

After a cancer diagnosis is confirmed, doctors will determine if it has spread, and if so, where. This process is called staging. The stage of cancer measures the extent of disease in the body. This provides insight into how serious the cancer is and the best way to treat it. Doctors also use the stage to calculate survival statistics. Laboratory, imaging, and bone marrow examination results are used to predict the disease’s progression and plan treatment. 

There are two methods of staging multiple myeloma, the Durie-Salmon Staging System, and the Revised International Staging System, which was created more recently and is used more often. 

If there is no evidence of the disease progressing or symptoms present in myeloma, it is called smoldering or asymptomatic myeloma. 

The Revised International Staging System 

The International Staging System (ISS) differs from the Durie-Salmon Staging System in the substances that are measured in the blood. This method measures the following proteins: 

• Beta2-microglobulin 
• Albumin  

The ISS has been updated to look for elevated levels of lactate dehydrogenase (LDH) or high-risk cytogenetic abnormalities to cover a comprehensive prognostic index. This is known as the Revised International Staging System. 

Durie-Salmon Staging System 

The myeloma stage is calculated using the Durie-Salmon Staging System by measuring: 

• Hemoglobin concentration 
• Blood calcium levels 
• Bone lesions on imaging tests during staging 
• M proteins in the blood and urine 
• Level of kidney function 

Stage I 

Durie-Salmon Staging System:  

• Hemoglobin concentration >10.5 g/dL 
• Serum calcium value normal or less than or equal to 12 mg/dL 
• X-ray studies of bone showing normal bone structure (scale 0) or solitary bone plasmacytoma only 
• Low M-component production rate 
• lgG value < 5 g/dL 
• lgA value < 3 g/dL 
• Urine light chains < 4 g/24 hours 

Revised International Staging System: 

• Serum albumin > 3.5 g/dL 
• Serum B2-microglobulin < 3.5 mg/L 
• No high-risk cytogenic features 
• Normal serum lactate dehydrogenase level 

Stage II 

Durie-Salmon Staging System:  

• Neither Stage I nor Stage II 
• A-No renal failure (creatine less than or equal to 2 mg/dL) 
• B-Renal failure (creatine greater than or equal to 2 mg/dL) 

Revised International Staging System: 

• Neither Stage I nor Stage II 

Stage III 

Durie-Salmon Staging System:  

• Hemoglobin concentration < 8.5 g/dL 
• Serum calcium value normal or > 12 mg/dL 
• X-ray studies of bone showing > 3 lytic bone lesions 
• High M-component production rate 
• lgG value > 7 g/dL 
• lgA value < 5 g/dL 
• Urine light chains > 12 g/24 hours 

Revised International Staging System: 

• Serum albumin > 5.5 g/dL 

And one of the following: 

• High-risk cytogenics 
• t(4;14) 
• t(14;16) 
• del (17p) 
• Elevated serum lactate dehydrogenase level 

The below terms are used in multiple myeloma staging results: 

• Del: deletion 
• dL: deciliter 
• g: gram 
• Ig: immunoglobulin  
• L: liter 
• M-component: monoclonal component 
• N protein: monoclonal (myeloma) protein 
• Mg: milligram 
• t: translocation between chromosomes 

Factors Other Than Stage That Affect Survival 

Staging is the main factor doctors consider when determining the prognosis or expected survival rate of a patient. Other factors include age, overall health, and kidney function. Overall, multiple myeloma has a five-year survival rate of 55 percent.  

Age: The older a myeloma patient is at the time of diagnosis, the worse the prognosis will be. 

Overall health: Doctors factor in a patient’s overall health when determining the survival rate or prognosis. Patients with other health complications such as diabetes and heart disease will often have a worse outlook than those who were healthy prior to their myeloma diagnosis. 

Kidney function: To measure the function of the kidneys, doctors will test the blood creatine levels, which is a chemical that is removed from the body by the kidneys. Patients who have a poor prognosis will have higher levels of creatine, due to damage in the kidneys from the monoclonal immunoglobin. An M spike occurs in myeloma patients when there is a large amount of an individual antibody present, which indicates the protein came from cells that originally started as one malignant cell. 

Bone marrow samples may be sent to analyze the chromosomes in the cancer cells, which is called cytogenetics. Certain chromosome changes can indicate a poor prognosis, such as a loss of a piece of chromosome 17, an exchange of material from chromosomes 4 and 14 (translocation), or a translocation involving chromosomes 14 and 16. 

Treatment for multiple myeloma depends on similar factors, including the stage, overall health, biomarkers, risk of treatment complications, and whether influences affecting the tolerance to treatment are present. 

Sources: 

https://www.lls.org 

https://www.cancer.org 

Multiple Myeloma Follow Up Care 

Multiple myeloma is one of the diseases doctors follow closely during and after treatment. Follow-up care aims to check whether cancer has come back, manage the side effects that may occur, and monitor the patient’s general health. Over time, myeloma may recur, even if treatment is finished. It is essential for follow-up care to work with a healthcare team that knows the patient’s medical history regarding previous treatments and the spread of the disease. Because the doctor knows the patient’s medical history, they can offer personalized treatment options to the patient. 

Follow-up care for myeloma patients can often continue for a long time, perhaps lifelong. Average follow-up care typically includes blood and urine tests, periodic imaging scans, and bone marrow evaluation every 1 to 3 months. 

If you experience bone pain, leg swelling, numbness or tingling in the feet and legs, various infections in the body, or other symptoms that are out of your routine after myeloma treatment, be sure to tell your healthcare team. In this case, your doctor may also perform different tests on you. In addition, inform your healthcare team about even the most minor health problem you will experience after the treatment. 

Creating a Survivorship Care Plan 

You may need to change your standard of living after treatment slightly. For this, your doctors can give you some advice. The survival plan should strongly consider including nutritional (or diet) and physical activity recommendations, information about possible long-term side effects from your treatment, regular follow-up examinations, and a program that can follow up tests. 

Managing Long-term and Late Side Effects 

Treatment methods and drug treatments for cancer patients usually cause side effects in most people. However, these may not appear immediately. Some patients may have symptoms that appear late or appear after many years. These are long-term side effects and may include physical and emotional changes. Since the patients are checked regularly by the healthcare team, doctors will guide them for the most appropriate treatment when an unexpected situation is seen in the body.  

Keeping Health Insurance and Copies of Your Medical Records 

All reports, test results, and material documents related to your cancer treatment are invaluable to healthcare professionals who will deal with you throughout your life. If you continue the follow-up process with a doctor who does not know your disease history after your cancer treatment is over, this information will be critical for the doctor to get to know you and create a new treatment form for you. In addition, you should pay attention to the coverage and continuity of your health insurance, as you will go to regular check-ups and have standard tests after the treatment. 

Can I Lower My Risk of Progressing or Coming Back? 

As with other cancer diseases, multiple myeloma is directly affected by the patient’s living conditions. Adopting a healthy lifestyle during and after treatment will reduce the risk of the disease coming back. In addition, a robust immune system, not smoking, exercising, avoiding the consumption of excessively fatty foods, and following a healthy diet are essential in maintaining your weight and keeping your body’s resistance strong.   

Setting Reasonable Goals 

While your follow-up care continues, support the treatment process that the doctors will apply by setting achievable goals for yourself. These goals may include gradually increasing the weekly exercise hours and preparing a suitable diet list for the weight you want to achieve or maintain. Although multiple myeloma is a challenging disease, it is up to you to make your life after the disease enjoyable. 

Sources:  

Mayoclinic.org 

Cancer.net 

Cancer.org 

Relapse in Multiple Myeloma 

Relapse is the reappearance of signs and symptoms of a disease after a period of recovery. Multiple myeloma may recur one or more times after treatment is completed.  

What Causes Relapse in Multiple Myeloma? 

It occurs when multiple myeloma affects infection-fighting white blood cells called plasma cells in your bone marrow. No matter how advanced the treatments are, they may not be enough to stop the abnormal and rapid proliferation of blood cells. Treatments may not wholly eliminate cancerous cells. In this case, the remaining cancer cells can become active again and begin to multiply.   

How Is Relapse Detected? 

In the case of recurrence, the same features as the multiple myeloma symptom may recur, or ultimately new symptoms may appear. According to the International Myeloma Working Group (IMWG), the symptoms defined for patients with recurrent multiple myeloma are as follows: 

• Bleeding 
• Bruising 
• Fatigue 
• Weakness 
• Infections 
• Bone pain 
• Definite increase in the size of existing plasmacytomas (tumors composed of plasma cells) or bone lesions 
• Hypercalcemia (> 11 mg/dL) above normal blood calcium levels 
• A decrease of ≥ 2 g/dL in hemoglobin in complete blood count tests (the protein in oxygen-carrying red blood cells)  
• Increase in serum creatinine (muscle waste product in the blood) of 2 mg/dL or more from the start of treatment and attributable to myeloma 
• Hyperviscosity (thickening of the blood) related to serum protein

What Are Tests to Monitor Relapse? 

Tests that can help doctors tell if myeloma has come back include: 

• Routine blood count 
• Routine urinalysis 
• Skeletal research with X-ray 
• MRI/CT scan for specific problems 
• Whole-body FDG/PET scan if disease status is unclear 
• Liver function test 
• Myeloma protein measurements 
• Bone density measurement (DEXA scan) as a baseline and to evaluate the benefit of bisphosphonates 
• Aspiration and biopsy for diagnosis and periodic monitoring of bone marrow   

What Questions to Ask the Doctor? 

If multiple myeloma has recurred, your doctor will re-create a treatment plan for you. In this plan, the following questions may come to your mind:  

• Why did you recommend this treatment?  
• What is different from previous treatment? 
• How can this treatment method help my cancer?  
• What side effects can it cause?  
• How can I manage my problems arising from treatment?  
• Will I need support, and where can I go for this?   

How Is Recurrent Multiple Myeloma Treated? 

A new treatment plan is prepared depending on the number of cancer cells and the proliferation rate. Issues such as the type and duration of previous treatments, the drugs used, and how cancer responds to these drugs are essential. If the doctors think you have received a treatment that gives fast results before, they may use the same treatment method or prefer a different approach.   

Some medications used to treat myeloma include: 

Proteasome inhibitors: Proteasomes are enzymes that help break down and remove damaged or unnecessary proteins inside cells. Multiple myeloma cells produce large amounts of abnormal proteins. Medicines are called proteasome inhibitors to prevent myeloma cells from breaking down these proteins. As the proteins accumulate, the cancer cell swells, eventually bursting open and dying. Proteasome inhibitors include: 

• Bortezomib (Velcade) 
• Carfilzomib (Kyprolis) 
• Ixazomib (Ninlaro) 

Immunomodulatory drugs: These drugs strengthen the body’s immune system (defenses against germs) to help it fight cancer. Medications include: 

• Lenalidomide (Revlimid) 
• Pomalidomide (Pomalist) 
• Thalidomide (Talomid) 

Steroids: These drugs reduce inflammation in the body and kill myeloma cells. It also relieves nausea and vomiting that can be caused by chemotherapy. 

Sources: 

Myeloma.org 

Webmd.com 

Multiple Myeloma Clinical Trials 

Multiple myeloma is a cancer that develops in the plasma cells of white blood cells. Antibodies that recognize and attack germs are produced by healthy plasma cells, which aid in the battle against infections.  

The goal of all cancer clinical trials, including those for multiple myeloma, is to find better treatments for patients. Enrolling in a clinical trial gives patients access to a team of doctors and nurses dedicated specifically to their care and treatment. Every aspect of patients’ health is closely monitored and analyzed to ensure the safety and effectiveness of the drug. 

What Are Clinical Trials? 

Multiple myeloma clinical trials test new and promising cancer treatments to diagnose, prevent, or treat a disease. Doctors use clinical trials to find treatments and improve life quality for patients with the disease. Clinical trials help to advance the field for the future by finding better alternatives to standard treatments, often with less side effects. 

Every cancer treatment used today went through 10-15 years of clinical trials before they can become adopted as standard treatments. By enrolling in clinical trials, cancer patients sign up to receive the latest, most cutting-edge care, with technology and treatments that won’t be publicly available for years. 

Treatments for multiple myeloma and other cancer types are expensive and time-consuming to develop. However, it is usually free for you to participate in clinical trials. Study sponsors, not the patients, often pay for the cost of clinical trial participation. Any other expenses incurred are frequently reimbursed such as travel and other accommodations. 

What Are the Phases of a Clinical Trial? 

There are clinical trial phases 1-4, and each phase takes a different amount of time and requires a different number of participants. 

• Phase 1: In this phase, 20-80 healthy people who have no underlying health conditions participate in the trial. The reason for this phase is so that researchers can determine if the drug causes any severe side effects to participants. It also helps researchers determine the safe dose that can be given to participants. According to the U.S. Food and Drug Administration (FDA), 70 percent of medications move to phase 2. 
• Phase 2: In this phase, hundreds of participants who have the condition the medication is developed to treat. These participants are monitored closely for several months or years to understand the effect the medicine has on the disease and if any side effects develop in participants with the condition. According to the FDA, 33 percent of medications move on to phase 3. 
• Phase 3: In this phase, a few thousand participants have the condition the medication is meant to treat. This phase usually lasts for several years. The purpose of this phase is to evaluate the effectiveness of the drug in comparison to other treatments for the same condition. This phase is typically required before the new drug can be approved by the FDA. According to the FDA, 25 to 30 percent of medications move on to phase 4. 
• Phase 4: In this phase, the FDA has approved the drug, and it can be used commercially but still requires additional long-term testing. This phase involves thousands of participants, takes place over several years, and is used to determine long-term safety and effectiveness. 

How to Find a Clinical Trial? 

Talk to your doctor about whether a clinical trial is right for you. Some patients are not eligible for certain clinical trials due to previous treatments, test results, biomarkers, and more. However, there are thousands of active clinical trials, each with different eligibility criteria. Many patients believe they are too old or won’t qualify for a multiple myeloma clinical trial. You can be of any age to participate in a clinical trial. In fact, 63 percent of cancer clinical trial patients are 65 years or older. 

Multiple myeloma patients can also find cancer clinical trials through the Synergy-AI Clinical Trial Matching System (CTMS). This artificial intelligence (AI) powered-platform searches through the vast number of clinical trials for personalized matches based on more than 170 clinical algorithms to find the best available treatments.  

How to Join a Clinical Trial? 

There are studies for every stage of multiple myeloma, and even studies for cancer prevention. Clinical trials allow access to up-and-coming therapies and are sometimes best when used as the first method of treatment. Once a patient is pre-screened to ensure they meet all the eligibility criteria, they can enroll and travel to the clinical trial site. 

Clinical trial participants are fully informed of the risks and benefits and are treated with respect and dignity, have had a positive experience, and would recommend a trial to others. Many participants receive extra attention compared to other hospitals because they receive more attention from nurses and study coordinators. 

If you decide you do not want to participate in the trial anymore, you can withdraw at any time. Patients have the freedom to continue or halt use of treatment at any point throughout the trial. 

Latest Research About Multiple Myeloma 

Doctors and researchers continuously explore new ways to learn more about multiple myeloma, how to prevent it, and the best way to treat it. 

Below are some of the areas of research currently in clinical trials available to multiple myeloma patients. Talk with your doctor to find out the best multiple myeloma treatment options for your individual case, and if a clinical trial is right for you. 

New drugs: In multiple myeloma, there is a difficulty in long-term treatment because, the cancer cells can become resistant to drugs. In clinical trials, new drugs are developed to target specific alterations or substances within cancer cells that overcome normal drug resistance. There are currently various drugs available for relapsed or refractory myeloma, advanced myeloma, and early-stage myeloma. 

• B-cell maturation antigen (BCMA): BCMA is a marker targeted on plasma cells for myeloma treatment. BMCA is targeted through antibodies that bring immune system cells to destroy myeloma cells, antibody-drug conjugates, and chimeric antigen receptor (CAR) T-cell therapies. 
• Venetoclax (Venclexta, Venclyxto): A BCL-2 inhibitor that may benefit myeloma with a specific genetic mutation that appears in about 20 percent of all patients. 
• MCL-1 inhibitors: These drugs destroy cancer cells in myeloma for patients with MC-L1 mutations present. 
• New Drug combinations: Due to the resistance of treatment in patients after roughly a year, combinations of drugs are being studied. These include: 

• Bortezomib and lenalidomide in combination with dexamethasone 
• Bortezomib, cyclophosphamide, and dexamethasone 
• Carfilzomib, lenalidomide, and dexamethasone 
• Ixazomib, lenalidomide, and dexamethasone 
• Pomalidomide, bortezomib, and dexamethasone 
• Carfilzomib, pomalidomide, and dexamethasone 
• Pomalidomide, ixazomib, and dexamethasone 
• Pomalidomide, dexamethasone, and clarithromycin (Biaxin) 
• Daratumumab, bortezomib, dexamethasone 

Immunotherapy: This type of cancer treatment naturally or artificially made boosts the body’s natural defenses to fight cancer. 

• CAR T-cell immunotherapy: Immune cells are removed from the patient, altered in a laboratory to attack myeloma cells, and then injected back into the patient. The FDA has already approved one CAR T-cell therapy called idecabtagene vicleucel. BCMA-targeted CAR T cells in combination with other treatments are being examined in clinical trials to treat multiple myeloma. 
• Immune checkpoint inhibitors: These targeted drugs target biomarkers in cancer cells and prevent them from performing vital cell functions, killing the cancer cell. PD-1 is located on T-cells and prevents the immune system from attacking cancer cells. Targeting PD-1 in treatment leads to the immune system attacking cancer cells. 
• Bispecific T-cell engagers (BiTEs): There are clinical trials using these monoclonal antibodies to target BCMA and activate a response from the immune system to attack cancer cells by attaching to T-cells and myeloma cells. BITEs are artificially made but there is no need to remove the patient’s immune cells like CAR T-cells.  
• Cancer vaccines: Vaccines are considered a type of immunotherapy that is being evaluated for treating multiple myeloma.  

Palliative care/supportive care: A few active clinical trials aim to discover better ways of reducing symptoms or side effects of myeloma treatments to improve the quality of life for patients. 

Sources: 

https://www.myeloma.org 

https://www.cancer.net