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Multiple myeloma is a cancer of the immune system that affects bone marrow and blood.
When a bacteria or virus invades the body, plasma cells—a type of white blood cell found in bone marrow—fight back, creating special proteins (known as antibodies or immunoglobulins) that eliminate or disable the germ causing the infection.
But, as with other cancers, the process may malfunction and cause the bone marrow to produce an excess of plasma cells derived from a single cell that has transformed into a malignant cell. This is referred to as a clonal cell. These cells can produce special types of proteins called cytokines that stimulate breakdown of bone, leading to the formation of holes in the bone known as lytic lesions. These lesions weaken the bone and can lead to fracture. Because multiple bone lesions can form, this condition is known as multiple myeloma.
Malignant plasma cells can also secrete a single type of antibody or immunoglobulin known as monoclonal or ‘M’ protein that can be detected in the blood and/or urine. Overgrowth of these cells can cause significant decrease in the ability of the bone marrow to make normal cells. This can result in anemia, a condition which impairs oxygen delivery throughout the body.
Multiple Myeloma Risk Factors
The greatest risk of multiple myeloma occurs with advancing age, with the average age of onset at around 70. Men are at a slightly higher risk than women. Risk increases fourfold if a patient has a first-degree relative who has been diagnosed with the disease. It is also more than twice as prevalent in African Americans.
Obesity can be a risk factor for myeloma as well, likely due to the patient’s long-term exposure to lipids or fat molecules. Myeloma is the most common cancer observed in patients with Gaucher disease, a lipid storage disorder.
Although not well understood, a patient’s environment may also be a contributing factor—the disease is sometimes found in regional clusters, among people who are unrelated other than by location. And while myeloma is one of the few cancers not caused by tobacco, smoking may complicate treatment, especially when underlying conditions like diabetes and heart disease are present as well.
Today’s myeloma patient has an excellent chance to lead a full life for a long time. Treatment is advancing dramatically, with promising developments on the horizon. https://bit.ly/3wjh9YU via @MedStarWHC
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Multiple Myeloma Symptoms and Diagnosis
The most common symptom of multiple myeloma is severe pain, often occurring in the back, hips, or legs. In addition, patients may report fatigue due to anemia or high calcium levels. Less commonly, the disease may also cause unexplained weight loss.
In addition, proteins known as light chains secreted by dysfunctional plasma cells can damage the kidneys. And as myeloma attacks bone, calcium is released into the bloodstream, which can also affect kidney function.
Back or hip pain from myeloma may occasionally be mistaken for a sprain, slipped disc, or other spinal problem. However, routine blood and urine testing can give clues to the diagnosis of multiple myeloma, thus facilitating an earlier diagnosis even before bone damage can begin. This underscores why everyone should seek regular health checkups from a healthcare professional, and why we must work to increase access and affordability to routine care for all segments of the community.
To make a clear diagnosis, we of course begin with a comprehensive physical exam and patient history. In addition to blood and urine tests performed in-office or at the Emergency Department, we order lab tests that look for abnormal proteins. An X-ray can assess bone involvement and, where there’s evidence of multiple lesions, an MRI or PET study can provide a better picture.
When these initial tests point to a possible diagnosis of myeloma, we obtain definitive information from specialized blood and urine testing and importantly, a bone marrow biopsy, where a small sample is taken for lab analysis. The sample helps make a diagnosis of myeloma and also obtains important genetic information about the disease, which helps determine prognosis and guide treatment.
Multiple Myeloma Treatment and Management
Initial treatment of myeloma consists generally of a three-drug regimen that is administered on an outpatient basis. Two of these drugs are taken orally and one is given subcutaneously. They are generally well tolerated, cause little to no nausea and do not result in hair loss. The treatment is given for several cycles and the effect of treatment is assessed at the end of each cycle. This is done via a series of blood and urine tests that assess the levels of monoclonal proteins. As the myeloma cells are killed, the levels of these proteins should diminish accordingly. After about four monthly cycles of this treatment, appropriate patients are then referred for a process known as “high-dose therapy.”
Many patients are candidates for a procedure known as high-dose therapy with stem cell rescue, which has also been referred to as an “autologous bone marrow transplant.” During this process, a chemotherapy drug known as melphalan is given at high doses to target these malignant plasma cells. This agent excels at destroying the residual myeloma cells not killed by the initial cycles of chemotherapy. However, because the chemotherapy can also damage healthy cells, we follow treatment with stem cell rescue.
We prefer the term stem cell rescue since the word transplant can create the impression that a donor is needed. In reality, the stem cells are the patient’s own, harvested before high-dose melphalan and deep-frozen for safekeeping.
The day after the high-dose melphalan is given, we then reset and restore the immune system by infusing the preserved stem cells a day after high-dose melphalan is given. The stem cells find their way back to the bone marrow, where they restore normal blood-forming elements within a couple weeks.
During this time, the patient remains in isolation at the hospital to reduce any risk of infection. Preventive antibiotics and blood transfusions also support the patient’s recovery, and we may readminister inoculations that may have been deactivated by the process, including vaccines against pneumonia, shingles, flu, and COVID-19.
Following the isolation period, the patient is placed into maintenance treatment, receiving lower doses of medications that delivered the most promising results, as well as medications to support immune health and bone strength. During this maintenance period, we carefully monitor myeloma markers for any evidence of disease resurgence.
If myeloma returns, the treatment strategy varies. Some patients do well with a second stem cell harvest and rescue. We have good data on which drugs work best in relapsed patients and can develop an effective combination of medications that will address the relapse and be well tolerated by the patient. Apart from ongoing monitoring, most myeloma patients are able to live fairly normal lives, with few restrictions on low-impact exercise and other activity.
A Promising Future
While combining chemotherapy and stem cell rescue is currently our best treatment strategy, studies are underway to determine the effectiveness of chemotherapy alone. Research is ongoing, robust, and exciting, and MedStar Washington Hospital Center has participated in trials for several drugs now in use.
The wave of the future is targeted therapy, for myeloma as well as other cancers. Agents such as the new monoclonal antibodies daratumumab, isatuximab, and elotuzumab can accurately identify, target, and destroy cancer cells without harming healthy cells.
Another effective medication, belantamab mafodotin, latches onto cancerous cells and introduces a specific toxin that kills just those cells. Also on the horizon are bispecific T-cell engagers, or BiTE agents, which can direct T cells to detect and destroy tumor cells. These agents are not yet approved, but the research is very promising.
A challenging aspect of myeloma is the fact that it behaves differently in each individual. Here at MedStar Washington Hospital Center, our team of hematologists, radiation oncologists, orthopedic oncologists, and pathologists is committed to tailoring management of this disease accurately and effectively. A diagnostic board meets weekly to discuss challenging or significant cases. The team also collaborates closely with cardiologists for patients with heart issues, and with our orthopedic surgeons for patients who need surgery to stabilize affected parts of the skeleton.
Years ago, multiple myeloma life expectancy was only three years from diagnosis. Today, with the right care, patients can live much longer.
Like all cancers, of course, the earlier we can begin to treat a patient, the better our chance of making a positive difference. The best way to beat a disease like multiple myeloma: stay regularly connected with your medical professional, and don’t skip your annual physical and lab tests.