Multiple myeloma is a type of blood cancer that forms in plasma cells. Plasma cells are a type of white blood cell present in the bone marrow that produces antibodies to help fight infection. In multiple myeloma, these plasma cells grow out of control and accumulate in the bone marrow, crowding out healthy blood cells. Multiple myeloma is generally considered incurable, but catching it early and starting treatment promptly can lead to longer remission periods and improved quality of life.
What is multiple myeloma?
Multiple myeloma, also known as myeloma or plasma cell myeloma, is a cancer that forms in plasma cells. Normal plasma cells are found in the bone marrow and produce antibodies that help the body fight infection. In multiple myeloma, a group of plasma cells becomes cancerous and multiplies uncontrollably. These myeloma cells produce large amounts of a single type of antibody, called monoclonal protein or M protein, that has no useful function. Large amounts of M protein in the blood and urine can lead to kidney problems. Myeloma cells also damage and weaken bones, leading to bone pain and an increased risk of fractures. Other possible symptoms include fatigue, weakness, repeated infections, nausea, thirst, weight loss, constipation, confusion, and dizziness. Multiple myeloma accounts for around 1% of all cancers and 10% of hematologic (blood) cancers. In the United States, about 32,000 new cases are diagnosed every year. Multiple myeloma becomes more common with age, and the average age at diagnosis is 69 years old. It is rare before age 40.
What causes multiple myeloma?
The exact cause of multiple myeloma is unknown. However, certain factors are associated with increased risk:
– Age – Risk increases as you get older, most cases occur in people over 65.
– Gender – Men are slightly more likely to develop myeloma than women.
– Race – Multiple myeloma is more than twice as common in African Americans as in white Americans. The reason is unclear.
– Radiation exposure – Exposure to large doses of radiation increases risk.
– Family history – Having a sibling or parent with myeloma raises your risk slightly.
– Obesity – Being overweight or obese increases risk.
– Other plasma cell disorders – Having a condition called monoclonal gammopathy of undetermined significance (MGUS) increases the risk of eventually developing multiple myeloma.
The development of myeloma is a multi-step process that requires several genetic mutations in plasma cells. These mutations allow the plasma cells to grow uncontrollably and avoid normal cell death mechanisms. It’s unclear exactly what causes these mutations, but factors like family history and radiation exposure may play a role. One theory is that repeated immune system stimulation, for example from chronic infections, can increase the likelihood of mutations accumulating in plasma cells. Over time, some plasma cells acquire enough mutations to become myeloma.
What are the stages of multiple myeloma?
Multiple myeloma is divided into different stages based on the severity of the disease. Staging helps guide treatment and prognosis. The stages are:
Stage I (early myeloma):
– Fewer than 10% plasma cells in the bone marrow
– M protein levels less than 30 g/L
– No myeloma-related organ damage or symptoms
Stage II (intermediate myeloma):
– 10-60% plasma cells in the bone marrow
– M protein levels greater than 30 g/L
– No myeloma-related organ damage or symptoms
Stage III (advanced myeloma):
– More than 60% plasma cells in the bone marrow
– M protein levels greater than 30 g/L
– Presence of myeloma-related organ damage such as bone lesions, anemia, kidney dysfunction
The definitions of stage I and II are somewhat controversial, with other staging systems using different cutoffs. In general, stage I represents early disease with lower tumor burden, stage III is advanced extensive disease, and stage II falls between the two. Prognosis and treatment approach depends strongly on the stage at diagnosis.
What are the early symptoms of multiple myeloma?
The most common early symptoms of multiple myeloma are:
– Bone pain – The most frequently reported symptom, caused by myeloma lesions weakening bone. Pain is often worse in the back or ribs.
– Fatigue – Feeling abnormally tired and weak, resulting from anemia and other effects of the cancer. Fatigue tends to worsen over time.
– Recurrent infections – Myeloma hampers the immune system, increasing susceptibility to pneumonia, urinary tract infections, and shingles.
– Numbness and tingling – Can result from spinal cord compression caused by plasma cell growth or bone lesions. Typically starts in the legs.
– Weight loss – Unexplained weight loss of 10 or more pounds over a short period of time can be an early sign.
– Bruising or bleeding easily – Platelet counts may drop, impairing blood clotting.
– High blood calcium – Calcium released from damaged bones raises calcium levels. Can cause frequent urination, thirst, and constipation.
– Kidney problems – Excess antibody proteins can damage the kidneys and lead to dehydration, confusion, and fatigue.
Keep in mind that these symptoms are common in the general population and not everyone who experiences them has myeloma. However, having one or more of these symptoms persistently with no other cause should prompt a visit to the doctor for blood and urine tests.
How is multiple myeloma diagnosed?
Diagnosing multiple myeloma requires:
– Blood and urine tests – High levels of M protein or light chains indicate myeloma. Other findings include anemia and abnormal kidney function.
– Bone marrow biopsy – Examination of a bone marrow sample shows increased plasma cells, diagnostic of myeloma. Also shows chromosome/genetic abnormalities.
– Imaging tests – X-rays, CT, MRI, and PET scans detect bone lesions and plasmacytomas (myeloma cell masses). Help determine the stage and extent of disease.
– Skeletal survey – X-ray images of the entire skeleton look for thinning bones and other bone abnormalities.
If initial tests suggest multiple myeloma, more blood/urine tests measure M protein levels and subtype, kidney function, etc. Chromosome analysis helps determine prognosis and guide treatment. Imaging studies assess bone and organ involvement. Repeating blood/urine tests over time judges the disease’s progression rate.
What is the life expectancy for multiple myeloma?
The life expectancy for multiple myeloma depends heavily on the stage at diagnosis:
– Stage I – The 5-year relative survival rate is 62%. Many patients live 10 years or longer.
– Stage II – The 5-year survival rate is 45%.
– Stage III – The 5-year survival rate is 36%. Survival beyond 5 years is less common.
Overall, the 5-year relative survival rate for myeloma from 2007-2013 was 51%. However, survival is improving with newer therapies. Patients diagnosed from 2008-2014 have a 5-year survival rate of 58%. With optimal treatment, some myeloma experts estimate typical life expectancy is 7-10 years for standard-risk patients. In higher-risk myeloma with more aggressive features, the outlook is poorer.
Prognosis is best for people diagnosed at an early smoldering stage before major symptoms develop. These patients have a 10-year survival rate of 75%. Life expectancy is greatly reduced for later-stage active myeloma. Early diagnosis and prompt treatment initiation are key to improving chances of long-term survival.
Can multiple myeloma be cured?
Unfortunately, multiple myeloma is currently considered incurable with standard treatments. While remissions are often achieved that can last for years, the disease invariably returns and requires further therapy. However, researchers are working on promising new approaches that could lead to an outright cure for some patients in the future.
The main barrier to curing myeloma is that a small number of cancerous plasma cells always seem to escape even the strongest drugs and regrow later. These residual myeloma cells may hide in the bone marrow, protected from chemotherapy. Over months to years, they multiply and cause the cancer to relapse.
Another challenge is the genetic instability of myeloma cells, which allows them to develop drug resistance by mutating further over time. The cancer cells in relapse often have different mutations and characteristics than those initially present.
Despite the lack of a cure, remission and long-term control of myeloma is possible in many patients with current treatments. Appropriate drug combinations and optimal sequencing of therapies helps delay relapses and extends life. Emerging immunotherapies like CAR T-cell therapy also offer hope by harnessing the patient’s own immune system against myeloma.
While multiple myeloma remains incurable for now, researchers are pursuing a number of promising approaches that could change the outlook, especially for patients diagnosed very early.
What is the treatment for early-stage multiple myeloma?
Treatment of early-stage myeloma aims to control the disease, alleviate symptoms, maximize remission time, and minimize side effects. Specific recommended therapies depend on a patient’s age, overall health, risk stratification, and personal preferences. Treatments for early-stage disease can include:
– Active monitoring without therapy (for smoldering myeloma)
– Corticosteroids like dexamethasone to reduce inflammation
– Targeted drugs – Proteasome inhibitors like bortezomib; immunomodulators like lenalidomide; HDAC inhibitors like panobinostat
– Chemotherapy drugs like cyclophosphamide, doxorubicin
– Stem cell transplant – Often autologous transplant with the patient’s own stem cells
– Radiation therapy for plasmacytomas and painful bone lesions
– Bisphosphonates or denosumab to strengthen bones and reduce fractures
– Plasmapheresis to reduce M proteins for kidney problems
– Pain medications, anti-nausea drugs, bisphosphonates to control symptoms
Younger, healthier patients may undergo more aggressive treatment to prevent progression, while older or frail patients may receive milder regimens to minimize toxicity. Clinical trials evaluating new myeloma drugs and immunotherapies are appropriate options for many patients. Avoiding early relapse is important to prolong survival and maintain quality of life.
What is high-dose chemotherapy with stem cell transplant for multiple myeloma?
High-dose chemotherapy along with autologous stem cell transplantation is a common and effective treatment for multiple myeloma patients. It aims to eliminate as many myeloma cells as possible to extend the remission period.
The process involves:
1. Stem cell harvest – Patient’s blood stem cells are collected from the bloodstream.
2. High-dose chemotherapy – Patient receives intravenous high doses of chemotherapy drugs like melphalan or busulfan over several days.
3. Stem cell transplant – Patient’s own harvested stem cells are returned to their bloodstream via IV where they travel to the bone marrow.
4. engraftment and recovery – Over the next few weeks, the transplanted stem cells repopulate the bone marrow and blood cell counts recover.
The high chemotherapy doses are much stronger than standard doses. This intensive treatment can destroy many stubborn myeloma cells and achieve remission when other therapies fail. After engraftment, the transplanted stem cells restore normal blood cell production.
Stem cell transplant carries significant risks of infection, bleeding, organ damage, and even treatment-related death. It has the most benefit for younger, fit patients with early-stage disease and high-risk prognostic features. Transplants are often effective at controlling myeloma for many years after diagnosis. However, they are not generally considered curative since relapse still eventually occurs.
Can multiple myeloma be cured with a stem cell transplant?
Stem cell transplantation can produce extended remission periods in multiple myeloma patients. However, it is not considered an outright cure even when done early in the course of disease. Reasons why stem cell transplant does not cure myeloma include:
– Residual myeloma – A few myeloma cells inevitably survive even the high chemotherapy doses and eventually multiply causing relapse.
– Genetic mutations – Myeloma cells develop new mutations that make them resistant to the transplant chemotherapy drugs.
– Microenvironment interactions – Bone marrow stromal cells and proteins called cytokines help protect some myeloma cells from chemotherapy.
– Clone evolution – Myeloma is very genetically heterogeneous. The dominant clones relapse originates from are different than the original clones.
While transplants cure some other blood cancers like leukemia, myeloma is a much trickier disease to eliminate permanently. Still, stem cell transplants extend the remission duration and survival substantially compared to chemotherapy alone.
For eligible patients diagnosed with early-stage myeloma and no high-risk features, undergoing an autologous transplant soon after initial therapy offers the best chance of prolonged disease control. Allogeneic transplants using donor cells also have a role in selected high-risk patients. Adding post-transplant maintenance therapy helps further delay relapse after transplants.
Research is ongoing into how to make transplants more effective and overcome myeloma’s tendency to recur. The curative potential may be improved in the future through combination with novel drugs or immunotherapy approaches.
What maintenance therapy is used after a stem cell transplant for myeloma?
Maintenance therapy in myeloma refers to treatment given after the stem cell transplant aimed at delaying disease relapse. It typically consists of lower doses of an oral drug for a prolonged period. Common choices for maintenance therapy include:
– Lenalidomide – An immunomodulatory drug that enhances the immune response against myeloma cells and disrupts tumor growth signals.
– Bortezomib – A proteasome inhibitor drug that induces myeloma cell death and inhibits cell growth pathways.
– Prednisone or dexamethasone – Corticosteroid drugs that reduce inflammation and have direct anti-myeloma effects.
Maintenance therapy is typically given until relapse or unacceptable side effects occur. Treatment is then discontinued or switched to an alternative drug. The advantages of maintenance therapy are:
– Delays relapse after transplant by around 1-2 years on average
– Extends the remission duration and improves overall survival
– Well tolerated at lower doses with manageable side effects
– Helps eradicate any residual myeloma cells and prevent regrowth
– Less costly and intensive than a second stem cell transplant
The downside is requiring daily medication and potential cumulative drug toxicities. Maintenance therapy with lenalidomide or bortezomib is now a standard recommendation for myeloma patients after transplant while they are in remission. Adding maintenance therapy after a stem cell transplant gives the best chance of prolonged disease control in early myeloma.
Can multiple myeloma relapse after a stem cell transplant?
Unfortunately, relapse after autologous stem cell transplantation is common in myeloma patients, even those who undergo transplant soon after diagnosis. About 50% of myeloma patients relapse within 2 years of transplant and 75% relapse within 5 years. The median remission duration is 3-4 years.
Reasons myeloma can relapse even after the intensive therapy of a transplant include:
– Myeloma stem cells – Rare myeloma cells resembling tissue stem cells survive transplant and repopulate the cancer.
– Microenvironment interactions – Bone marrow niche cells and proteins help protect myeloma cells from chemotherapy.
– Clonal evolution – Myeloma comprises many distinct clones that evolve over time, with new dominant clones at relapse that are resistant to the original chemotherapy.
– Residual disease – Very sensitive tests detect residual myeloma cells in most patients post-transplant, which eventually expand causing clinical relapse.
While stem cell transplants certainly help control myeloma compared to other therapies, they generally do not eliminate every last myeloma cell that can lead to recurrence. Younger, low-risk myeloma patients tend to have the longest remission lengths from transplant. Additional post-transplant maintenance therapy can extend the remission duration.
Despite the high relapse rate, autologous stem cell transplantation remains an important treatment option because it extends overall survival in myeloma patients. Relapsed myeloma can often be controlled for some time with additional therapy. Early transplant helps prolong myeloma remission and survival even if not curative.
What are the latest advances in multiple myeloma research?
Exciting progress is being made in multiple myeloma research that may lead to better long-term control or even cures for myeloma patients in the future:
– Novel targeted drugs – New proteasome inhibitors, immunomodulators, monoclonal antibodies, cell signaling inhibitors, epigenetic drugs and other therapies to improve results.
– Immunotherapy – Harnessing the immune system against myeloma through vaccines, CAR T cells, bispecific antibodies, etc. Showing promise for more sustained remissions.
– Genetic testing – Better understanding myeloma genetics allows more personalized, risk-based treatment selection.
– Preventing progression – Using very early intervention including monoclonal antibodies before major symptoms appear to prevent full myeloma development.
– Imaging improvements – Advances in PET/CT and MRI make detecting and monitoring myeloma lesions more sensitive to find residual disease earlier.
– Overcoming drug resistance – Combination approaches and new agents to target multi-drug resistant myeloma and hit different pathways.
– Targeting myeloma “stem cells” – Investigating ways to eliminate the self-renewing myeloma cells that propagate relapse.
While the multiple myeloma cure remains elusive, today’s many active new agents provide good disease control for prolonged periods. Further research breakthroughs hold hope that cure may become possible one day, especially when myeloma is caught very early before too many genetic changes accumulate.
Conclusion
Multiple myeloma remains an incurable but treatable cancer with current therapies. The outlook for patients is improving with recent advances providing more options to delay disease progression and prolong survival. Catching myeloma at the earliest stage offers the best chance for good symptom control, long remissions, and extended survival. While a true cure is not yet possible, the future looks brighter with many promising new approaches on the horizon. Increased awareness and early diagnosis along with prompt optimal treatment will help more myeloma patients live longer, fuller lives. Continued research focused on the biology of myeloma relapse brings hope that this challenging disease may eventually be curable.
