What is Multiple Myeloma?
Multiple myeloma is a disease where a particular type of white blood cell, known as a plasma cell, grows out of control in your body and creates an abnormal amount of proteins called monoclonal immunoglobulins. If left unchecked, these rapidly multiplying plasma cells can lead to damage in specific parts of the body. Common signs of this damage can include high calcium levels in the blood (hypercalcemia), kidney problems (renal dysfunction), a low red blood cell count (anemia), or bone pain with areas of bone destruction (lytic lesions).
Of course, these symptoms could be an indication of many different medical conditions. However, it’s vital to consider multiple myeloma because the disease requires unique treatment methods. Timely detection and treatment can significantly enhance the health outcomes for a person with this condition.
What Causes Multiple Myeloma?
The exact cause of multiple myeloma, a kind of cancer that begins in a type of white blood cell called a plasma cell, is unclear. That being said, changes and rearrangements in certain genes, particularly chromosome 14, are often detected in patients with this condition. These alterations may contribute to the development of the disease.
In addition to that, there are other genes like NRAS, KRAS, and BRAF that may play a part in plasma cell growth. Growing too many plasma cells can lead to multiple myeloma. Besides these genetic factors, the risk of getting this disease can also be influenced by conditions such as obesity and alcohol consumption.
Certain environmental factors have also been linked to multiple myeloma. These include things like insecticides, organic solvents, and a herbicide called agent orange. Being exposed to radiation is also a potential risk factor.
Risk Factors and Frequency for Multiple Myeloma
Multiple myeloma, a type of cancer, is not very common. It makes up about 1.8% of all new cancer diagnoses in the United States each year. This disease primarily affects older people, with an average age at diagnosis of approximately 70. It’s slightly more common in men than in women. Interestingly, it appears that African American and black populations have twice the incidence compared to white populations.
Signs and Symptoms of Multiple Myeloma
Multiple Myeloma (MM) can have various symptoms and often shows up differently in people. Generally, it’s seen in older adults and can cause a range of issues. Common symptoms include anemia, bone pain, kidney problems, fatigue, high calcium levels in the blood, and weight loss. The percentage of how often these symptoms occur in newly diagnosed MM patients are as follows:
- Anemia (73%)
- Bone Pain (58%)
- Increased levels of creatinine, indicating kidney issues (48%)
- Fatigue (32%)
- High calcium levels in the blood (28%)
- Weight Loss (24%)
Specifically, high calcium levels caused by bone deterioration can lead to a slew of symptoms like increased thirst and urination, bone pain, stomach pain, nausea or vomiting, and changes in thinking or reasoning. Kidney failure (resulting from high calcium levels and certain types of kidney diseases), can cause swelling, imbalance of acid in the body, and disturbances in electrolyte levels. Anemia can cause you to feel tired, look pale, have heart palpitations, and worsens pre-existing heart conditions. Bone pain due to MM can lead to fractures, height loss, spinal cord compression, shooting pain, or create a hunchback-like curvature in the spine.
Although less common, some patients might experience peripheral neuropathy (nerve damage causing tingling and numbness) or carpal tunnel syndrome. If these symptoms are spotted, additional tests are necessary as these are often connected to a condition called amyloidosis. It’s also uncommon, but symptoms of hyperviscosity (thick blood) may be present, typically leading to bleeding, confusion, neurological symptoms, vision changes, or heart failure. It is vital to identify these situations as they are medical emergencies. Lastly, individuals with MM may be more susceptible to infections, especially pneumonia and kidney infection, so regular check-ups for any recurring illnesses are important.
Testing for Multiple Myeloma
Multiple myeloma is a disease that is part of a group of disorders affecting your plasma cells (a type of white blood cell that makes antibodies). To correctly categorize and manage the disease, it’s categorized into MGUS (a condition where there are abnormal plasma cells but usually no symptoms or problems), smoldering myeloma (an intermediate stage between MGUS and myeloma, again with no symptoms), and symptomatic multiple myeloma (where actual symptoms and complications occur). The treatment differs according to these categories, so it’s important to correctly identify which one you have if multiple myeloma is suspected.
If your doctor suspects multiple myeloma, they may use several methods for testing and diagnosis, based on guidelines from the National Comprehensive Cancer Network (NCCN).
These tests may include:
* Blood and platelet count
* Tests for kidney function, electrolyte levels, protein levels, and calcium levels in your blood
* Specific proteins in the blood that might indicate myeloma
* Tests for proteins in the urine
* A test for light chains proteins (abnormal amounts can be a sign of myeloma)
* Imaging tests like low-dose CT or PET CT
* Taking a sample of bone marrow (the spongy tissue found in the center of your bones where blood cells including plasma cells are made) for testing
* Specific genetic tests on the plasma cells
Traditionally, multiple myeloma was diagnosed when a bone marrow sample showed 10% or more plasma cells were abnormal (or a plasmacytoma, a single area of abnormal plasma cells, was found), along with at least one of four criteria (known as the CRAB criteria): high calcium levels in the blood, kidney problems, anemia, or specific types of bone damage.
However, this method sometimes missed cases that needed treatment. So, in 2014, some additional factors were added to these criteria to help catch more cases of myeloma. If you have 60% or more abnormal plasma cells, a 100 times or higher ratio of involved to uninvolved free light chain proteins in the blood, or more than one area of bone damage (each over 5 mm) on an MRI scan, these can now also justify a diagnosis and starting treatment for multiple myeloma.
By incorporating these new factors, this diagnosis method, often referred to as SLiM CRAB, has become more sensitive and identifies more cases that require treatment.
Treatment Options for Multiple Myeloma
Initially treating multiple myeloma, a type of bone marrow cancer, involves dealing with any immediate complications that could be life-threatening or severely detrimental to the patient’s health. This might include the use of a fluid replacement therapy with isotonic saline, which helps balance the body’s fluid levels. It could also include the use of medications such as calcitonin and bisphosphonates to control high levels of calcium in the bloodstream, a condition known as severe hypercalcemia. High calcium levels can cause numerous health issues, including kidney problems.
If the patient shows significant kidney malfunction, our focus shifts to optimizing the patient’s health. This could involve consulting with kidney specialists to address the patient’s fluid balance, avoid any drugs that are harmful to the kidneys, and adjust the dosages of necessary medications in a way that protects the kidneys. In severe cases, the patient might require dialysis—a process that filters waste products from the blood when the kidneys can’t.
If the cancer results in a spinal cord compression due to a vertebral fracture or plasmacytoma (a tumour formed by plasma cells), emergency treatment is needed. This involves doctors who specialize in treating the brain and spine, or bone experts, and possibly radiation therapy (a powerful X-ray that kills cancer cells).
Once the patient’s condition is stabilized, the treatment plan shifts focus based on how severe the disease is and whether a patient is eligible for a stem cell transplant—a procedure that can potentially cure the disease. A patient’s disease can be classified as high-risk or standard-risk, determined by a test called fluorescence in situ hybridization (FISH) that identifies genetic abnormalities in cells. This helps the doctors make decisions on the best course of treatment.
Stem cell transplant eligibility is decided case by case, but usually, patients above 77 years old, those with a severe liver disease called cirrhosis, those with a certain level of functional health status (ECOG performance status of 3 or 4), or those suffering from severe heart failure are considered ineligible for the transplant.
Patients who are fit for transplant typically receive induction therapy for 3 to 4 months. This is a pre-transplant treatment designed to decrease the tumor’s size. This then leads to the collection and transplantation of the patient’s own stem cells, which has been shown to improve survival rates. This transplant can be performed early after recovery from stem cell collection or delayed until the cancer grows again. After the transplant, the patient will continue ‘maintenance’ medication until the disease progresses or they can no longer tolerate the treatment.
The type of induction therapy, and the drugs that will be used continues to be a detailed calculation taking into account individual patient factors. If a patient has high-risk disease, doctors might consider therapy from a pool of drugs followed by an early stem cell transplant. This is followed by maintenance therapy until disease progression.
For patients with standard-risk multiple myeloma who are eligible for transplantation, four cycles of induction therapy are followed by stem cell transplantation and then maintenance therapy with a drug until disease progression occurs.
For high-risk patients who are not eligible for transplantation, there are multiple options. One approach is to undergo 8 to 12 cycles of therapy with drugs followed by maintenance therapy. Alternatively, patients can be given a different combination of drugs until the disease progresses.
For standard-risk patients who are not eligible for transplantation, options include 8 to 12 cycles of therapy followed by maintenance therapy, or a different combination of drugs until the disease progresses.
What else can Multiple Myeloma be?
When trying to diagnose multiple myeloma – a type of blood cancer – doctors have to consider a number of other conditions that can cause similar vague symptoms. It’s crucial to rule out these conditions before a final diagnosis is made. These other conditions might include:
- Monoclonal Gammopathy of Undetermined Significance (MGUS) – This is characterized by a serum monoclonal protein less than 3 g/dl, clonal bone marrow plasma cells less than 10%, and no evidence of damage to body organs.
- Smoldering Multiple Myeloma – Symptoms include a monoclonal protein level that is greater than or equal to 3 g/dl, clonal bone marrow plasma cells between 10% to 59%, and again, no damage to body organs.
- Solitary Plasmacytoma – This condition features a solitary lesion made up of clonal plasma cells, normal bone marrow, and no positive imaging outside of the single lesion. Just like the previous two conditions, there’s no damage to the organs.
- Waldenstrom Macroglobulinemia – This presents with lymphoplasmacytic lymphoma in the bone marrow, the type of M protein is IgM which is unusual in multiple myeloma, presence of MYD88 L265P mutation, and symptoms like high blood viscosity, peripheral neuropathy, anemia, swollen lymph nodes, and enlarged liver or spleen.
- AL Amyloidosis – This disorder is caused by deposition of amyloid fibrils or non-fibrillar material leading to heart failure, enlargement of the liver, and/or nephrotic syndrome. There are less than 20% plasma cells in the bone marrow and there’s a lack of lytic lesions. Congo-red staining on bone marrow or affected tissue is a telltale sign.
These conditions are different from multiple myeloma and must be ruled out in order to arrive at an accurate diagnosis.
What to expect with Multiple Myeloma
The outlook for multiple myeloma, a type of blood cancer, can vary greatly depending on several factors. The two main elements affecting this are the stage of the cancer and the nature of the disease itself.
The R-ISS stage system was developed to evaluate newly diagnosed cases of multiple myeloma. This was based on 11 international trials. The research found that for stage I of the disease, around 82% of patients survived for at least five years, and around 55% did not experience disease progression in that time. For stage II, the five-year survival rate dropped to 62%, with 36% avoiding disease progression. Lastly, in stage III, the five-year survival rate was 40% and around 24% did not see their disease progress over that period.
Genetic abnormalities that are considered high risk can worsen the patient’s outcome. Abnormalities like 4:14, 14:16, and 14:20 have been shown to reduce survival rates. One study found that a specific abnormality, t(14:16), led to, on average, 2.1 years without disease progression and a total survival of 4.1 years. Another speed-bump can be deletions on chromosome 17p, which often teams up with mutations in a gene called TP53. When these two team up, studies have shown the average time to disease progression is about 18.1 months, with overall survival around 36 months.
These factors help us understand the general outlook for people with multiple myeloma and can guide discussions with patients. It’s important to remember, though, that these are average observations and individual outcomes can vary. Also, treatment for multiple myeloma has significantly improved over the recent years and these improvements may not yet be fully reflected in the survival stats mentioned above.
Possible Complications When Diagnosed with Multiple Myeloma
Multiple myeloma, a type of cancer that affects plasma cells, can result in a range of health problems. Common issues include high levels of calcium in the blood, kidney problems, infections, bone damage, and anemia. Less frequently, it can cause blood clots and a syndrome characterized by unusually thick blood (hyperviscosity syndrome).
High calcium levels are usually due to bone breakdown and can cause different symptoms, including loss of appetite, tiredness, constipation, excessive thirst and urination, confusion, and even unconsciousness. Different treatments are used depending upon the severity and speed of development. Options include staying well-hydrated, steroid medication, medications that slow the breakdown of bones, thyroid hormone therapy, and dialysis if needed.
Kidney problems may develop slowly or suddenly in multiple myeloma patients. There can be several causes, including excessive production of a component of antibodies, deposition of these components in kidneys, high calcium and uric acid levels, or dehydration.
Multiple myeloma can affect bones, leading to bone breakdown, calcium release into the blood, hypercalcemia, and kidney failure symptoms. This might present as severe bone pain, fractures, and even spinal cord compression.
Infection risk is also a common complication, highest during the initial months of treatment. The immune system is often weakened due to lymphocyte dysfunction, suppression of normal plasma cells, low levels of antibodies, and a decrease in white blood cells due to chemotherapy. Common infections are pneumonia and urinary tract infections, caused by specific types of bacteria. It is vital to identify and treat these infections early.
Some patients experience nerve damage, which can be due to the disease itself, direct pressure, or component deposition. Yet, medications used for treatment can also cause or worsen it.
Blood clot risk can rise due to the patient’s pre-existing health problems, the disease, and specific drugs. If there are any signs of blood clots, an evaluation should be carried out immediately.
A rare but serious side-effect is hyperviscosity syndrome, characterized by excessively thick blood. This can manifest through nosebleeds, blurred vision, bleeding into the retina of the eyes, seizures, other neurological symptoms, confusion, shortness of breath, and heart failure. This is a medical emergency and requires immediate treatment, such as plasmapheresis (a procedure to filter the blood).
Likely complications include:
- High levels of calcium in the blood
- Kidney problems
- Infections
- Bone damage
- Anemia
- Blood clots
- Hyperviscosity syndrome
- Nerve damage
Preventing Multiple Myeloma
Understanding your health condition is a key part of managing multiple myeloma, a type of cancer that can be hard to grapple with. Your chances of getting better can increase if proper treatment is started as early as possible. This means you need to be actively involved and informed about your treatment options, so you can make decisions together with your doctor. This can help you stick to your treatment plan better.
Sadly, survival rates appear to be lower among African Americans compared to white people. Why this is the case isn’t fully known, but it does seem that African Americans often have less opportunity and access to the healthcare and treatment they need. Because of this, it’s crucial that communities are provided with proper outreach and education. By earning the trust of the community and improving access to healthcare, we can reach those who need it, especially those from this demographic.
