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Plasma Cell Leukemia: Causes, Symptoms, And Treatments
Plasma cell leukemia (PCL) is a rare, aggressive subtype of multiple myeloma. Between 1973 and 2009, it's estimated that PCL made up 0.6 percent of multiple myeloma diagnoses in the United States. This is about 1,200 new diagnoses each year.
In PCL, high numbers of plasma cells are found in the blood and bone marrow. Plasma cells are antibody-producing immune cells that develop from activated B cells. There are two types of PCL: primary and secondary.
Primary PCL is a newly diagnosed blood cancer, making up 60 to 70 percent of PCL diagnoses. It has different genetic and molecular markers to secondary PCL. The average age at diagnosis is 61, about 10 years younger than multiple myeloma.
Secondary PCL is when multiple myeloma transforms into PCL. It makes up 30 to 40 percent of PCL diagnoses. Secondary PCL has been increasing, likely due to advances in multiple myeloma treatment. The average age at diagnosis is 66.
Multiple myeloma also affects plasma cells. In multiple myeloma, as in PCL, plasma cells grow and divide out of control.
However, in multiple myeloma, abnormal plasma cells remain confined to the bone marrow. In PCL, these cells spread out into the bloodstream.
Traditionally, PCL is defined by the number of plasma cells circulating in the blood. These criteria can include:
However, it's also possible that lower cutoffs for plasma cell numbers can be used to diagnose PCL. Genetic and molecular analyses may also be performed.
The exact cause of PCL is unknown. Similar to other cancers, PCL develops due to a series of genetic changes whose presence can lead to the emergence of abnormal cells that grow and divide out of control.
What exactly triggers these genetic changes to occur is unknown. Additionally, the mechanism by which abnormal plasma cells escape from the bone marrow and enter the bloodstream is also unclear.
The exact reasons for these differences are currently unknown but may be due to inequities in healthcare. As we learn more about PCL, it's possible we'll find out more about these as well as discover additional risk factors.
Because PCL is so rare, most of what we know about its symptoms comes from various case studies. Many of the symptoms of PCL are associated with organ damage due to the high numbers of abnormal plasma cells in the blood.
The potential symptoms of PCL can include:
The goal of PCL treatment is to lower the numbers of plasma cells in the blood and bone marrow, ideally achieving complete remission. Because PCL is very aggressive, it's important that treatment begin as soon as possible.
Let's take a look at how PCL may be treated.
Induction
The initial step of treatment is called induction. The goal of induction is to help reduce the number of cancer cells in the body.
The targeted therapy drug bortezomib (Velcade) is often used during induction. It may also be used as a part of combination therapy consisting of the immunomodulator lenalidomide (Revlimid) and the steroid dexamethasone.
Stem cell transplant
A doctor may recommend stem cell transplant as a part of PCL treatment. Typically, good candidates for a stem cell transplant are younger in age and in otherwise good health.
Autologous stem cell transplants are typically used. This is where healthy stem cells are harvested from your own body prior to the transplant, rather than from a donor.
Prior to a stem cell transplant, a high dose of chemotherapy is used to kill the cells in your bone marrow. This destroys both healthy and cancerous cells.
Then, you'll receive an infusion of the previously harvested stem cells. The goal is for these cells to settle in your body and set up healthy bone marrow.
It's also possible that a tandem stem cell transplant may be recommended. This involves receiving two autologous stem cell transplants in a row. Receiving a tandem stem cell transplant may help to improve overall survival.
Maintenance therapy
Maintenance therapy occurs after a stem cell transplant. If you're not eligible for a stem cell transplant, you may receive maintenance therapy after induction therapy.
The goal of maintenance therapy is to help to prevent cancer from coming back or relapsing. It typically involves the use of bortezomib, lenalidomide, or both.
Supportive treatment
Supportive treatments help to address the symptoms or complications associated with PCL and its treatment. Some examples of supportive treatments that may be given as a part of your PCL treatment include:
PCL is an aggressive form of cancer. It may initially respond to treatment, but quick relapses are not uncommon.
Individuals with PCL have an average overall survival of between 4 and 11 months. However, the increased use of autologous stem cell transplants as well as advances in treatments have slightly improved this number.
Some factors that have been found to worsen PCL outlook include:
When we talk about outlook, it's important to remember that overall survival statistics are based on the observation of many people with PCL. They don't reflect individual situations.
PCL is a rare and aggressive subtype of multiple myeloma. In PCL, abnormal plasma cells grow and divide out of control in the bone marrow and have spread into the bloodstream.
The treatment for PCL can involve various medications with or without a stem cell transplant. Relapses after treatment are common.
While the outlook for PCL is poor, it can be improved with prompt diagnosis and treatment. If you develop concerning signs or symptoms that are consistent with those of PCL, be sure to see a doctor as soon as possible.
What Does Multiple Myeloma Mean?
Multiple myeloma is a chronic blood cancer affecting plasma cells, but with today's treatments many patients can manage symptoms and live fulfilling lives.
What Does Multiple Myeloma Mean?Multiple myeloma is a cancer that begins in a type of white blood cell called plasma cells. These cells are found in the bone marrow and are responsible for producing antibodies, which are also known as immunoglobulins, that help fight infections. When a person has multiple myeloma, these plasma cells become cancerous and multiply uncontrollably.
This leads to an overproduction of an abnormal antibody called the M protein, which doesn't serve a useful function. The cancerous plasma cells can also crowd out healthy blood cells in the bone marrow and release substances that cause bone damage.
Multiple myeloma is not a solid tumor like breast or lung cancer. Instead, it's a type of blood cancer that can affect how multiple parts of the body work, including the bones, kidneys, and immune system. The disease is considered chronic, which means that while it can't typically be cured, it can be managed for many years with effective treatment.
How Is Multiple Myeloma Diagnosed?Diagnosis often begins with a routine blood test showing high levels of protein or calcium, or with a patient experiencing symptoms like bone pain or fatigue. The diagnostic process involves several tests to confirm the presence of myeloma and determine its extent.
"The diagnosis of myeloma is very often delayed," Dr. Joseph Mikhael, a professor in the Applied Cancer Research and Drug Discovery Division at the Translational Genomics Research Institute, an affiliate of City of Hope Cancer Center, and chief medical officer of the International Myeloma Foundation, said in an interview with CURE. "On average, people see their primary care provider three times with signs and symptoms consistent with multiple myeloma before the diagnosis is made."
How Is Multiple Myeloma Treated?The treatment for patients with multiple myeloma is highly personalized and depends on several factors, including the patient's age, overall health, and the specific characteristics of their myeloma cells. The goal of treatment is to reduce the number of cancerous cells, control symptoms, and prolong remission.
Examples include Darzalex (daratumumab) and Sarclisa (isatuximab), which both target the CD38 protein on myeloma cells, and Empliciti (elotuzumab), which targets the SLAMF7 protein.
Monoclonal antibodies are now a standard part of treatment for many newly diagnosed patients. Specifically, the anti-CD38 monoclonal antibody Darzalex has revolutionized the initial treatment of patients with multiple myeloma. Clinical trials have shown that adding Darzalex to standard-of-care regimens significantly improves outcomes. Specifically, its injection form, known as Darzalex Faspro (daratumumab and hyaluronidase-fihj), makes treatment time faster and has become more common than the original intravenous formulation.
"These are exciting times in cancer therapy in general and in particular in multiple myeloma, where, historically, we had to use the sorts of treatments that were tough on the patient, not just tough on their myeloma," Mikhael said. "But now we have come to an era where we can be much more targeted."
Other novel classes of agents, such as CAR T-cell therapy and bispecific antibodies, which are showing promising results for patients who have relapsed or are refractory to other treatments, are being explored in earlier disease settings.
Multiple Myeloma Treatment-Related Side EffectsTreatments for multiple myeloma can cause various side effects. It's important to discuss these with your oncologist, as many can be managed with supportive care.
A diagnosis of multiple myeloma can be overwhelming, but it's important to remember that it's a very treatable cancer. Your treatment plan will be carefully tailored to your specific needs, and with ongoing research, new and more effective therapies are becoming available. This overview is just the beginning of your journey.
"The year 2025, especially, has been a good one, and we have so many good immunotherapies now that we didn't have in the past, that I give new patients optimism. I use myself as an example," Dr. Jim Omel, a retired family practitioner from central Nebraska diagnosed with multiple myeloma in 1997, told CURE. "I'm an outlier when it comes to living that long, but new patients now can expect long, healthy lives. I use the analogy of diabetes. We cannot cure diabetes, but you can live with it, and we have good treatment for it. So I say that myeloma now is, for the majority — not all — but for the majority of patients, a chronic disease. You can live with it and enjoy your life."
The most important step you can take is to partner with your healthcare team. Ask questions, share your concerns, and be open about any side effects you experience. This will help your oncologist and you make the best decisions for your care, ensuring you have the highest quality of life throughout your treatment.
Interested in learning more about your multiple myeloma diagnosis? Hear firsthand a multiple myeloma survivor share his story surrounding his 1997 cancer diagnosis and how his cancer journey has evolved.
This guide is designed to be a starting point. Your personal experience will be unique. By using this information as a foundation for your discussions, you can partner with your oncologist to make the best decisions for your health.
Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice. Please contact your healthcare team with any questions or concerns.
For more news on cancer updates, research and education, don't forget to subscribe to CURE®'s newsletters here.
A Guide To Multiple Myeloma: Symptoms, Treatment And Prognosis
You don't expect to break a rib while doing light housekeeping. Similarly, you wouldn't think your worsening back pain might…
You don't expect to break a rib while doing light housekeeping. Similarly, you wouldn't think your worsening back pain might be caused by a type of blood cancer. However, these are among classic scenarios for patients who develop multiple myeloma, a type of blood cancer with multiple effects on your health. It disrupts your ability to fight infections, weakens once-healthy bones and potentially leads to kidney failure.
Multiple myeloma, sometimes called plasma cell myeloma or simply myeloma, is a relatively uncommon cancer, accounting for about 1% of all cancer cases.
Many patients with myeloma respond well to treatment, starting with strategically combined medications, followed by a stem cell transplant and, eventually, ongoing maintenance therapy to stave off myeloma's return.
There is no cure for multiple myeloma. Unfortunately, relapse is the rule rather than the exception with multiple myeloma. Within a decade, the vast majority of patients will have their cancer come back in full force and again need intensive treatment. Fortunately, as therapies keep improving, remissions are getting longer.
[READ: Immunotherapy for Blood Cancer.]
What Is Multiple Myeloma?
Blood is made up of red blood cells, platelets and white blood cells. Multiple myeloma is a cancer of a specific type of white blood cells called plasma cells.
Normally, plasma cells help the body fight infections. Plasma cells are produced in the bone marrow and make antibodies, Y-shaped proteins that protect the body from disease.
With multiple myeloma, the body makes too many irregular plasma cells, overproducing an abnormal antibody called a monoclonal protein, or M protein. These proteins build up in the bone marrow, causing damage to the bones. The kidneys usually help filter these types of proteins out, but with multiple myeloma, the kidneys become overwhelmed.
The disease is called "multiple" myeloma because these cancerous plasma cells build up in the bone marrow and form multiple tumors in different bones throughout the body.
Causes and Risk Factors
For the vast majority of cases, we do not know the cause of myeloma, says Dr. Joseph Mikhael, the Scottsdale-based chief medical officer of the International Myeloma Foundation.
Here is what we do know about possible causes and risk factors for myeloma, according to Mikhael:
— Myeloma is more common in older adults, with the average diagnosis around age 69.
— Individuals of African descent are twice as likely to contract myeloma.
— Men are more likely to be diagnosed with myeloma than women
— Certain environmental exposures are connected to myeloma, such as Agent Orange, excessive radiation, smoke and possibly other chemicals.
— Myeloma does not typically run in families, but there is an increased incidence in individuals with a family member with multiple myeloma.
[READ: Worst Cancer-Causing Foods.]
Signs and Symptoms
There is no cardinal sign or symptom of myeloma, so myeloma is not usually caught early, Mikhael explains. Mikhael is also the American Society of Hematology treasurer, a professor in the Applied Cancer Research and Drug Discovery Division at the Translational Genomics Research Institute and director of Myeloma Research and Consultant Hematologist at HonorHealth Research Institute.
Patients often have general symptoms that require further evaluation, like:
— Anemia
— Bone pain (particularly in the back and ribs)
— Fractures from minimal trauma (typically in the spine)
— Bleeding or bruising easily
— Fatigue
— Weakness
— Breathing difficulties
— Nausea, loss of appetite and weight loss
— Increased thirst and frequent urination
— Frequent infections and fevers
"When myeloma is very active, it creates four common issues that we call 'CRAB,'" says Dr. Daniel Landau, a board-certified oncologist in South Carolina and expert contributor for the Mesothelioma Center at Asbestos.Com.
CRAB consists of:
— C for calcium: Myeloma causes high calcium, or hypercalcemia. Myeloma pulls calcium out of bones and into the bloodstream. Some people may have no symptoms of high calcium, while others may have loss of appetite, nausea, vomiting, weakness or brain fog.
— R for renal failure: As M proteins accumulate in the urine, it can lead to kidney damage.
— A for anemia: Anemia is a lack of healthy red blood cells. As the abnormal plasma cells grow in the bone marrow, normal red-blood-cell production is disrupted. Because red blood cells normally help supply the body with oxygen, anemia can cause weakness or shortness of breath in some people. Platelets, the blood cells responsible for clotting, can also be affected, resulting in excessive bleeding.
— B for bone: Myeloma cells secrete chemicals that can destroy bone. As calcium is depleted in the bones, they become thinner, weaker and more brittle, similar to osteoporosis. Some people experience bones that break more easily, even with minimal stress, such as picking up routine household objects. Bone pain, like unexplained and worsening back pain, can also occur.
Sometimes, a lowercase "i" is added to the CRAB acronym because infection is common with multiple myeloma. Although there are more antibiotics and vaccines to treat these infections, repeated infections are still a serious threat to those with multiple myeloma. Replacement treatment with intravenous immunoglobulin can be used for patients who have low levels of antibodies in their blood.
Diagnosis
Your doctor will need to rule out other possible conditions to provide a definitive diagnosis of multiple myeloma. You may undergo several types of testing, including the following:
— Blood and urine tests. Complete blood counts measure a patient's level of red blood cells, white blood cells and plasma cells. Other blood tests are done to measure calcium and uric acid levels and assess kidney function. Abnormal results can then lead to more in-depth testing. Blood and urine tests called protein electrophoresis are used to measure M protein levels.
— Bone marrow biopsy. In this invasive test, a long needle is inserted into a bone, often a hip bone, to collect a bone marrow sample. You may receive a local anesthetic to numb the area before the biopsy. The sample is sent to a laboratory for analysis. Specialized lab tests can identify myeloma cells, their genetic abnormalities and how rapidly they're dividing.
— Imaging tests. Imaging tests, such as an X-ray, MRI, CT or PET scan, are done to pinpoint the spread of myeloma and bone problems.
Diagnosing multiple myeloma includes assigning a stage number according to its extent.
Sometimes, there is a premalignant condition, before stage 1. This is called monoclonal gammopathy of undetermined significance or MGUS. Though there are no symptoms in MGUS, the M protein can be identified in the blood. MGUS screening is not done routinely for multiple myeloma surveillance because not everyone with MGUS will develop myeloma.
Slightly more advanced than MGUS is smoldering myeloma, or indolent myeloma. Someone who has progressed to smoldering myeloma has higher levels of M cells but still no symptoms. The next stage is active myeloma.
Factors that determine whether myeloma is stage 1, stage 2 or stage 3 include:
— The amount of M protein levels in the blood or urine
— Calcium levels in the blood
— The presence of anemia
— Whether bone damage exists and how advanced it is
Stages are further classified as "A" or "B" depending on the absence or presence of significant kidney damage.
Mikhael says the International Myeloma Foundation is working on earlier detection methods. "The International Myeloma Foundation participated in a large screening study in Ireland. It's likely that we will develop a screening for myeloma like we do for breast or colon cancer."
[SEE: Questions to Ask Your Oncologist at Your First Cancer Appointment.]
Prognosis
"It is something that is not considered to be curable, even though patients live much, much longer than they used to 10 or 15 years ago," says Dr. Shaji Kumar, a professor and consultant in the division of hematology at Mayo Clinic in Rochester, Minnesota. "In fact, the older patients with no adverse disease characteristics may have their expected life expectancy with the current treatments."
Kumar adds that there are roughly 36,000 new diagnoses of multiple myeloma in the United States each year, and about 12,000 people die from multiple myeloma annually in the United States.
Survival rates for multiple myeloma vary by the stage at which it's diagnosed. Overall, the five-year survival rate is 58% according to the American Society of Clinical Oncology. For the minority of people diagnosed at an early stage, five-year survival is 79%. For people with later-stage myeloma that has spread to distant areas of the body, five-year survival is about 57%.
Not all people who have abnormal plasma cells will get myeloma. "You can detect these abnormal plasma cells and the abnormal protein they secrete, we believe, on average 20 years before myeloma comes on," Kumar explains. "However, among the majority of people in whom you detect the abnormal protein, 80% of those people will never get myeloma. Only 20% of people will progress to the point where they actually have a cancerous condition that needs treatment."
Treatment
Current treatment guidelines for multiple myeloma patients involve three phases.
These phases include:
— Initial (or induction) treatment
— Possible stem cell transplant
— Maintenance therapy
Each treatment phase is individualized depending on a patient's overall health, including any organ damage or other myeloma complications and coexisting medical conditions.
Whether a patient has previously gone through myeloma treatment and relapsed, and how they responded to that treatment, is also taken into account.
Triple or quadruple-drug regimen
Some elderly or frail individuals may only receive single-drug therapy for their induction treatment. But in many cases, people receive triple or quadruple drug therapy.
The regimen includes:
— Lenalidomide. This drug enhances the immune response and inhibits the growth of myeloma cells.
— Dexamethasone. This is a steroid used to reduce inflammation and suppress the immune system to help control myeloma. It can also ease symptoms of side effects.
— Carfilzomib. This is a proteasome inhibitor that blocks protein breakdown in myeloma cells, causing them to die.
— Daratumumab. This is used in a quadruple-drug regimen, and works by finding a protein called CD38 on myeloma cells and attaching to it. This helps the body's immune system destroy the cancer cells.
Stem cell transplant with melphalan
If your doctor determines it's safe to have a stem cell translate, you usually have initial triple or quadruple-drug therapy followed by a stem cell transplant.
The transplant is called an autologous stem cell transplant because it uses your own stem cells — there is no outside donor. Although an autologous stem cell transplant avoids the long-term complications that can occur with a transplant using donor cells (allogenic transplant), it is still a complex procedure.
The process involves the following:
— First, stem cells are removed from your bone marrow or circulating blood and stored. "Overall, it takes about a week to collect the stem cells," Kumar says.
— Then, you then receive high-dose chemotherapy such as melphalan to destroy the cancerous myeloma cells. During the high-dose chemotherapy, the acute phase, you need to be in the hospital or treated and monitored as an outpatient daily, Kumar says. As chemotherapy makes your blood counts drop, you may need to have transfusions. You're also at increased risk for infection.
— Next, your stored stem cells are reinfused into your blood, to eventually mature into healthy new blood cells. It takes about two to three weeks to complete the stem cell transplant. "For most people, it's a question of being away from home for about five to six weeks to get everything done," Kumar says.
CAR T-cell therapy
CAR T-cell therapy involves changing the genes in certain immune cells to help them fight cancer. This therapy is used in other conditions sometimes, but in multiple myeloma, they target the BCMA protein because it is found in high amounts on the surface of myeloma cells.
The therapy is performed in three phases:
— Collecting T-cells: T-cells are taken from the blood using a leukapheresis machine. The blood goes through the machine to remove the T-cells, and then the rest of the blood goes back into the body. This usually takes a few hours.
— Genetic alteration and multiplication: The T-cells are sent to a lab, where they are changed to have receptors on their surface that help them find and attach to cancer cells. The lab then makes more of these altered T-cells over several weeks.
— Infusing CAR T-cells: The individual receives chemotherapy to prepare their immune system for the CAR T-cells. Then, the new CAR T cells are put back into the blood, where they find and attack the cancer cells.
Side effects
As with transplant and high-dose chemotherapy, the initial triple or quadruple-drug therapy may cause a variety of side effects, depending on the specific medications. Side effects often include:
— Nausea, vomiting and diarrhea
— Weight gain, increased blood sugar and changes in mood or sleep due to the steroids, like dexamethasone.
— Fatigue, reduced blood count, increased risk of blood clots or nerve damage from immune-modifying drugs or proteasome inhibitors, like carfilzomib.
Managing side effects like these to help you better tolerate medications and transplant is an important part of your myeloma treatment. Once initial therapy is completed, response rates are encouraging. "Between the treatments that we have — transplant and combination therapy — between 95% and 97% of patients will respond," Kumar says.
Maintenance therapy
Typically, patients stay on a lower dose of a drug once they're in remission. Other drugs or combinations may be used.
For maintenance thearpy, the following medications are often used:
— Lenalidomide
— Bortezomib
— Ixazomib
Remission
Remission is the goal for multiple myeloma treatment. Remission means you no longer have myeloma symptoms or detectable signs of disease in your blood, urine or bone marrow. Treatment response may be complete or partial and remission can be permanent or temporary.
Some patients will experience shorter-than-average remissions, while others may stay in remission up to 10 years or even longer.
When in remission, it's important to keep up with some lifestyle changes:
— Due to the strain on the kidneys caused by multiple myeloma, your doctor may recommend a kidney diet.
— Due to the bone breakdown from multiple myeloma, you'll need to be careful to avoid lifting heavy objects.
— You may need to take supplements, Kumar says. "It's recommended that patients take calcium and vitamin D supplements to help with bone disease."
"Most of the patients we see are able to do the majority of the things that they are accustomed to with little limitations, especially once the disease is in remission," Mikhael adds.
Complications
Myeloma complications can be formidable. In addition to managing cancer, many patients contend with associated bone and kidney conditions.
Common complications include:
— Compression fractures due to weakened and brittle bones
— Kidney failure, which may require dialysis several times per week. Dialysis helps to filter the blood, removing waste, salt and excess fluid from the body and controlling blood pressure, which are essential kidney functions.
— Anemia, which may require occasional blood transfusion to restore red blood cells to the proper levels, or your doctor may recommend a medication called as erythropoietin to stimulate the bone marrow to produce more red blood cells.
Health Care Providers
As you undergo diagnosis and treatment for multiple myeloma, members of your health care team may include several of these specialists:
— Hematologist/oncologist
— Oncology nurse
— Radiologist
— Orthopedic surgeon
— Neurologist.
— Nephrologist (kidney specialist)
— Pain management specialist
— Oncology pharmacist
Dedicated myeloma centers are also useful to offer staff-wide expertise in managing myeloma and access to the latest treatments, along with specialists who can be immediately consulted when people have myeloma-related complications like spinal fractures. Research is a priority.
In some cases, participating in a clinical trial can offer you access to state-of-the art treatments awaiting approval by the FDA.
The Multiple Myeloma Research Foundation has an online search tool to locate U.S. Treatment centers with a focus on multiple myeloma.
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A Guide to Multiple Myeloma: Symptoms, Treatment and Prognosis originally appeared on usnews.Com
Update 09/11/24: This story was previously published at an earlier date and has been updated with new information.
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